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Chemoreceptor
Chemoreceptor
Chemoreceptor
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A chemoreceptor, also known as chemosensor, is a specialized sensory receptor which transduces a chemical substance (endogenous or induced) to generate a biological signal.[1] This signal may be in the form of an action potential, if the chemoreceptor is a neuron,[2] or in the form of a neurotransmitter that can activate a nerve fiber if the chemoreceptor is a specialized cell, such as taste receptors,[3] or an internal peripheral chemoreceptor, such as the carotid bodies.[4] In physiology, a chemoreceptor detects changes in the normal environment, such as an increase in blood levels of carbon dioxide (hypercapnia) or a decrease in blood levels of oxygen (hypoxia), and transmits that information to the central nervous system which engages body responses to restore homeostasis.

In bacteria, chemoreceptors are essential in the mediation of chemotaxis.[5][6]

Cellular chemoreceptors

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In prokaryotes

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Bacteria utilize complex long helical proteins as chemoreceptors, permitting signals to travel long distances across the cell's membrane. Chemoreceptors allow bacteria to react to chemical stimuli in their environment and regulate their movement accordingly.[7] In archaea, transmembrane receptors comprise only 57% of chemoreceptors, while in bacteria the percentage rises to 87%. This is an indicator that chemoreceptors play a heightened role in the sensing of cytosolic signals in archaea.[8]

In eukaryotes

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Primary cilia, present in many types of mammalian cells, serve as cellular antennae.[9] The motile function of these cilia is lost in favour of their sensory specialization.[10]

Plant chemoreceptors

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Plants have various mechanisms to perceive danger in their environment. Plants are able to detect pathogens and microbes through surface level receptor kinases (PRK). Additionally, receptor-like proteins (RLPs) containing ligand binding receptor domains capture pathogen-associated molecular patterns (PAMPS) and damage-associated molecular patterns (DAMPS) which consequently initiates the plant's innate immunity for a defense response.[11]

Plant receptor kinases are also used for growth and hormone induction among other important biochemical processes. These reactions are triggered by a series of signaling pathways which are initiated by plant chemically sensitive receptors.[12] Plant hormone receptors can either be integrated in plant cells or situate outside the cell, in order to facilitate chemical structure and composition. There are 5 major categories of hormones that are unique to plants which once bound to the receptor, will trigger a response in target cells. These include auxin, abscisic acid, gibberellin, cytokinin, and ethylene. Once bound, hormones can induce, inhibit, or maintain function of the target response.[13]

Classes

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There are two main classes of chemoreceptor: direct and distance.[citation needed]

  • Examples of distance chemoreceptors are:
    • olfactory receptor neurons in the olfactory system: Olfaction involves the ability to detect chemicals in the gaseous state. In vertebrates, the olfactory system detects odors and pheromones in the nasal cavity. Within the olfactory system there are two anatomically distinct organs: the main olfactory epithelium (MOE) and the vomeronasal organ (VNO). It was initially thought that the MOE is responsible for the detection of odorants, while the VNO detects pheromones. The current view, however, is that both systems can detect odorants and pheromones.[14] Olfaction in invertebrates differs from olfaction in vertebrates. For example, in insects, olfactory sensilla are present on their antennae.[15]
  • Examples of direct chemoreceptors include:
    • Taste receptors in the gustatory system: The primary use of gustation as a type of chemoreception is for the detection of tasteants. Aqueous chemical compounds come into contact with chemoreceptors in the mouth, such as taste buds on the tongue, and trigger responses. These chemical compounds can either trigger an appetitive response for nutrients, or a defensive response against toxins depending on which receptors fire. Fish and crustaceans, who are constantly in an aqueous environment, use their gustatory system to identify certain chemicals in the mixture for the purpose of localization and ingestion of food.
    • Insects use contact chemoreception to recognize certain chemicals such as cuticular hydrocarbons and chemicals specific to host plants. Contact chemoreception is more commonly seen in insects but is also involved in the mating behavior of some vertebrates. The contact chemoreceptor is specific to one type of chemical.[15]

Sensory organs

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  • Olfaction: In terrestrial vertebrates, olfaction occurs in the nose. Volatile chemical stimuli enter the nose and eventually reach the olfactory epithelium which houses the chemoreceptor cells known as olfactory sensory neurons often referred to as OSNs. Embedded in the olfactory epithelium are three types of cells: supporting cells, basal cells, and OSNs. While all three types of cells are integral to normal function of the epithelium, only OSN serve as receptor cells, i.e. responding to the chemicals and generating an action potential that travels down the olfactory nerve to reach the brain.[2] In insects, antennae act as distance chemoreceptors. For example, antennae on moths are made up of long feathery hairs that increase sensory surface area. Each long hair from the main antenna also has smaller sensilla that are used for volatile olfaction.[16] Since moths are mainly nocturnal animals, the development of greater olfaction aids them in navigating the night.
  • Gustation: In many terrestrial vertebrates, the tongue serves as the primary gustatory sensory organ. As a muscle located in the mouth, it acts to manipulate and discern the composition of food in the initial stages of digestion. The tongue is rich in vasculature, allowing the chemoreceptors located on the top surface of the organ to transmit sensory information to the brain. Salivary glands in the mouth allow for molecules to reach chemoreceptors in an aqueous solution. The chemoreceptors of the tongue fall into two distinct superfamilies of G protein-coupled receptors. GPCR's are intramembrane proteins than bind to an extracellular ligand- in this case chemicals from food- and begin a diverse array of signaling cascades that can result in an action potential registering as input in an organism's brain. Large quantities of chemoreceptors with discrete ligand-binding domains provide for the five basic tastes: sour, salty, bitter, sweet, and savory. The salty and sour tastes work directly through the ion channels, the sweet and bitter taste work through G protein-coupled receptors, and the savory sensation is activated by glutamate.[citation needed]Gustatory chemosensors are not just present on the tongue but also on different cells of the gut epithelium where they communicates the sensory information to several effector systems involved in the regulation of appetite, immune responses, and gastrointestinal motility.[17]
  • Contact Chemoreception: Contact chemoreception is dependent on the physical contact of the receptor with the stimulus. The receptors are short hairs or cones that have a single pore at, or close to the tip of the projection. They are known as uniporous receptors. Some receptors are flexible, while others are rigid and do not bend with contact. They are mostly found in the mouthparts, but can also occur on the antennae or legs of some insects. There is a collection of dendrites located near the pores of the receptors, yet the distribution of these dendrites changes depending on the organism being examined. The method of transduction of the signal from the dendrites differs depending on the organism and the chemical it is responding to.

When inputs from the environment are significant to the survival of the organism, the input must be detected. As all life processes are ultimately based on chemistry it is natural that detection and passing on of the external input will involve chemical events. The chemistry of the environment is, of course, relevant to survival, and detection of chemical input from the outside may well articulate directly with cell chemicals.[citation needed]

Chemoreception is important for the detection of food, habitat, conspecifics including mates, and predators. For example, the emissions of a predator's food source, such as odors or pheromones, may be in the air or on a surface where the food source has been. Cells in the head, usually the air passages or mouth, have chemical receptors on their surface that change when in contact with the emissions. It passes in either chemical or electrochemical form to the central processor, the brain or spinal cord. The resulting output from the CNS (central nervous system) makes body actions that will engage the food and enhance survival.[citation needed]

Physiology

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  • Carotid bodies and aortic bodies detect changes primarily in pCO2 and H+ ion concentration. They also sense decrease in partial pressure of O2, but to a lesser degree than for pCO2 and H+ ion concentration.
  • The chemoreceptor trigger zone is an area of the medulla in the brain that receives inputs from blood-borne drugs or hormones, and communicates with the vomiting center (area postrema) to induce vomiting.[citation needed]
  • Primary cilia play important roles in chemosensation. In adult tissues, these cilia regulate cell proliferation in response to external stimuli, such as tissue damage. In humans, improper functioning of primary cilia is associated with important diseases known as ciliopathies.[9]

Control of breathing

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Particular chemoreceptors, called ASICs, detect the levels of carbon dioxide in the blood. To do this, they monitor the concentration of hydrogen ions in the blood, which decrease the pH of the blood. This can be a direct consequence of an increase in carbon dioxide concentration, because aqueous carbon dioxide in the presence of carbonic anhydrase reacts to form a proton and a bicarbonate ion.[citation needed]

The response is that the respiratory centre (in the medulla), sends nervous impulses to the external intercostal muscles and the diaphragm, via the intercostal nerve and the phrenic nerve, respectively, to increase breathing rate and the volume of the lungs during inhalation.

Chemoreceptors that regulate the depth and rhythm of breathing are broken down into two categories.[citation needed]

  • central chemoreceptors are located on the ventrolateral surface of medulla oblongata and detect changes in pH of cerebrospinal fluid. They have also been shown experimentally to respond to hypercapnic hypoxia (elevated CO2, decreased O2), and eventually desensitize, partly due to redistribution of bicarbonate out of the cerebrospinal fluid (CSF) and increased renal excretion of bicarbonate.[18] These are sensitive to pH and CO2.[19]
  • peripheral chemoreceptors: consists of aortic and carotid bodies. Aortic body detects changes in blood oxygen and carbon dioxide, but not pH, while carotid body detects all three. They do not desensitize. Their effect on breathing rate is less than that of the central chemoreceptors.[citation needed]

Heart rate

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The response to stimulation of chemoreceptors on the heart rate is complicated. Chemoreceptors in the heart or nearby large arteries, as well as chemoreceptors in the lungs, can affect heart rate. Activation of these peripheral chemoreceptors from sensing decreased O2, increased CO2 and a decreased pH is relayed to cardiac centers by the vagus and glossopharyngeal nerves to the [medulla oblongata|medulla] of the brainstem. This increases the sympathetic nervous stimulation on the heart and a corresponding increase in heart rate and contractility in most cases.[20] These factors include activation of stretch receptors due to increased ventilation and the release of circulating catecholamines.

However, if respiratory activity is arrested (e.g. in a patient with a high cervical spinal cord injury), then the primary cardiac reflex to transient hypercapnia and hypoxia is a profound bradycardia and coronary vasodilation through vagal stimulation and systemic vasoconstriction by sympathetic stimulation.[21] In normal cases, if there is reflexive increase in respiratory activity in response to chemoreceptor activation, the increased sympathetic activity on the cardiovascular system would act to increase heart rate and contractility.

See also

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List of distinct cell types in the adult human body

References

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Revisions and contributorsEdit on WikipediaRead on Wikipedia

Chemoreceptor

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A chemoreceptor is a specialized sensory receptor cell or structure that detects specific chemical substances in the internal or external environment and converts these chemical signals into electrical impulses transmitted to the . In vertebrates, chemoreceptors are broadly categorized into external types, which mediate senses like and smell, and internal (visceral) types, which monitor blood chemistry to regulate vital functions such as respiration and cardiovascular activity. External chemoreceptors include gustatory receptors in on the and oropharynx, which respond to molecules like sugars (sweet), (umami), salts (salty), acids (sour), and bitter compounds via G-protein-coupled receptors or channels. Olfactory receptors in the nasal detect volatile odorants binding to G-protein-coupled receptors on cilia, allowing discrimination of thousands of scents for environmental navigation and social behaviors. Internal chemoreceptors, primarily peripheral and central, play crucial roles in by sensing gases and . Peripheral chemoreceptors are located in the carotid bodies near the carotid artery bifurcation and aortic bodies along the ; these small, highly vascularized structures (e.g., 2–3 mm in humans with blood flow of 1.0–2.0 L/min/100 g) contain type I glomus cells that detect hypoxia (low O₂, with sensitivity increasing exponentially below 40 mmHg PO₂), (high CO₂), and via mechanisms involving K⁺ TASK channels, acid-sensing ion channels, and release like ATP and . They contribute 20–30% to the ventilatory response to CO₂/H⁺ and trigger reflexes increasing breathing rate, , and during , with chronic hypoxia enhancing their sensitivity. Central chemoreceptors, situated in the of the , primarily sense changes in and CO₂ (via H⁺ diffusion), driving the majority of the hypercapnic ventilatory response to maintain acid-base balance. Beyond sensory and respiratory functions, chemoreceptors influence other systems; for instance, the in the of the medulla detects blood-borne toxins to induce , protecting against . Dysregulation of chemoreceptors is implicated in conditions like , , and , where heightened peripheral sensitivity exacerbates sympathetic overactivity and ventilatory instability. Overall, these receptors ensure adaptive responses to chemical cues, underscoring their evolutionary conservation across for .

Overview and Classification

Definition and General Function

Chemoreceptors are specialized proteins or cells that detect chemical changes in the surrounding environment or internal body fluids, transducing these stimuli into electrical or biochemical signals to elicit appropriate physiological responses. These sensory structures bind specific ligands, such as ions, gases like CO₂, or metabolites like glucose, initiating pathways that enable organisms to sense and react to chemical gradients. The general mechanism of chemoreceptors involves binding to receptor sites on transmembrane proteins, which triggers conformational changes and activates downstream signaling. This often occurs through two main receptor classes: G-protein coupled receptors (GPCRs), which engage heterotrimeric G proteins to modulate second messengers; ion channels, which directly permit ion flux. For instance, in metabotropic pathways common to many eukaryotic chemoreceptors, binding activates via G proteins, leading to cyclic AMP (cAMP) production that opens cyclic nucleotide-gated channels or activates for signal amplification. Chemoreceptors represent ancient sensory mechanisms conserved across all kingdoms of , from prokaryotes to eukaryotes, facilitating essential processes like in , nutrient in animals, and environmental adaptation in diverse organisms. Their evolutionary persistence underscores their fundamental role in survival, with both ionotropic and metabotropic forms tracing back to early cellular . A key distinction exists between ionotropic and metabotropic chemoreceptors, reflecting differences in speed and integration. Ionotropic chemoreceptors function as ligand-gated ion channels, directly coupling ligand binding to ion permeation (e.g., Na⁺ or Ca²⁺ influx), resulting in rapid electrical responses within milliseconds suitable for detecting transient chemical plumes. Metabotropic chemoreceptors, conversely, indirectly transduce signals through enzymatic cascades, such as GPCR-mediated cAMP elevation that sensitizes downstream effectors, allowing for slower but more tunable and amplified responses over tens to hundreds of milliseconds. This dichotomy enables versatile chemical sensing tailored to ecological demands.

Types and Classes

Chemoreceptors are primarily classified into external and internal types based on their location and function. External chemoreceptors, also known as sensory chemoreceptors, detect chemical stimuli from the external environment and are involved in senses such as olfaction and gustation. In contrast, internal chemoreceptors, or visceral chemoreceptors, monitor the internal chemical composition of the body, with peripheral chemoreceptors located in structures like the carotid and aortic bodies to detect changes in blood oxygen, , and levels, while central chemoreceptors in the respond primarily to and CO2 concentrations. Classification by organism highlights the diversity across prokaryotes and eukaryotes, reflecting evolutionary divergence. In prokaryotes, such as , chemoreceptors mediate , enabling directed movement toward favorable conditions or away from harmful ones, as seen in coli's response to environmental gradients. Eukaryotic chemoreceptors, prevalent in and , have evolved distinct forms; animal chemoreceptors often belong to the (GPCR) superfamily for sensory detection, while plant chemoreceptors include specialized receptors for volatile compounds and nutrients. This divergence likely occurred early in evolutionary history, with prokaryotic systems relying on simpler transmembrane proteins and eukaryotic ones incorporating more complex signaling cascades adapted to multicellularity. Chemoreceptors can also be categorized by the type of stimulus they detect, providing a framework for their sensory specificity. Those responsive to chemoattractants and repellents guide or behavior toward nutrients or away from toxins, as in bacterial navigation through chemical gradients. and sensors maintain acid-base balance and electrolyte , detecting fluctuations in concentration or specific ions like sodium. detectors ensure metabolic regulation by monitoring circulating substrates. Emerging classes of chemoreceptors include orphan receptors, which are identified through genomic sequencing but lack known ligands, complicating their functional annotation and representing a significant portion of predicted chemosensory proteins in various organisms. Additionally, atypical chemoreceptor arrays have been observed in certain , such as spirochetes, where structural studies reveal non-hexagonal arrangements that adapt to high , diverging from the canonical polar arrays in model organisms like E. coli.

Cellular Chemoreceptors

In Prokaryotes

In prokaryotes, chemoreceptors primarily consist of methyl-accepting chemotaxis proteins (MCPs), which are the predominant sensory receptors in and responsible for detecting environmental chemical gradients and mediating . These receptors are integral membrane proteins that function as homodimers, each featuring an N-terminal periplasmic ligand-binding domain, two transmembrane helices, and a C-terminal cytoplasmic signaling domain. MCP dimers assemble into trimers of dimers, which further organize into extended arrays at the polar regions of the , enhancing signal amplification and sensitivity to subtle concentration changes. The signaling mechanism begins with ligand binding to the periplasmic domain of an MCP, inducing a conformational change that propagates through the transmembrane helices to the cytoplasmic domain. This modulates the autophosphorylation activity of the associated CheA histidine kinase, which is coupled to the receptor cluster via the adaptor protein CheW; attractant binding inhibits CheA autophosphorylation, reducing phosphate transfer to the response regulator CheY, thereby promoting counterclockwise flagellar rotation for smooth swimming toward the stimulus. In contrast, repellent binding or ligand unbinding activates CheA, leading to CheY phosphorylation and clockwise flagellar rotation, resulting in tumbling and random reorientation. These dynamics enable directed motility, with receptor clusters acting as cooperative units to integrate multiple signals. Adaptation to persistent stimuli occurs through reversible covalent modification of the cytoplasmic domain, where specific glutamate residues on MCPs are methylated by the CheR methyltransferase to restore signaling activity, or demethylated by the CheB methylesterase (itself activated by CheA ) to desensitize the receptor. This feedback loop ensures precise temporal sensing of concentration changes over a wide , preventing saturation and allowing sustained responsiveness. Structural studies using cryo-electron microscopy (cryo-EM) from 2014 to 2023 have refined the understanding of these arrays, confirming the trimer-of-dimers as the core organizational unit within the and revealing how CheA and CheW form alternating rings that network the receptors for efficient . A 2020 cryo-EM analysis further identified atypical array configurations in bacteria with high membrane curvature, such as those in prosthecate structures, where receptors adopt a more disordered, polar arrangement to accommodate geometric constraints while maintaining functionality. In Escherichia coli, representative MCPs include the receptor, which binds L-aspartate (and maltose via a periplasmic binding protein), and the Tsr receptor, specific for L-serine, both contributing to nutrient-seeking . Beyond chemotaxis, prokaryotic chemoreceptors play key roles in biofilm formation by directing bacterial migration to optimal attachment sites on surfaces, as seen in Pseudomonas species where MCP-mediated signaling regulates cyclic di-GMP levels to initiate sessile communities. In pathogenesis, these receptors facilitate host colonization; for instance, in Helicobacter pylori, chemoreceptors like TlpA sense host-derived signals to promote biofilm persistence and tissue invasion, enhancing virulence.

In Eukaryotes

In eukaryotic cells, chemoreceptors play a central role in detecting extracellular chemical signals, such as ligands, nutrients, and pheromones, to initiate adaptive responses that bridge cellular signaling with organismal . These receptors exhibit greater structural and functional diversity compared to prokaryotic counterparts, often involving complex cascades that amplify signals through second messengers and regulatory mechanisms. Unlike simpler bacterial systems that rely on direct activation, eukaryotic chemoreceptors frequently employ heterotrimeric G proteins or domains to transduce signals, enabling fine-tuned regulation of processes like , , and . Major families of eukaryotic chemoreceptors include G protein-coupled receptors (GPCRs), which constitute the largest class and detect a wide array of ligands through seven-transmembrane domains. For instance, rhodopsin-like GPCRs (Class A) bind small molecules or peptides to initiate sensory or metabolic responses. Receptor tyrosine kinases (RTKs), another key family, feature extracellular ligand-binding domains linked to intracellular kinase activity; the insulin receptor exemplifies this by sensing glucose levels via insulin binding, which autophosphorylates tyrosine residues to propagate signals. Ligand-gated ion channels, such as transient receptor potential (TRP) channels, directly permit ion flux upon chemical binding, contributing to rapid chemosensory transduction in various cell types. Signaling through these chemoreceptors typically involves G-protein activation for GPCRs, where binding promotes GDP-GTP exchange on the Gα subunit, dissociating it from Gβγ to modulate effectors like (producing cAMP) or (generating IP3 and diacylglycerol). This leads to downstream effects such as calcium mobilization or activation. Desensitization occurs via by G protein-coupled receptor kinases (GRKs), followed by β-arrestin recruitment, which uncouples the receptor from G proteins and promotes internalization. RTKs signal through cascades activating pathways like PI3K-Akt for metabolic , while TRP channels trigger and calcium entry. Chemoreceptors localize primarily to the plasma membrane for extracellular sensing but also function intracellularly, such as mitochondrial O2 sensors that monitor oxygen levels via (ROS) production from complex I inhibition during hypoxia, linking energy status to cellular responses. In , pheromone receptors (GPCRs like Ste2) detect factors, activating a MAPK cascade through Ste5 scaffold-mediated of Fus3, culminating in for cell cycle arrest and formation. In mammals, GLP-1 receptors in pancreatic β-cells sense hormones post-nutrient intake, enhancing glucose-dependent insulin secretion via cAMP elevation and PKA activation.

Chemoreceptors in Plants

Molecular Mechanisms

Plant chemoreceptors encompass a diverse array of receptor types specialized for detecting hormones, carbohydrates, and other chemical cues, including , kinases, and GPCR-like proteins. , particularly lectin receptor-like kinases (LecRLKs), serve as receptors that bind specific glycan structures on the cell surface, facilitating the detection of microbial or endogenous signals. These proteins are anchored to the plasma via transmembrane domains and play roles in immune recognition and developmental signaling. kinase receptors, such as the ethylene receptor ETR1 in , feature a modular structure with an N-terminal ethylene-binding domain comprising hydrophobic transmembrane helices and extracellular loops for ligand interaction. Similarly, receptors like AHK4 (also known as CRE1) possess a CHASE (cyclase/ kinase-associated sensory module) domain in their extracellular region, which selectively binds ligands. GPCR-like proteins, including GTG1 and GTG2, exhibit seven-transmembrane topologies akin to animal GPCRs and function as direct ABA receptors, coupling ligand binding to heterotrimeric G-protein activation in responses. These receptors often operate through two-component signaling systems, where binding in the extracellular domain induces autophosphorylation of a residue in the intracellular domain, followed by phosphate transfer to a response regulator that modulates downstream targets. For instance, ETR1 and related subfamily I receptors form dimers stabilized by their domains, enabling signal relay in the absence of traditional output modules. Structural studies have revealed critical features, such as an aspartate residue in ETR1's that coordinates as a cofactor for high-affinity binding, ensuring specificity at low concentrations. In cytokinin perception, the CHASE domain's -binding pocket accommodates the isoprenoid side chain of , triggering activation and phosphorelay to type-A response regulators that repress or activate . GPCR-like ABA receptors, upon engagement, promote GDP-GTP exchange on the Gα subunit, initiating cascades that enhance activity and gene transcription for stress adaptation. Key signaling pathways downstream of these chemoreceptors integrate chemical perception with rapid cellular responses. In ethylene signaling, ligand binding to ETR1 inhibits the associated Raf-like kinase CTR1, which otherwise phosphorylates EIN2 at multiple sites to mark it for degradation; ethylene perception thus stabilizes EIN2, leading to proteolytic cleavage and nuclear translocation of its C-terminal domain, where it activates EIN3/EIL1 transcription factors to induce ethylene-responsive genes involved in and . Wound responses involve chemoreceptor-mediated calcium influx, where recognition of damage-associated molecular patterns by receptors like LecRLKs or glutamate receptor-like channels (GLRs) triggers rapid Ca²⁺ entry through plasma membrane channels, propagating systemic signals via Ca²⁺ waves that coordinate defense and biosynthesis. Recent structural and functional insights have advanced understanding of chemoreceptor specificity and diversity. structures of the receptor AHK4's sensor domain, resolved in the early , demonstrated how subtle variations in the binding pocket confer selectivity for active cytokinins over inactive isomers, highlighting evolutionary adaptations in perception. For (VOC) detection, emerging evidence points to receptors like KAI2, a α/β-hydrolase fold protein, which senses -like VOCs emitted by neighboring , activating karrikin and strigolactone signaling pathways to modulate growth and defense without requiring plasma membrane localization. These findings underscore the role of plant chemoreceptors in integrating airborne chemical cues for interplant communication.

Physiological Roles

Plant chemoreceptors, particularly those responsive to , mediate chemotropism by directing and shoot growth toward nutrient-rich environments through the establishment of auxin gradients that influence cell elongation and division. receptors, such as the TIR1/AFB family proteins, perceive (IAA) and trigger asymmetric distribution, enabling roots to grow toward beneficial chemical cues like sugars or in the . This process enhances acquisition, as demonstrated in studies where auxin signaling mutants exhibit impaired bending toward nutrient patches. In plant defense, jasmonate receptors, including the COI1-JAZ co-receptor complex, detect and its derivatives to activate responses against , such as the upregulation of compounds and reinforcement of cell walls. Similarly, isoflavone-related signaling pathways contribute to resistance by inducing phytoalexin production, with metabolism triggered in response to microbial elicitors to inhibit fungal growth. Volatile signaling mediated by further aids defense by promoting the emission of herbivore-induced plant volatiles (HIPVs), which attract natural enemies of herbivores, thereby reducing herbivory pressure on the . Chemoreceptors involved in stress adaptation include abscisic acid (ABA) receptors of the PYR/PYL/RCAR family, which sense ABA accumulation during to initiate stomatal closure, minimizing transpirational water loss while maintaining . For instance, the receptor PYL9 enhances by promoting rapid responses, leading to reduced wilting in water-limited conditions. Nitrate sensors, such as the dual-function transporter NRT1.1, detect levels to modulate root architecture, stimulating proliferation in nitrate-rich zones to optimize uptake. Representative examples illustrate these roles: in , detection of via signaling pathways regulates floral scent emission, coordinating volatile release to attract pollinators during receptive periods. In , NOD factor receptors like NFR1 and NFR5 perceive lipochitooligosaccharide signals from , initiating symbiotic signaling that promotes nodule formation for . These mechanisms collectively enable plants to adapt to environmental challenges through precise chemosensory integration.

Sensory Chemoreceptors

Olfactory Receptors

Olfactory receptors are specialized chemoreceptors located in the of the , primarily responsible for detecting volatile odorant molecules in the air and initiating the in vertebrates. These receptors enable the discrimination of thousands of s through a highly organized system of s. In humans, the olfactory receptor constitutes the largest multigene family, comprising approximately 400 functional genes that encode G protein-coupled receptors (GPCRs). Each olfactory expresses only one olfactory receptor gene, and neurons expressing the same receptor converge their axons onto one or two specific glomeruli in the , forming a that facilitates initial odor processing. Structurally, olfactory receptors belong to the class A GPCR superfamily, featuring seven transmembrane α-helices, an extracellular N-terminus, and an intracellular C-terminus. Conserved motifs across the family include sequences such as DRYVAIC at the end of transmembrane helix III and a tyrosine in helix VII, which are crucial for ligand binding and signal transduction. This structure allows odorants—small, hydrophobic molecules—to bind within a pocket formed by the transmembrane helices, triggering conformational changes that activate intracellular signaling. The discovery of this large family of receptors was pivotal, revealing a molecular basis for odor recognition through a vast repertoire tuned to broad classes of odorants. Upon odorant binding, the receptor activates the subunit Gαolf (a variant of Gs), which stimulates type III to produce cyclic AMP (cAMP). The elevated cAMP levels open cyclic nucleotide-gated (CNG) cation channels, primarily composed of CNGA2 and CNGA4 subunits, allowing influx of Na⁺ and Ca²⁺ ions that depolarize the and generate action potentials. This cAMP-mediated pathway is the primary transduction mechanism in mammalian olfaction, distinguishing it from other sensory GPCRs by its reliance on Golf and rapid amplification. Calcium influx also activates chloride channels, further amplifying the signal through Cl⁻ efflux. Olfactory coding relies on a combinatorial strategy, where individual odorants activate multiple receptor types, and each receptor responds to multiple odorants, creating unique patterns of glomerular activation in the . This distributed code allows for the encoding of identity, intensity, and quality through the relative activation of receptor subsets. For pheromones, detection often involves the in many animals, where two distinct receptor families—V1Rs (tuned to pheromones) and V2Rs (for pheromones)—mediate social and reproductive behaviors via separate signaling pathways, though humans lack a functional . Recent structural advances, including cryo-EM determinations of human olfactory receptors, have illuminated recognition at atomic resolution. For instance, the 2.9 Å of OR51E2 bound to the short-chain propionate reveals an occluded binding where the forms bonds with residues like Arg262 and engages in hydrophobic interactions, inducing conformational shifts in extracellular loop 3 to facilitate coupling. These insights highlight how tight packing in the orthosteric site dictates selectivity for odorants and provide a framework for understanding the broader OR family's diversity. Additionally, olfactory receptors play roles in disease; SARS-CoV-2 infection downregulates genes for receptors like OR51E1 and OR7D4 through of supporting sustentacular cells, contributing to observed in up to 80% of cases, with recovery often occurring within months via regeneration of sensory neurons.

Gustatory Receptors

Gustatory receptors are specialized chemoreceptors located primarily in the of the oral cavity in vertebrates, enabling the detection of soluble chemical stimuli to facilitate perception. These receptors mediate the five basic modalities—sweet, , bitter, sour, and salty—by converting chemical binding into neural signals that inform feeding decisions and avoid toxins. The primary receptor types include the T1R family for and tastes, which function as heterodimers: T1R2/T1R3 detects sugars for taste, while T1R1/T1R3 recognizes like glutamate for . Bitter taste is mediated by approximately 25 T2R receptors in humans, which are G protein-coupled receptors (GPCRs) tuned to a diverse array of bitter compounds. Salty taste involves the (ENaC), an that allows sodium ion influx in response to salt concentrations. Sour taste is mediated by OTOP1, a proton-selective expressed in type III taste cells (marked by PKD2L1), where protons (H⁺) contribute to transduction by entering the cell and influencing . Mechanistically, T1R and T2R receptors activate the G protein gustducin upon ligand binding, which dissociates into subunits that stimulate phospholipase C β2 (PLCβ2); this leads to the production of inositol trisphosphate (IP3), triggering intracellular calcium release and subsequent depolarization. For sour detection, acid-induced H⁺ entry through OTOP1 depolarizes the cell, with additional contributions from pH changes blocking inwardly rectifying potassium channels (e.g., Kir2.1). ENaC-mediated salty taste relies on direct Na⁺ permeation through the channel, generating a depolarizing current without G protein involvement. In taste buds, gustatory receptors are housed within specialized epithelial cells, primarily type II cells, which express T1R and T2R receptors for sweet, , and bitter detection; these cells release ATP as a via the CALHM1/CALHM3 channel to communicate with afferent in a non-vesicular manner. Type III cells, marked by PKD2L1, handle sour transduction and employ synaptic vesicles containing serotonin for transmission, while ENaC is distributed across multiple cell types for salt sensing. This organization allows for parallel processing of taste qualities within clustered on the and . Beyond sensory perception, gustatory receptors contribute to physiological , such as sensing in the gut and , where T1R activation promotes insulin release in response to glucose or . These receptors exhibit evolutionary conservation across mammals, with T1R and T2R orthologs maintaining core functions in discrimination despite species-specific adaptations in specificity.

Internal Chemoreceptors

Central Chemoreceptors

Central chemoreceptors are specialized neurons and glial cells located primarily within the that detect changes in brain interstitial fluid and CO₂ levels to regulate and maintain acid-base . Key sites include the retrotrapezoid nucleus (RTN), situated in the ventral medulla near the facial nucleus, and the medullary raphe, a midline structure encompassing serotonergic neurons in regions such as the raphe pallidus and obscurus. These locations house both neuronal types, such as Phox₂b-expressing neurons in the RTN and serotonergic neurons in the raphe, and glial types, including in the ventral medullary surface and RTN that modulate neuronal activity through signaling molecules like ATP. The primary mechanism involves CO₂ diffusing across the blood-brain barrier into the interstitial fluid and , where it hydrates to form , leading to intracellular and extracellular acidification. This pH drop activates acid-sensitive ion channels, including acid-sensing ion channels () such as ASIC1 expressed in RTN neurons and TASK channels (e.g., TASK-1, TASK-2, TASK-3), which are pH-sensitive two-pore domain K⁺ channels that inhibit outward K⁺ currents upon acidification, depolarizing neurons and increasing firing rates. In glial cells, acidification triggers K⁺ channel (e.g., Kir4.1/Kir5.1) and ATP release via connexin 26, which indirectly stimulates nearby neurons through purinergic receptors. Other sensors like GPR4 in RTN neurons contribute by coupling proton detection to intracellular signaling pathways that enhance respiratory output. Definitive identification of central chemoreceptors relies on established experimental criteria, including direct modulation of cell activity by CO₂/H⁺, correlation of cell firing with ventilatory changes , blunting of the hypercapnic ventilatory response upon cell inhibition, opposite effects on respiration from cell activation versus inhibition, and impairment of the response when molecular sensing mechanisms are disrupted. These criteria, proposed in a 2023 review, confirm the RTN neurons and medullary raphe serotonergic neurons as primary candidates, with glial contributions playing a supportive role. Proximity to and projections to respiratory centers like the further support their chemosensory function. Central chemoreceptors provide approximately 70% of the ventilatory drive in response to , integrating signals to fine-tune breathing under varying conditions. During , they sustain CO₂ sensitivity to prevent , though overall responsiveness may attenuate compared to . In exercise-induced , they contribute by detecting any brain pH shifts from metabolic CO₂ production, independent of direct arterial changes, helping match ventilation to increased demand.00676-5)

Peripheral Chemoreceptors

Peripheral chemoreceptors are specialized sensory structures located outside the that detect changes in blood gas levels, primarily arterial oxygen (O₂), (CO₂), and pH, to initiate rapid physiological adjustments such as increased ventilation and sympathetic . These receptors are predominantly found in the carotid bodies, paired chemosensory organs situated at the bifurcation of the common carotid arteries, and to a lesser extent in the aortic bodies near the . The carotid bodies are highly vascularized and innervated by the , a branch of the , which transmits sensory signals to the . Unlike central chemoreceptors, peripheral ones are particularly sensitive to hypoxia, playing a critical role in the acute hypoxic ventilatory response. The core sensory elements of the carotid body are type I glomus cells, also known as chief cells, which are neural crest-derived and densely packed within clusters surrounded by type II sustentacular cells and fenestrated capillaries. These glomus cells express oxygen-sensitive (K⁺) channels, including TASK (TWIK-related acid-sensitive K⁺) channels and large-conductance calcium-activated K⁺ (, which maintain the resting under normoxic conditions. TASK channels, specifically TASK-1 and TASK-3 isoforms, contribute to a background K⁺ conductance that is inhibited by low O₂, while integrate intracellular with O₂ sensitivity. The aortic bodies share similar cellular architecture but exhibit lower sensitivity and density compared to the carotid bodies. The primary mechanism of hypoxic sensing in glomus cells involves the inhibition of these O₂-sensitive K⁺ channels by low arterial PO₂, leading to reduced K⁺ efflux, membrane , and subsequent activation of voltage-gated calcium (Ca²⁺) channels. This Ca²⁺ influx triggers the release of excitatory neurotransmitters, such as (ATP) and (ACh), from the glomus cells onto afferent nerve endings, generating action potentials that propagate to the . ATP acts primarily via P2X purinergic receptors on sensory afferents, while ACh contributes through nicotinic receptors, amplifying the chemosensory signal. This process occurs rapidly, within seconds of O₂ decline, ensuring precise detection of arterial . Hypercapnia (elevated CO₂) and enhance the hypoxic response in peripheral chemoreceptors by further inhibiting TASK channels, which are pH-sensitive, thereby potentiating and release in . In chronic hypoxia, such as during prolonged high-altitude exposure, the undergoes structural remodeling, including , increased vascularization, and proliferation of cells, which heightens chemosensitivity to sustain ventilatory . This involves hypoxia-inducible factor 1α (HIF-1α) upregulation in , promoting for and metabolic adjustments. Pathologically, augmented peripheral chemoreceptor activity contributes to conditions like , where hyperactivity drives excessive sympathetic outflow, as evidenced in models of and .

Physiological Functions

In Respiration

Chemoreceptors play a pivotal role in regulating respiration by integrating central and peripheral inputs to adjust breathing rate and depth in response to changes in gases. The overall ventilatory response to and hypoxia is primarily driven by central chemoreceptors, which account for approximately 70% of the response to CO₂/H⁺ changes, while peripheral chemoreceptors contribute the remaining 30%. This combined drive ensures precise control of , with the Hering-Breuer reflex providing additional modulation by activating pulmonary stretch receptors during lung inflation to inhibit inspiration and prevent overdistension, thereby fine-tuning and respiratory rhythm in coordination with chemoreceptor signals. The hypercapnic drive, mediated largely by central chemoreceptors sensitive to increases in arterial of CO₂ (PaCO₂), results in a linear increase in . In healthy individuals, ventilation rises by an average of 2-3 L/min for every 1 mmHg increase in PaCO₂ above baseline levels, maintaining acid-base and preventing . This response is rapid and proportional, reflecting the brain's direct detection of cerebrospinal pH changes induced by CO₂ diffusion. In contrast, the hypoxic drive from peripheral chemoreceptors exhibits a nonlinear response, becoming more pronounced at lower arterial oxygen levels (PaO₂ below 60 mmHg), where ventilation increases exponentially to compensate for . This mechanism is particularly critical in patients with (COPD), who often rely heavily on hypoxic drive due to blunted hypercapnic sensitivity; supplemental can suppress this drive, potentially leading to and CO₂ retention. Chemoreceptor interactions further enhance ventilatory control during physiological challenges, such as exercise, where central and peripheral inputs synergize with muscle reflexes to amplify the hyperpneic response beyond what either alone could achieve, ensuring oxygen delivery matches metabolic demand. Developmentally, neonatal chemoreceptor sensitivity undergoes significant maturation; preterm infants show a higher peripheral contribution to ventilatory drive (up to 85% at 32 weeks postmenstrual age), which decreases with age as central mechanisms strengthen, influencing stability in early life.

In Cardiovascular Regulation

Chemoreceptors contribute to cardiovascular regulation by detecting alterations in gases and , eliciting responses that adjust , , and vascular tone to maintain . Peripheral chemoreceptors, primarily in the , sense hypoxia and , while central chemoreceptors monitor changes influenced by CO₂ levels. These sensory inputs integrate in the to modulate autonomic outflow, ensuring adaptive cardiovascular adjustments during physiological stress such as exercise or altitude exposure. The carotid body serves as a key site for reflex arcs in cardiovascular control. Activation of carotid body chemoreceptors by reduced arterial oxygen or increased CO₂/pH acidity stimulates type I glomus cells, which release neurotransmitters like ATP and acetylcholine to excite afferent fibers in the carotid sinus nerve, a branch of the glossopharyngeal nerve (cranial nerve IX). These signals project to the nucleus tractus solitarius in the medulla, triggering sympathetic outflow from the rostral ventrolateral medulla. This results in increased heart rate (tachycardia) and vasoconstriction in peripheral vascular beds, such as skeletal muscle, splanchnic, and renal regions, thereby elevating blood pressure to enhance oxygen delivery. In acute hypoxia, this chemoreflex latency is approximately 0.2–0.8 seconds, with peak effects within 1–5 seconds, underscoring its rapid protective role. Local oxygen-sensing mechanisms in the pulmonary vasculature, functioning as intrinsic oxygen sensors within and endothelial cells of pulmonary arteries, mediate hypoxic pulmonary (HPV). When alveolar pO₂ falls below approximately 60 mmHg, these sensors inhibit mitochondrial , activating and releasing calcium from ryanodine-sensitive stores, leading to . This redirects blood flow from poorly ventilated lung regions to better-oxygenated areas, optimizing ventilation-perfusion matching and systemic oxygenation without relying on extrinsic neural input. Central chemoreceptors, located in the , indirectly influence cardiac preload through their response to . Elevated CO₂ diffuses across the blood-brain barrier, lowering pH and stimulating these chemoreceptors to increase respiratory drive and . Enhanced diaphragmatic and intercostal muscle activity promotes venous return via the thoracic pump mechanism, augmenting right ventricular preload and overall . Mild further supports this by activating sympathoadrenal pathways that increase preload through vasodilation in systemic capacitance vessels. In , overactive peripheral chemoreceptors contribute to sympathetic overdrive in , exacerbating disease progression. Studies demonstrate hypersensitivity of chemoreceptors in chronic patients, correlating with heightened ventilatory responses to hypoxia and increased muscle sympathetic nerve activity, which promotes , , and adverse cardiac remodeling. Seminal work identified this hypersensitivity as a prognostic indicator of poor outcomes, while 2019 analyses confirmed its association with sympathetic neural overdrive mirroring left ventricular dysfunction severity across heart failure stages.

In Other Systems

In the endocrine system, chemoreceptors play a critical role in through specialized sensors in pancreatic beta cells. These cells utilize the GLUT2 to facilitate rapid , followed by that elevates the ATP/ADP ratio, leading to closure of ATP-sensitive (KATP) channels composed of Kir6.2 and SUR1 subunits. This closure depolarizes the , opening voltage-gated calcium channels and triggering insulin to lower blood glucose levels. Disruptions in this mechanism, such as mutations in KATP channel genes, underlie conditions like neonatal diabetes, highlighting the precision of beta-cell chemosensing. Chemoreceptors in the digestive system are primarily housed in enteroendocrine cells (EECs) of the intestinal mucosa, which detect luminal to orchestrate release and . These cells express taste-like G protein-coupled receptors, including the T1R3 subunit, which forms heterodimers such as T1R1/T1R3 to sense like L-glutamate, stimulating cholecystokinin (CCK) from I-cells in the and . CCK release promotes contraction and pancreatic enzyme while enhancing signals to the . Similarly, T1R2/T1R3 detects sugars, triggering GLP-1 release from L-cells to regulate glucose absorption and , demonstrating EECs as key chemosensors integrating nutrient cues with gastrointestinal function. In the , chemoreceptors encompass chemokine receptors that direct leukocyte migration via chemotactic gradients. The , activated by its ligand (SDF-1), mediates the homing of hematopoietic stem cells from to peripheral tissues and guides mature leukocytes, such as neutrophils and T cells, to sites. signaling involves Gαi proteins and β-arrestins, promoting cytoskeletal rearrangements for directed motility, adhesion to , and transendothelial migration essential for immune surveillance and response. For instance, orchestrates B-cell positioning in lymphoid germinal centers and thymocyte development, with deficiencies causing WHIM characterized by recurrent infections due to impaired trafficking. Emerging research highlights chemoreceptor involvement in the gut-brain axis, particularly through vagal afferent chemoreceptors that sense gut-derived signals influencing . Vagal nodose neurons, expressing receptors for hormones like CCK and GLP-1, detect postprandial nutrient states and relay information to the nucleus tractus solitarius, modulating hypothalamic centers to maintain balance. In , high-fat diets impair this signaling, reducing vagal sensitivity and contributing to , while alterations further disrupt EEC-vagal communication. Recent advances (2020s) reveal links to sensing, where gut-brain pathways influence hypothalamic signaling; for example, microbial metabolites enhance sensitivity via vagal routes, offering therapeutic targets like to combat resistance in obese individuals. These findings underscore the axis's role in metabolic disorders beyond traditional sensory functions.

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