H₂ receptors are a type of histamine receptor found in many parts of the anatomy of humans and other animals. They are positively coupled to adenylate cyclase via G_s alpha subunit. It is a potent stimulant of cAMP production, which leads to activation of protein kinase A. PKA functions to phosphorylate certain proteins, affecting their activity. The drug betazole is an example of a histamine H₂ receptor agonist.

Histamine is a ubiquitous messenger molecule released from mast cells, enterochromaffin-like cells, and neurons. Its various actions are mediated by histamine receptors H₁, H₂, H₃ and H₄. The histamine receptor H₂ belongs to the rhodopsin-like family of G protein-coupled receptors. It is an integral membrane protein and stimulates gastric acid secretion. It also regulates gastrointestinal motility and intestinal secretion and is thought to be involved in regulating cell growth and differentiation. Histamine may play a role in penile erection.

Histamine H₂ receptors are expressed in the following tissues:

Activation of the H₂ receptor results in the following physiological responses:

This article incorporates text from the United States National Library of Medicine, which is in the public domain.