Histamine H2 receptor

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.^[5] PKA functions to phosphorylate certain proteins, affecting their activity. The drug betazole is an example of a histamine H₂ receptor agonist.

HRH2
Identifiers
Aliases	HRH2, H2R, histamine receptor H2, HH2R
External IDs	OMIM: 142703; MGI: 108482; HomoloGene: 40613; GeneCards: HRH2; OMA:HRH2 - orthologs
Gene location (Human) Chr. Chromosome 5 (human)[1] Band 5q35.2 Start 175,658,030 bp[1] End 175,710,756 bp[1]
Gene location (Mouse) Chr. Chromosome 13 (mouse)[2] Band 13 B1|13 28.4 cM Start 54,346,148 bp[2] End 54,390,199 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in monocyte blood granulocyte left ventricle apex of heart body of stomach putamen caudate nucleus myocardium of left ventricle prefrontal cortex Top expressed in granulocyte internal carotid artery epithelium of stomach mucous cell of stomach primary visual cortex superior frontal gyrus neuron blood decidua dentate gyrus of hippocampal formation granule cell More reference expression data BioGPS More reference expression data
Gene ontology Molecular function G protein-coupled receptor activity signal transducer activity histamine receptor activity G protein-coupled serotonin receptor activity neurotransmitter receptor activity Cellular component integral component of membrane membrane plasma membrane integral component of plasma membrane dendrite Biological process visual learning epithelial cell morphogenesis gastric acid secretion G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger memory toxin transport regulation of synaptic plasticity gastrin-induced gastric acid secretion positive regulation of vasoconstriction immune response digestive tract development signal transduction gland development histamine-induced gastric acid secretion G protein-coupled receptor signaling pathway chemical synaptic transmission G protein-coupled serotonin receptor signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3274 15466 Ensembl ENSG00000113749 ENSMUSG00000034987 UniProt P25021 P97292 RefSeq (mRNA) NM_001131055 NM_022304 NM_001367711 NM_001393460 NM_001393461 NM_001010973 NM_008286 RefSeq (protein) NP_001124527 NP_001354640 NP_001010973 Location (UCSC) Chr 5: 175.66 – 175.71 Mb Chr 13: 54.35 – 54.39 Mb PubMed search [3] [4]
Wikidata
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Function

Histamine is a ubiquitous messenger molecule released from mast cells, enterochromaffin-like cells, and neurons.^[5] 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.^[6] Histamine may play a role in penile erection.^[7]

Tissue distribution

Histamine H₂ receptors are expressed in the following tissues:

Peripheral tissues^[5][8]

• Gastric parietal cells (oxyntic cells)
• Vascular smooth muscle
• Neutrophils
• Mast cells
• Heart
• Genitourinary system^[9] (uterus, bladder)

Central nervous system tissues^[8]

• Caudate–putamen
• Cerebral cortex (external layers)
• Hippocampal formation
• Dentate nucleus of the cerebellum

Physiological responses

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

• Stimulation of gastric acid secretion (Target of anti-histaminergics (H₂ receptors) for peptic ulcer disease and GERD)
• Smooth muscle relaxation (Experimental histamine H₂ receptor agonist used for asthma and COPD)
• Inhibit antibody synthesis, T-cell proliferation and cytokine production
• Vasodilation – PKA activity causes phosphorylation of MLCK, decreasing its activity, resulting in MLC of myosin being dephosphorylated by MLCP and thus inhibiting contraction. The smooth muscle relaxation leads to vasodilation.^[10]
• Inhibition of neutrophil activation and chemotaxis^[8]

See also

• H₂-receptor antagonist
• Histamine H₁-receptor
• Histamine H₃-receptor
• Histamine H₄-receptor