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. 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) Band 5q35.2 Start 175,658,030 bp End 175,710,756 bp
Gene location (Mouse) Chr. Chromosome 13 (mouse) Band 13 B1|13 28.4 cM Start 54,346,148 bp End 54,390,199 bp
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
Wikidata
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Function

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.

Tissue distribution

Histamine H₂ receptors are expressed in the following tissues:

Peripheral tissues

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

Central nervous system tissues

• 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.
• Inhibition of neutrophil activation and chemotaxis

See also

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

Further reading

• Del Valle J, Gantz I (Nov 1997). "Novel insights into histamine H2 receptor biology". The American Journal of Physiology. 273 (5 Pt 1): G987-96. doi:10.1152/ajpgi.1997.273.5.G987. PMID 9374694.
• Gantz I, Munzert G, Tashiro T, Schäffer M, Wang L, DelValle J, et al. (Aug 1991). "Molecular cloning of the human histamine H2 receptor" (PDF). Biochemical and Biophysical Research Communications. 178 (3): 1386–92. doi:10.1016/0006-291X(91)91047-G. hdl:2027.42/29176. PMID 1714721.
• Vannier E, Dinarello CA (Apr 1994). "Histamine enhances interleukin (IL)-1-induced IL-6 gene expression and protein synthesis via H2 receptors in peripheral blood mononuclear cells". The Journal of Biological Chemistry. 269 (13): 9952–6. doi:10.1016/S0021-9258(17)36975-2. PMID 7511596.
• Smit MJ, Timmerman H, Alewijnse AE, Punin M, van den Nieuwenhof I, Blauw J, et al. (Sep 1995). "Visualization of agonist-induced internalization of histamine H2 receptors". Biochemical and Biophysical Research Communications. 214 (3): 1138–45. doi:10.1006/bbrc.1995.2404. PMID 7575521.
• Nishi T, Koike T, Oka T, Maeda M, Futai M (May 1995). "Identification of the promoter region of the human histamine H2-receptor gene". Biochemical and Biophysical Research Communications. 210 (2): 616–23. doi:10.1006/bbrc.1995.1703. PMID 7755641.
• Traiffort E, Vizuete ML, Tardivel-Lacombe J, Souil E, Schwartz JC, Ruat M (Jun 1995). "The guinea pig histamine H2 receptor: gene cloning, tissue expression and chromosomal localization of its human counterpart". Biochemical and Biophysical Research Communications. 211 (2): 570–7. doi:10.1006/bbrc.1995.1851. PMID 7794271.
• Orange PR, Heath PR, Wright SR, Pearson RC (May 1996). "Allelic variations of the human histamine H2 receptor gene". NeuroReport. 7 (7): 1293–6. doi:10.1097/00001756-199605170-00015. PMID 8817552.
• Elenkov IJ, Webster E, Papanicolaou DA, Fleisher TA, Chrousos GP, Wilder RL (Sep 1998). "Histamine potently suppresses human IL-12 and stimulates IL-10 production via H2 receptors". Journal of Immunology. 161 (5): 2586–93. doi:10.4049/jimmunol.161.5.2586. PMID 9725260. S2CID 6034918.
• Murakami H, Sun-Wada GH, Matsumoto M, Nishi T, Wada Y, Futai M (May 1999). "Human histamine H2 receptor gene: multiple transcription initiation and tissue-specific expression". FEBS Letters. 451 (3): 327–31. doi:10.1016/S0014-5793(99)00618-3. PMID 10371214. S2CID 33650873.
• Wang LD, Wang M, Todisco A, Grand E, del Valle J (Jun 2000). "The human histamine H(2) receptor regulates c-jun and c-fos in a differential manner". American Journal of Physiology. Cell Physiology. 278 (6): C1246-55. doi:10.1152/ajpcell.2000.278.6.c1246. PMID 10837353.
• Suh BC, Lee H, Jun DJ, Chun JS, Lee JH, Kim KT (Aug 2001). "Inhibition of H2 histamine receptor-mediated cation channel opening by protein kinase C in human promyelocytic cells". Journal of Immunology. 167 (3): 1663–71. doi:10.4049/jimmunol.167.3.1663. PMID 11466390.
• Brew OB, Sullivan MH (Sep 2001). "Localisation of mRNAs for diamine oxidase and histamine receptors H1 and H2, at the feto-maternal interface of human pregnancy". Inflammation Research. 50 (9): 449–52. doi:10.1007/PL00000269. PMID 11603849. S2CID 28710647.
• Shayo C, Fernandez N, Legnazzi BL, Monczor F, Mladovan A, Baldi A, et al. (Nov 2001). "Histamine H2 receptor desensitization: involvement of a select array of G protein-coupled receptor kinases". Molecular Pharmacology. 60 (5): 1049–56. doi:10.1124/mol.60.5.1049. hdl:11336/31340. PMID 11641433. S2CID 24358588.
• Tanimoto A, Murata Y, Nomaguchi M, Kimura S, Arima N, Xu H, et al. (Nov 2001). "Histamine increases the expression of LOX-1 via H2 receptor in human monocytic THP-1 cells". FEBS Letters. 508 (3): 345–9. Bibcode:2001FEBSL.508..345T. doi:10.1016/S0014-5793(01)03073-3. PMID 11728449. S2CID 7257298.
• Gutzmer R, Langer K, Lisewski M, Mommert S, Rieckborn D, Kapp A, et al. (Mar 2002). "Expression and function of histamine receptors 1 and 2 on human monocyte-derived dendritic cells". The Journal of Allergy and Clinical Immunology. 109 (3): 524–31. doi:10.1067/mai.2002.121944. PMID 11898002.
• Esbenshade TA, Kang CH, Krueger KM, Miller TR, Witte DG, Roch JM, et al. (Feb 2003). "Differential activation of dual signaling responses by human H1 and H2 histamine receptors". Journal of Receptor and Signal Transduction Research. 23 (1): 17–31. doi:10.1081/RRS-120018758. PMID 12680587. S2CID 24392073.

External links

• "Histamine Receptors: H₂". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
• H2+receptors at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

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