Histamine H2 receptor

Mammalian protein found in Homo sapiens
HRH2
Identifiers
AliasesHRH2, H2R, histamine receptor H2, HH2R
External IDsOMIM: 142703 MGI: 108482 HomoloGene: 40613 GeneCards: HRH2
Gene location (Human)
Chromosome 5 (human)
Chr.Chromosome 5 (human)[1]
Chromosome 5 (human)
Genomic location for HRH2
Genomic location for HRH2
Band5q35.2Start175,658,030 bp[1]
End175,710,756 bp[1]
Gene location (Mouse)
Chromosome 13 (mouse)
Chr.Chromosome 13 (mouse)[2]
Chromosome 13 (mouse)
Genomic location for HRH2
Genomic location for HRH2
Band13 B1|13 28.4 cMStart54,346,148 bp[2]
End54,390,199 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • monocyte

  • blood

  • left ventricle

  • body of stomach

  • putamen

  • caudate nucleus

  • prefrontal cortex

  • bone marrow cells

  • nucleus accumbens

  • spleen
Top expressed in
  • internal carotid artery

  • epithelium of stomach

  • mucous cell of stomach

  • superior frontal gyrus

  • neuron

  • blood

  • secondary oocyte

  • supraoptic nucleus

  • entorhinal cortex

  • primary motor cortex
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
SpeciesHumanMouse
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 MbChr 13: 54.35 – 54.39 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

H2 receptors are positively coupled to adenylate cyclase via Gs 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.

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]


Central nervous system tissues[8]

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

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000113749 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000034987 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b c Hill SJ, Ganellin CR, Timmerman H, Schwartz JC, Shankley NP, Young JM, Schunack W, Levi R, Haas HL (Sep 1997). "International Union of Pharmacology. XIII. Classification of histamine receptors". Pharmacological Reviews. 49 (3): 253–78. PMID 9311023.
  6. ^ "Entrez Gene: HRH2 histamine receptor H2".
  7. ^ Cará, A. M.; Lopes-Martins, R. A.; Antunes, E.; Nahoum, C. R.; De Nucci, G. (1995). "The role of histamine in human penile erection". British Journal of Urology. 75 (2): 220–224. doi:10.1111/j.1464-410x.1995.tb07315.x. PMID 7850330.
  8. ^ a b c Maguire JJ, Davenport AP (29 November 2016). "H2 receptor". IUPHAR/BPS Guide to PHARMACOLOGY. International Union of Basic and Clinical Pharmacology. Retrieved 20 March 2017.
  9. ^ Bertaccini, Giulio; Coruzzi, Gabriella (1983). "Extragastric H2-Receptors". Journal of Clinical Gastroenterology. 5: 57–70. doi:10.1097/00004836-198312001-00006. PMID 6140284. S2CID 24764785.
  10. ^ Walter F., PhD. Boron (2005). Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. ISBN 1-4160-2328-3. Page 479

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, Yamada T (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, van Minnen J, Leurs R (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, Davio C (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, Hamada T, Sasaguri Y (Nov 2001). "Histamine increases the expression of LOX-1 via H2 receptor in human monocytic THP-1 cells". FEBS Letters. 508 (3): 345–9. doi:10.1016/S0014-5793(01)03073-3. PMID 11728449. S2CID 7257298.
  • Gutzmer R, Langer K, Lisewski M, Mommert S, Rieckborn D, Kapp A, Werfel T (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, Masters JN, Hancock AA (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.

  • v
  • t
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Neurotransmitter
Adrenergic
Purinergic
Serotonin
Other
Metabolites and
signaling molecules
Eicosanoid
Other
Peptide
Neuropeptide
Other
Miscellaneous
Taste, bitter
Orphan
Other
Adhesion
Orphan
Other
Taste, sweet
Other
Class F: Frizzled & Smoothened
Frizzled
Smoothened
  • v
  • t
  • e
H1
Agonists
Antagonists
  • Unknown/unsorted: Azanator
  • Belarizine
  • Elbanizine
  • Flotrenizine
  • GSK1004723
  • Napactadine
  • Tagorizine
  • Trelnarizine
  • Trenizine
H2
Agonists
Antagonists
H3
Agonists
Antagonists
H4
Agonists
Antagonists
See also
Receptor/signaling modulators
Monoamine metabolism modulators
Monoamine reuptake inhibitors