Histamine H2 receptor (IPR000503)
Short name: Histamine_H2_rcpt
Overlapping homologous superfamilies
- G protein-coupled receptor, rhodopsin-like (IPR000276)
- Histamine H2 receptor (IPR000503)
Histamine plays an important role in a variety of pathophysiological conditions. In allergic conditions, histamine is released from basophils and mast cells and is responsible for symptoms of allergic conditions of the skin and airways. In the gastric mucosa, gastric induced histamine release stimulates parietal cells to secrete gastric acid. In the central nervous system (CNS), histamine is synthesized in specific neurons that are localized in the posterior hypothalamus. These neurons are involved in a variety of important physiological functions, including the regulation of the sleep-wake cycle, cardiovascular control, regulation of the hypothalamic pituitary adrenal-axis, learning and memory [PMID: 16402096, PMID: 19772756, PMID: 12113221, PMID: 17490952, PMID: 19843401].
Histamine exerts its biological effects by binding to and activating four distinct separate rhodopsin-like G protein-coupled receptors-histamine H1 receptor, histamine H2 receptor, histamine H3 receptor, and histamine H4 receptor. Each of the histamine receptors produce a functional response, but their mechanism differs. The H1 receptor couples to Gq/11 stimulating phospholipase C, whereas the H2 receptor interacts with Gs to activate adenylyl cyclase [PMID: 9311023]. The H3 and H4 receptors couple to Gi proteins to inhibit adenylyl cyclase, and to stimulate MAPK in the case of the H3 receptor [PMID: 12626656, PMID: 11179434].
This entry represents the histamine H2 receptor (also known as HH2R). It is located in parietal cells found in the stomach and in the heart and has a limited distribution in vascular smooth muscle and cells of the immune system. H2 receptors primarily stimulate gastric acid secretion and vasodilation, H2 antagonists are therefore used in the clinical treatment of peptic ulceration and asthma [PMID: 9374694, PMID: 21618887, PMID: 7644667]. Activation of the H2 receptor results in physiological responses, including stimulation of suppressor T cells, decrease in neutrophil and basophil chemotaxis and activation, proliferation of lymphocytes and activity of natural killer cells [PMID: 17490952]. H2 receptors are a potent stimulant of cAMP production [PMID: 9311023] and increases intracellular Ca2+ concentrations and releases Ca2+ from the intracellular stores [PMID: 10511481]. A combination of both H1 and H2 antihistamines block all the systemic activities of histamine [PMID: 7299000, PMID: 2861221, PMID: 7067399] so the activation of the H2 receptor is likely to contribute to the increased vascular permeability prompted by H1 receptor stimulation. Thus, a combination of H1 and H2 receptor activation contributes to nasal airway swelling and rhinorrhea [PMID: 2567579].
- PR00531 (HISTAMINEH2R)