Histamine H1 receptor (IPR000921)
Short name: Histamine_H1_rcpt
Overlapping homologous superfamilies
- G protein-coupled receptor, rhodopsin-like (IPR000276)
- Histamine H1 receptor (IPR000921)
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 H1 receptor (also known as HH1R), which plays an important role in allergic responses. As a result, a number of selective receptor antagonists have been developed [PMID: 21618887, PMID: 7644667] for the treatment of symptoms associated to allergic and anaphylactic reactions, such as various inflammatory conditions, motion sickness, sleep and appetite suppression [PMID: 17490952]. Activation of the H1 receptor increases vascular permeability, stimulates sensory nerves of airways, and promotes chemotaxis of eosinophils, so can cause sneezing, nasal congestion and rhinorrhea. H1 antihistamines can act as inverse agonists, causing a shift in equilibrium of the H1 receptor to the inactivated state when bound to the H1 antihistamine [PMID: 11972592, PMID: 16402096, PMID: 17490952]. In the cerebral cortex, activation of H1 receptors leads to inhibition of cell membrane potassium channels, depolarizing the neurons and increases the resistance of the neuronal cell membrane, bringing the cell closer to its firing threshold and increasing the excitatory voltage produced by a given excitatory current. H1 receptor antagonists produce drowsiness because they oppose this action, reducing neuronal excitation [PMID: 8008209]. The H1 receptor is widely distributed in the periphery, notably smooth muscle, where it stimulates contraction (vasoconstriction). It is also found in the adrenal medulla, vascular endothelium and heart and throughout the CNS, including the cerebral cortex, spinal cord and cerebellum [PMID: 16402096, PMID: 11972592].
GO:0004969 histamine receptor activity
GO:0016021 integral component of membrane