Histamine H4 receptor (IPR008102)
Short name: Histamine_H4_rcpt
Overlapping homologous superfamilies
- G protein-coupled receptor, rhodopsin-like (IPR000276)
- Histamine H4 receptor (IPR008102)
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 H4 receptor (HH4R or H4) it is expressed primarily in cells and tissues of the immune system, including peripheral blood leukocytes, bone marrow, spleen, and the thymus, but is also present in the lung, colon, epicanthus, bone marrow, spleen and liver [PMID: 15274415], [PMID: 11179434]. As the H4 receptor is highly expressed in peripheral blood leukocytes and intestinal tissue, it makes the receptor a potential target in allergic and inflammatory diseases, particularly in the treatment of allergies and asthma [PMID: 19309354, PMID: 22202056]. Activation of the H4 receptor can also enhance the activity of other chemoattractants, like chemokines on eosinophils [PMID: 12626656] and upregulate adhesion of molecules [PMID: 17490952]. Thus, H4 receptor stimulation could enhance the inflammatory activity seen in allergic rhinitis.
GO:0004969 histamine receptor activity
GO:0016021 integral component of membrane
- PR01726 (HISTAMINEH4R)