Histamine H4 receptor (IPR008102)

Short name: Histamine_H4_rcpt

Overlapping homologous superfamilies


Family relationships


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 terms

Biological Process

GO:0007186 G-protein coupled receptor signaling pathway
GO:0006954 inflammatory response
GO:0007204 positive regulation of cytosolic calcium ion concentration
GO:0043408 regulation of MAPK cascade

Molecular Function

GO:0004969 histamine receptor activity

Cellular Component

GO:0016021 integral component of membrane

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.