Histamine H3 receptor

GWB-98ECA6

The H3 subclass of histamine receptors could mediate the histamine signals in CNS and peripheral nervous system. Signals through the inhibition of adenylate cyclase and displays high constitutive activity (spontaneous activity in the absence of agonist). Agonist stimulation of isoform 3 niether modified adenylate cyclase activity nor induced intracellular calcium mobilization.

Expressed predominantly in the CNS with the greatest expression in the thalamus and caudate nucleus. The various isoforms are mainly coexpressed in brain but their relative expression level varies in a region-specific manner. Isoform 3 and isoform 7 are highly expressed in the thalamus caudate nucleus and cerebellum while isoform 5 and isoform 6 show a poor expression. Isoform 5 and isoform 6 show a high expression in the amygdala substantia nigra cerebral cortex and hypothalamus. Isoform 7 is not found in hypothalamus or substantia nigra.

Belongs to the G-protein coupled receptor 1 family [view classification]. Summary: Histamine is a ubiquitous messenger molecule released from mast cells enterochromaffin-like cells and neurons. Its various actions are mediated by histamine receptors H1 H2 H3 and H4. Histamine receptor H3 belongs to the family 1 of G protein-coupled receptors. It is an integral membrane protein and can regulate neurotransmitter release. This receptor can also increase voltage-dependent calcium current in smooth muscles and innervates the blood vessels and the heart in cardiovascular system. [1] Leurs R. Bakker R. A. Timmerman H. and de Esch I. J. et al. The histamine H3 receptor: from gene cloning to H3 receptor drugs[2] Lippert U. Artuc M. Grutzkau A. Babina M. Guhl S. Haase I. Blaschke V. Zachmann K. Knosalla M. Middel P. et al. Human skin mast cells express H2 and H4 but not H3 receptors[3] Lozeva V. Tuomisto L. Tarhanen J. and Butterworth R. F. et al. Increased concentrations of histamine and its metabolite tele-methylhistamine and down-regulation of histamine H3 receptor sites in autopsied brain tissue from cirrhotic patients who died in hepatic coma[4] Wellendorph P. Goodman M. W. Burstein E. S. Nash N. R. Brann M. R. and Weiner D. M. Molecular cloning and pharmacology of functionally distinct isoforms of the human histamine H(3) receptor[5] Wiedemann P. Bonisch H. Oerters F. and Bruss M. et al. Structure of the human histamine H3 receptor gene (HRH3) and identification of naturally occurring variations[6] Lovenberg T. W. Roland B. L. Wilson S. J. Jiang X. Pyati J. Huvar A. Jackson M. R. Erlander M. G. Cloning and functional expression of the human histamine H3 receptor. [7] Nakamura T. Itadani H. Hidaka Y. Ohta M. Tanaka K. Molecular cloning and characterization of a new human histamine receptor HH4R. [8] Coge F. Guenin S. -P. Audinot V. Renouard-Try A. Beauverger P. Macia C. Ouvry C. Nagel N. Rique H. Boutin J. A. et al. Genomic organization and characterization of splice variants of the human histamine H3 receptor. [9] Wiedemann P. Boenisch H. Oerters F. Bruess M. Structure of the human histamine H3 receptor gene (HRH3) and identification of naturally occurring variations. [10] Ullmer C. Zirwes E. Lubbert H. Cloning and functional expression of the human histamine H3S receptor.