histamine receptor subtypes H3R and H4R, member of the class A family of seven-transmembrane G protein-coupled receptors
This group includes histamine subtypes H3R and H4R, members of the histamine receptor family, which belong to the class A of GPCRs. Histamine plays a key role as chemical mediator and neurotransmitter in various physiological and pathophysiological processes in the central and peripheral nervous system. Histamine exerts its functions by binding to four different G protein-coupled receptors (H1-H4). The H3 and H4 receptors couple to the G(i)-proteins, which leading to the inhibition of cAMP formation. The H3R receptor functions as a presynaptic autoreceptors controlling histamine release and synthesis. The H4R plays an important role in histamine-mediated chemotaxis in mast cells and eosinophils. All GPCRs have a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes.