Journal
BIOCHEMICAL PHARMACOLOGY
Volume 73, Issue 8, Pages 1195-1204Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bcp.2007.01.008
Keywords
histamine H-3 receptor; pharmacology; splice variant; G protein-coupled receptor; signal transduction; dimerization
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The cloning of the histamine H-3 receptor (H3R) cDNA in 1999 by Lovenberg et al. [10] allowed detailed studies of its molecular aspects and indicated that the H3R can activate several signal transduction. pathways including G(i/o)-dependent inhibition of adenylyl cyclase, activation of phospholipase A(2), Akt and the mitogen activated kinase as well as the inhibition of the Na+/H+ exchanger and inhibition of K+-induced Ca2+ mobilization. Moreover, cloning of the H3R has led to the discovery several H3R isoforms generated through alternative splicing of the H3R mRNA. The H3R has gained the interest of many pharmaceutical companies as a potential drug target for the treatment of various important disorders like obesity, myocardial ischemia, migraine, inflammatory diseases and several CNS disorders like Alzheimer's disease, attention-deficit hyperactivity disorder and schizophrenia. In this paper, we review various molecular aspects of the hH(3)R including its signal transduction, dimerization and the occurrence of different H3R isoforms. (c) 2007 Elsevier Inc. All rights reserved.
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