Molecular aspects of the histamine H3 receptor.
The cloning of the histamine H(3) receptor (H(3)R) cDNA in 1999 by Lovenberg et al. [10] allowed detailed studies of its molecular aspects and indicated that the H(3)R 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 Ca(2+) mobilization. Moreover, cloning of the H(3)R has led to the discovery several H(3)R isoforms generated through alternative splicing of the H(3)R mRNA. The H(3)R 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 H(3)R isoforms.
Bongers
Gerold
G
Leiden/Amsterdam Center for Drug Research, Department of Medicinal Chemistry, Vrije Universiteit Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands.
Bakker
Remko A
RA
Leurs
Rob
R
D000262:Adenylyl Cyclases / Q000378:metabolism; D017398:Alternative Splicing; D019281:Dimerization; D017442:Histamine Agonists / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology; D006801:Humans; D020033:Protein Isoforms / Q000378:metabolism; D018100:Receptors, Histamine H3 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D017442:Histamine Agonists; D006633:Histamine Antagonists; D020033:Protein Isoforms; D018100:Receptors, Histamine H3; D000262:Adenylyl Cyclases