Molecular aspects of the histamine H3 receptor

Abstract 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.