Molecular aspects of the histamine H3 receptor

The cloning of the histamine H3 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 Gi/o-dependent inhibition of adenylyl cyclase, activation of phospholipase A2, 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 hH3R including its signal transduction, dimerization and the occurrence of different H3R isoforms.