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JOURNAL ARTICLE
REVIEW
The Histamine H3 Receptor: Structure, Pharmacology, and Function.
Molecular Pharmacology 2016 November
Among the four G protein-coupled receptors (H1 -H4 ) identified as mediators of the biologic effects of histamine, the H3 receptor (H3 R) is distinguished for its almost exclusive expression in the nervous system and the large variety of isoforms generated by alternative splicing of the corresponding mRNA. Additionally, it exhibits dual functionality as autoreceptor and heteroreceptor, and this enables H3 Rs to modulate the histaminergic and other neurotransmitter systems. The cloning of the H3 R cDNA in 1999 by Lovenberg et al. allowed for detailed studies of its molecular aspects. In this work, we review the characteristics of the H3 R, namely, its structure, constitutive activity, isoforms, signal transduction pathways, regional differences in expression and localization, selective agonists, antagonists and inverse agonists, dimerization with other neurotransmitter receptors, and the main presynaptic and postsynaptic effects resulting from its activation. The H3 R has attracted interest as a potential drug target for the treatment of several important neurologic and psychiatric disorders, such as Alzheimer and Parkinson diseases, Gilles de la Tourette syndrome, and addiction.
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