The Histamine H3 Receptor: Structure, Pharmacology, and Function.
Gustavo Nieto-Alamilla1, Ricardo Márquez-Gómez1, Ana-Maricela García-Gálvez1
1Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados (Cinvestav-IPN), Zacatenco, Ciudad de México, México.
Molecular Pharmacology
|August 27, 2016
Summary
The H3 receptor (H3R), primarily in the nervous system, modulates neurotransmitter systems. Its unique characteristics make it a promising drug target for neurological and psychiatric conditions like Alzheimer's and Parkinson's diseases.
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- Histamine acts via four G protein-coupled receptors (H1-H4).
- The H3 receptor (H3R) is predominantly expressed in the nervous system.
- H3R exhibits dual autoreceptor and heteroreceptor functions, modulating neurotransmitter systems.
Purpose of the Study:
- To review the molecular characteristics of the H3 receptor.
- To explore H3R's potential as a therapeutic target for neurological and psychiatric disorders.
Main Methods:
- Review of molecular studies following H3R cDNA cloning in 1999.
- Analysis of H3R structure, isoforms, signaling, expression, and pharmacology.
- Examination of H3R's role in presynaptic and postsynaptic neurotransmission.
Main Results:
- Detailed characterization of H3R structure, constitutive activity, and diverse isoforms.
- Understanding of H3R's signal transduction pathways and regional expression.
- Identification of selective agonists, antagonists, inverse agonists, and dimerization partners.
- Elucidation of H3R's presynaptic and postsynaptic effects on neurotransmitter release.
Conclusions:
- The H3 receptor's unique properties and broad modulatory functions are well-established.
- H3R represents a significant therapeutic target for conditions including Alzheimer's disease, Parkinson's disease, Tourette syndrome, and addiction.
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