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Vol. 292, Issue 1, 2-7, January 2000

gamma -Aminobutyric AcidB Receptors: First of the Functional Metabotropic Heterodimers

Norman G. Bowery and S. J. Enna

Department of Pharmacology, The Medical School, University of Birmingham, Edgbaston, Birmingham, United Kingdom (N.G.B.); and Department of Pharmacology, Toxicology and Therapeutics, University of Kansas, School of Medicine, Kansas City, Kansas (S.J.E.)

Activation of the metabotropic gamma -aminobutyric acidB (GABAB) receptor increases K+ conductance and decreases Ca2+ channel activity in neuronal membranes. Studies with a number of new GABAB receptor agonists and antagonists reveal that in addition to their muscle relaxant effects, agonists display analgesic activity and reduce the craving for cocaine. With regard to GABAB receptor antagonists, preclinical data suggest they improve cognitive performance and possess antidepressant and antiepileptic potential. With a high-affinity GABAB antagonist, the structural properties of the receptor were characterized through expression cloning. Moreover, it has been found that expression of a fully functional GABAB receptor requires coupling between two separate and distinct gene products: GABAB R1 and GABAB R2. Besides being the first example of a functional heterodiameric metabotropic receptor, the components and molecular configuration of the GABAB receptor suggest novel mechanisms for producing pharmacologically distinct subtypes of G protein-coupled receptors.

0022-3565/0/2921-0002$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 2000 by The American Society for Pharmacology and Experimental Therapeutics


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