Abstract
Activation of the metabotropic γ-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 GABABantagonist, 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 GABABreceptor suggest novel mechanisms for producing pharmacologically distinct subtypes of G protein-coupled receptors.
Footnotes
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Send reprint requests to: Norman G. Bowery, Ph.D., University of Birmingham, Medical School, Department of Pharmacology, Edgbaston, Birmingham, B15 2TT UK. E-mail:n.g.bowery{at}bham.ac.uk
- Abbreviations:
- GABA
- γ-aminobutyric acid
- GBR
- γ-aminobutyric acidB receptor
- Received September 2, 1999.
- Accepted October 5, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
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