GABAB receptors: physiological functions and mechanisms of diversity

Advances in Pharmacology
Audrée PinardBernhard Bettler

Abstract

GABA(B) receptors are the G-protein-coupled receptors (GPCRs) for gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the central nervous system. GABA(B) receptors are implicated in the etiology of a variety of psychiatric disorders and are considered attractive drug targets. With the cloning of GABA(B) receptor subunits 13 years ago, substantial progress was made in the understanding of the molecular structure, physiology, and pharmacology of these receptors. However, it remained puzzling that native studies demonstrated a heterogeneity of GABA(B) responses that contrasted with a very limited diversity of cloned GABA(B) receptor subunits. Until recently, the only firmly established molecular diversity consisted of two GABA(B1) subunit isoforms, GABA(B1a) and GABA(B1b), which assemble with GABA(B2) subunits to generate heterodimeric GABA(B(1a,2)) and GABA(B(1b,2)) receptors. Using genetic, ultrastructural, biochemical, and electrophysiological approaches, it has been possible to identify functional properties that segregate with these two receptors. Moreover, receptor modifications and factors that can alter the receptor response have been identified. Most importantly, recent data reveal the existence of a f...Continue Reading

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