Purification and Molecular Characterization of the -γ-aminobutyric acidA Receptor

Abstract

Abstract γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian central nervous system. GABA mediates its effects via the specific interaction with GABA receptors of which two major subclasses have been defined on both a pharmacological and a functional basis. GABAA receptors are ligandgated chlorideion channels and are sensitive to the competitive GABAA receptor antagonist, bicuculline, whereas GABAB receptors are bicuculline-insensitive but baclofen, a GABAB receptor agonist, sensitive. GABAB-receptor activation results in the interaction with a guanine nucleotide binding protein and subsequent modulation of adenylate cyclase activity, of Ca2+ and/or K+ channel activity. GABAA receptors have a complex pharmacology, which has greatly facilitated the understanding of their structure, whereas to date there is little information available on GABAB receptors other than, by analogy with other receptors that act via second messenger systems, that they are proteins consisting of a single polypeptide chain.