Molecular Biology, Pharmacology, and Physiology of GABAC Receptors

The first edition of The GABA Receptors (Enna, 1983) made no reference to the subtype of GABA receptors now known as GABA C receptors, i.e., receptors for the inhibitory neurotransmitter GABA that are insensitive to the GABA A antagonist, bicuculline, and to the GABA B agonist, baclofen. Bowery (1993), in his chapter on the classification of GABA receptors, reported that the possible existence of bicuculline-insensitive GABA receptors had been considered, e.g., Andrews and Johnston (1979) postulated that “GABA might act at a population of bicuculline-insensitive sites in a folded conformation whereas it acts at bicuculline-sensitive receptors in an extended conformation.” Bowery continued, “The idea arose from studies with compounds such as cis -4-aminocrotonic acid that depress neuronal firing but are unaffected by bicuculline. Although this postulate is interesting, a simultaneous activation of these sites by GABA in the presence of bicuculline was never shown. To designate a receptor ‘GABA site,’ it surely must be activated by GABA. Perhaps under the right conditions GABA may be an agonist at the site.” These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.