RT Journal Article SR Electronic T1 International Union of Pharmacology. XXXIII. Mammalian γ-Aminobutyric AcidB Receptors: Structure and Function JF Pharmacological Reviews JO Pharmacol Rev FD American Society for Pharmacology and Experimental Therapeutics SP 247 OP 264 DO 10.1124/pr.54.2.247 VO 54 IS 2 A1 N. G. Bowery A1 B. Bettler A1 W. Froestl A1 J. P. Gallagher A1 F. Marshall A1 M. Raiteri A1 T. I. Bonner A1 S. J. Enna YR 2002 UL http://pharmrev.aspetjournals.org/content/54/2/247.abstract AB The γ-aminobutyric acidB(GABAB) receptor was first demonstrated on presynaptic terminals where it serves as an autoreceptor and also as a heteroreceptor to influence transmitter release by suppressing neuronal Ca2+ conductance. Subsequent studies showed the presence of the receptor on postsynaptic neurones where activation produces an increase in membrane K+ conductance and associated neuronal hyperpolarization. (−)-Baclofen is a highly selective agonist for GABAB receptors, whereas the established GABAAreceptor antagonists, bicuculline and picrotoxin, do not block GABAB receptors. The receptor is Gi/Go protein-coupled with mixed effects on adenylate cyclase activity. The receptor comprises a heterodimer with similar subunits currently designated 1 and 2. These subunits are coupled via coiled-coil domains at their C termini. The evidence for splice variants is critically reviewed. Thus far, no unique pharmacological or functional properties have been assigned to either subunit or the variants. The emergence of high-affinity antagonists for GABAB receptors has enabled a synaptic role to be established. However, the antagonists have generally failed to establish the existence of pharmacologically distinct receptor types within the GABAB receptor class. The advent of GABAB1 knockout mice has also failed to provide support for multiple receptor types.