TY - JOUR T1 - International Union of Pharmacology. XXXIII. Mammalian γ-Aminobutyric Acid<sub>B</sub> Receptors: Structure and Function JF - Pharmacological Reviews JO - Pharmacol Rev SP - 247 LP - 264 DO - 10.1124/pr.54.2.247 VL - 54 IS - 2 AU - N. G. Bowery AU - B. Bettler AU - W. Froestl AU - J. P. Gallagher AU - F. Marshall AU - M. Raiteri AU - T. I. Bonner AU - S. J. Enna Y1 - 2002/06/01 UR - http://pharmrev.aspetjournals.org/content/54/2/247.abstract N2 - 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. ER -