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International Union of Pharmacology XXXIII Mammalian gamma-aminobutyric acid(B) receptors: structure and function Bowery NG; Bettler B; Froestl W; Gallagher JP; Marshall F; Raiteri M; Bonner TI; Enna SJPharmacol Rev 2002[Jun]; 54 (2): 247-64The gamma-aminobutyric acid(B) (GABA(B)) 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 Ca(2+) 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 GABA(B) receptors, whereas the established GABA(A) receptor antagonists, bicuculline and picrotoxin, do not block GABA(B) receptors. The receptor is G(i)/G(o) 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 GABA(B) 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 GABA(B) receptor class. The advent of GABA(B1) knockout mice has also failed to provide support for multiple receptor types.|Animals[MESH]|GABA Agonists/chemistry/pharmacology[MESH]|GABA Antagonists/chemistry/pharmacology[MESH]|GABA-B Receptor Agonists[MESH]|GABA-B Receptor Antagonists[MESH]|Humans[MESH]|International Agencies[MESH]|Receptors, GABA-B/*physiology[MESH]|gamma-Aminobutyric Acid/*metabolism[MESH] |
