RT Journal Article
SR Electronic
T1 Differences in Agonist/Antagonist Binding Affinity and Receptor Transduction Using Recombinant Human γ-Aminobutyric Acid Type A Receptors
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 1150
OP 1156
DO 10.1124/mol.52.6.1150
VO 52
IS 6
A1 Ebert, Bjarke
A1 Thompson, Sally A.
A1 Saounatsou,  Koralia
A1 McKernan,  Ruth
A1 Krogsgaard-Larsen, Povl
A1 Wafford, Keith A.
YR 1997
UL http://molpharm.aspetjournals.org/content/52/6/1150.abstract
AB Using human γ-aminobutyric acid type A (GABAA) receptor subunit combinations, expressed in cell lines and Xenopus laevis oocytes, the pharmacology of a number of ligands interacting directly with the GABA recognition site has been studied in [3H]muscimol binding and electrophysiologically. The binding affinity of GABAA agonist and antagonist ligands showed small but statistically significant dependence on the subunit composition of receptors that include γ2 and different α and β subunits. The potency of antagonist ligands was largely independent of receptor subunit composition, whereas the composition of receptors expressed in oocytes strongly influenced the EC50 value of agonists. An apparent reciprocal correlation between subunits favoring agonist binding and antagonist binding, respectively, was observed. Whereas antagonists showed comparable potencies in binding and functional studies, the potency of agonists in binding studies was generally two to three orders of magnitude higher than the agonist potencies measured electrophysiologically. 5-(4-Piperidyl)isothiazol-3-ol, which behaves as a low efficacy partial agonist at GABAA receptors in cultured cortical neurons, showed no efficacy in oocytes, but produced pure antagonist effects with a binding/functional affinity ratio between those observed for the agonists and antagonists. It is concluded that the GABAAreceptor mechanisms transducing binding into physiological response, but not the binding per se, is dependent on the receptor subunit composition.