Ixed Antagonistic Effects of Bilobalide at 1 Gabac Eceptor

bstract—Bilobalide was found to be a moderately potent ntagonist with a weak use-dependent effect at recombinant uman 1 GABAC receptors expressed in Xenopus oocytes sing two-electrode voltage clamp methodology. Antagoism of bilobalide at homomeric 1 GABAC receptors apeared to be mixed. At low concentration, bilobalide (3 M) aused a parallel right shift and surmountable GABA maxial response of the GABA dose-response curve characterstic of a competitive antagonist. At high concentrations, ilobalide (10–100 M) caused nonparallel right shifts and educed maximal GABA responses of GABA dose-response urves characteristic of a noncompetitive antagonist. The otency of bilobalide appears to be dependent on the conentrations of GABA and was more potent at lower GABA oncentrations. The mechanism of action of bilobalide at 1 ABAC receptors appears to be similar to that of the chloride hannel blocker picrotoxinin. © 2005 Published by Elsevier td on behalf of IBRO.