Mixed antagonistic effects of bilobalide at ρ1 GABAC receptor

Bilobalide was found to be a moderately potent antagonist with a weak use-dependent effect at recombinant human ρ1 GABAC receptors expressed in Xenopus oocytes using two-electrode voltage clamp methodology. Antagonism of bilobalide at homomeric ρ1 GABAC receptors appeared to be mixed. At low concentration, bilobalide (3μM) caused a parallel right shift and surmountable GABA maximal response of the GABA dose-response curve characteristic of a competitive antagonist. At high concentrations, bilobalide (10–100μM) caused nonparallel right shifts and reduced maximal GABA responses of GABA dose-response curves characteristic of a noncompetitive antagonist. The potency of bilobalide appears to be dependent on the concentrations of GABA and was more potent at lower GABA concentrations. The mechanism of action of bilobalide at ρ1 GABAC receptors appears to be similar to that of the chloride channel blocker picrotoxinin.