Interaction of anisatin with rat brain γ-aminobutyric acid a receptors: allosteric modulation by competitive antagonists

Abstract

Anisatin, a toxic sesquiterpene isolated from the Japanese star anise ( Illicium anisatum L.), competitively inhibited the specific binding of [ 3H]4′-ethynyl-4- n-propylbicycloorthobenzoate ([ 3H]EBOB), a non-competitive antagonist of γ-aminobutyric acid (GABA) A receptors, to rat brain membranes with an ic 50 value of 0.43 μM. R 5135, a competitive GABA antagonist, decreased the potency of anisatin in inhibiting [ 3H]EBOB binding in a negatively cooperative manner. Two other competitive antagonists, SR 95531 (gabazine) and (−)-bicuculline methiodide, had similar effects. On the other hand, R 5135 exerted little influence on the potencies of the other non-competitive antagonists tested: EBOB, picrotoxinin, isopropylbicyclophosphate, and dieldrin. Thus, anisatin was clearly different from the other non-competitive antagonists in responding to the action of competitive antagonists on GABA A receptors. These findings suggest that the binding region of anisatin might overlap with that of the other non-competitive antagonists, but that anisatin must interact with other specific region(s).