Interaction of anisatin with rat brain gamma-aminobutyric acidA receptors: allosteric modulation by competitive antagonists.
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 gamma-aminobutyric acid (GABA)A receptors, to rat brain membranes with an IC50 value of 0.43 microM. 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).
Department of Life Science and Biotechnology, Shimane University, Matsue, Japan.
E
E
Kakemoto
E
E
Okuyama
K
K
Nagata
Y
Y
Ozoe
D000345:Affinity Labels; D000494:Allosteric Regulation; D000731:Androstanes / Q000494:pharmacology; D000818:Animals; D001378:Azasteroids / Q000494:pharmacology; D001665:Binding Sites; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D018756:GABA Antagonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D007783:Lactones; D011724:Pyridazines / Q000494:pharmacology; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D012717:Sesquiterpenes; D013141:Spiro Compounds / Q000494:pharmacology*; D014316:Tritium
D000345:Affinity Labels; D000731:Androstanes; D001378:Azasteroids; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018756:GABA Antagonists; D007783:Lactones; D011724:Pyridazines; D011963:Receptors, GABA-A; D012717:Sesquiterpenes; D013141:Spiro Compounds; D014316:Tritium; C091518:1-(4-ethynylphenyl)-4-propyl-2,6,7-trioxabicyclo(2.2.2)octane; C049853:gabazine; C032061:RU 5135; C031244:anisatin