Kapus G, Bódi I, Pataki A, Gueritaud J, Székely J I, Tarnawa I
Institute for Drug Research, P.O. Box 82, H-1325, Budapest, Hungary.
Eur J Pharmacol. 2000 May 26;397(1):43-7. doi: 10.1016/s0014-2999(00)00302-2.
The effects of various (S)-alpha-amino-3-hydroxy-5-methyl-4-izoxazole-propionate (AMPA) receptor modulators on AMPA-induced whole-cell currents were compared in isolated rat cerebellar Purkinje cells. The positive modulators, aniracetam, cyclothiazide, 1-(1, 3-benzodioxol-5-ylcarbonyl)-piperidine (1-BCP), and 1-(quinoxaline-6-ylcarbonyl)-piperidine (BDP-12), dose-dependently potentiated the steady-state component of AMPA currents. The negative modulator, (-)1-(4-aminophenyl)-4-methyl-7, 8-methylenedioxy-4,5-dihydro-3-methylcarbamoyl-2,3-benzodiazepine (GYKI 53784), dose-dependently suppressed AMPA responses. Its concentration-response curve was shifted to the right in a parallel fashion by all positive modulators, indicating a competitive type of interaction. However, the relative potencies of the positive modulators were different with regard to the enhancement of AMPA responses and the reversal of GYKI 53784-induced inhibition, respectively. It is supposed that positive modulators act at multiple allosteric sites and that they interact with GYKI 53784 at only one of these sites.
在分离的大鼠小脑浦肯野细胞中比较了各种（S）-α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体调节剂对AMPA诱导的全细胞电流的影响。阳性调节剂阿尼西坦、环噻嗪、1-（1,3-苯并二氧杂环戊烯-5-基羰基）-哌啶（1-BCP）和1-（喹喔啉-6-基羰基）-哌啶（BDP-12）剂量依赖性地增强了AMPA电流的稳态成分。阴性调节剂（-）1-（4-氨基苯基）-4-甲基-7,8-亚甲二氧基-4,5-二氢-3-甲基氨基甲酰基-2,3-苯并二氮杂卓（GYKI 53784）剂量依赖性地抑制AMPA反应。所有阳性调节剂均使其浓度-反应曲线平行右移，表明存在竞争性相互作用类型。然而，阳性调节剂在增强AMPA反应和逆转GYKI 53784诱导的抑制方面的相对效力有所不同。推测阳性调节剂作用于多个变构位点，并且它们仅在其中一个位点与GYKI 53784相互作用。
