霉菌毒素 Dihydroxyaflavinine 非竞争性抑制在爪蟾卵母细胞内表达的 GABA_A 受体通道  

FUNGAL TOXIN DIHYDROXYAFLAVININE INHIBITS NON-COMPETITIVELY GABA_A RECEPTOR CHANNEL EXPRESSED IN XENOPUS OOCYTES

作　　者：姚永[1] 李永新[1] 

机构地区：[1]中国科学院上海生理研究所,上海200031

出　　处：《生理学报》1991年第3期227-235,共9页Acta Physiologica Sinica

基　　金：国家博士后科学基金;90年度国家自然科学基金

摘　　要：Dihydroxyaflavinine 是黄曲霉菌(Aspergillus flavus)的吲哚类代谢物。我们将鸡脑mRNA 注入爪蟾卵母细胞表达得到 GABA_A 受体通道,然后用电压箝记录方法定量研究了dihydroxyaflavinine 对 GABA 电流反应的作用。Dihydroxyaflavinine 非竞争性阻断GABA 电流反应(K_I=12μmol/L),撤药后反应迅速恢复。作为比较,青霉素对 GABA_A受体的抑制作用随 GABA 浓度的升高而增加。浓度高达1μmol/L 苯二氮(艹卓)位点配体 Ro 15-1788(KD=0.6—2nmol/L)不能阻断10μmol/L dihydroxyaflavinine 的作用,说明 dihy-droxyaflavinine 不作用于 GABA_A 受体的苯二氮(艹卓)位点。Dihydroxyaflavinine 类似印防已毒素,表观上加速 GABA_A 受体的脱敏过程,而青霉素和荷包牡丹碱与此相反。Dihydroxyaflavinine is an indole-derived metabolite of Aspergillus flavus.Itsaction on GABA-induced response was quantitatively studied on the GABA_Areceptor expressed in Xenopus oocytes after injection of chick brain mRNA undervoltage-clamp conditions.Dihydroxyaflavinine inhibits GABA-induced currentnon-competitively with K_I=12μmol/L.This blockage is rapidly reversible.In comparison,the inhibitory effect of penicillin on GABA_A receptor is enhancedby increasing GABA concentration.Ro 15-1788(a benzodiazepine ligand withK_D=0.6—2 nmol/L)of concentration as high as 1 μmol/L,does not mask theaction of 10 μmol/L dihydroxyaflavinine,indicating that clihydroxyaflavinineacts on a site different from benzodiazepines.Dihydroxyaflavinine appears toexpedite desensitization of the receptor,which is similar to the action of picro-toxin and in contrast with that of penicillin and bicuculline.

关 键 词：霉菌毒素 GABAA受体 爪蟾卵母细胞 

分 类 号：R992[医药卫生—毒理学]