Gant D B, Cole R J, Valdes J J, Eldefrawi M E, Eldefrawi A T
Department of Pharmacology & Experimental Therapeutics, University of Maryland School of Medicine, Baltimore 21201.
Life Sci. 1987 Nov 9;41(19):2207-14. doi: 10.1016/0024-3205(87)90517-0.
The effects of four tremorgenic and one nontremorgenic mycotoxins were studied on gamma-aminobutyric acid (GABAA) receptor binding and function in rat brain and on binding of a voltage-operated Cl- channel in Torpedo electric organ. None of the mycotoxins had significant effect on [3H]muscimol or [3H]flunitrazepam binding to the GABAA receptor. However, only the four tremorgenic mycotoxins inhibited GABA-induced 36Cl- influx and [35S] t-butylbicyclophosphorothionate [( 35S]TBPS) binding in rat brain membranes, while the nontremorgenic verruculotoxin had no effect. Inhibition of [35S]TBPS binding by paspalinine was non-competitive. This suggests that tremorgenic mycotoxins inhibit GABAA receptor function by binding close to the receptor's Cl- channel. On the voltage-operated Cl- channel, only high concentrations of verruculogen and verruculotoxin caused significant inhibition of the channel's binding of [35S]TBPS. The data suggest that the tremorgenic action of these mycotoxins may be due in part to their inhibition of GABAA receptor function.
研究了四种震颤性霉菌毒素和一种非震颤性霉菌毒素对大鼠脑中γ-氨基丁酸（GABAA）受体结合及功能以及对电鳐电器官中电压门控氯离子通道结合的影响。这些霉菌毒素均对[3H]蝇蕈醇或[3H]氟硝西泮与GABAA受体的结合无显著影响。然而，只有四种震颤性霉菌毒素抑制了大鼠脑膜中GABA诱导的36Cl-内流和[35S]叔丁基双环磷硫代酸盐[（35S]TBPS）结合，而非震颤性的疣孢菌素则无此作用。雀稗麦角碱对[35S]TBPS结合的抑制作用是非竞争性的。这表明震颤性霉菌毒素通过靠近受体氯离子通道的结合来抑制GABAA受体功能。在电压门控氯离子通道上，只有高浓度的疣孢青霉毒素和疣孢菌素会显著抑制通道对[35S]TBPS的结合。数据表明，这些霉菌毒素的震颤作用可能部分归因于它们对GABAA受体功能的抑制。
