Eells J T, Dubocovich M L
Department of Pharmacology, Northwestern University Medical School, Chicago, Illinois.
J Pharmacol Exp Ther. 1988 Aug;246(2):514-21.
The effects of the synthetic pyrethroid insecticide fenvalerate ([R,S]-alpha-cyano-3-phenoxybenzyl[R,S]-2-(4-chlorophenyl)-3- methylbutyrate) on neurotransmitter release in rabbit brain slices were investigated. Fenvalerate evoked a calcium-dependent release of [3H]dopamine and [3H]acetylcholine from rabbit striatal slices that was concentration-dependent and specific for the toxic stereoisomer of the insecticide. The release of [3H]dopamine and [3H]acetylcholine by fenvalerate was modulated by D2 dopamine receptor activation and antagonized completely by the sodium channel blocker, tetrodotoxin. These findings are consistent with an action of fenvalerate on the voltage-dependent sodium channels of the presynaptic membrane resulting in membrane depolarization, and the release of dopamine and acetylcholine by a calcium-dependent exocytotic process. In contrast to results obtained in striatal slices, fenvalerate did not elicit the release of [3H]norepinephrine or [3H]acetylcholine from rabbit hippocampal slices indicative of regional differences in sensitivity to type II pyrethroid actions.
研究了合成拟除虫菊酯杀虫剂氰戊菊酯([R,S]-α-氰基-3-苯氧基苄基[R,S]-2-(4-氯苯基)-3-甲基丁酸酯)对兔脑片神经递质释放的影响。氰戊菊酯引起兔纹状体切片中[3H]多巴胺和[3H]乙酰胆碱的钙依赖性释放,这种释放具有浓度依赖性,且对该杀虫剂的毒性立体异构体具有特异性。氰戊菊酯引起的[3H]多巴胺和[3H]乙酰胆碱释放受D2多巴胺受体激活调节,并被钠通道阻滞剂河豚毒素完全拮抗。这些发现与氰戊菊酯作用于突触前膜的电压依赖性钠通道导致膜去极化,以及通过钙依赖性胞吐过程释放多巴胺和乙酰胆碱的作用一致。与在纹状体切片中获得的结果相反,氰戊菊酯未引起兔海马切片中[3H]去甲肾上腺素或[3H]乙酰胆碱的释放,这表明对II型拟除虫菊酯作用的敏感性存在区域差异。