Ruzicka B B, Jhamandas K
Department of Pharmacology and Toxicology, Faculty of Medicine, Queen's University, Kingston, Ontario, Canada.
J Pharmacol Exp Ther. 1991 Jun;257(3):1025-33.
The present study evaluated the effects of high K+ and four excitatory amino acids (EAAs) on the release of met-enkephalin-like immunoreactivity (ME-i.r.) from slices of the rat striatum and globus pallidus. High K+ (15-50 mM) increased the release of ME-i.r. in a concentration-dependent manner in both regions, the release response in the globus pallidus being consistently greater than in the striatum. This release was highly Ca(++)-dependent and was significantly enhanced in the absence of external Mg++. D-2-Amino-7-phosphonoheptanoic acid (0.5 mM), a competitive N-methyl-D-aspartate (NMDA) receptor antagonist, did not alter this enhanced action of K+, suggesting that the activation of NMDA receptors by an endogenous agonist did not contribute to the enhancement. Exposure of pallidal or striatal slices to four EAA receptor agonists, NMDA, L-glutamate, kainate (KA) and quisqualate, increased the release of ME-i.r. above the base line, an effect that was Ca(++)-dependent. Both L-glutamate and NMDA, at concentrations of 1 and 5 mM, produced a graded increase in the ME-i.r. release, but a higher concentration (10 mM) produced a lower release. In both regions the NMDA (5 mM)-evoked release was effectively inhibited by Mg++ (1.2 mM), 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) (5 microM), a competitive NMDA receptor antagonist and thienylcyclohexylpiperidine (10 microM), a noncompetitive NMDA receptor antagonist. Tetrodotoxin (0.3 microM), a Na+ channel blocker, did not affect the NMDA-evoked release of ME-i.r. in the striatum, but decreased it by 52% in the globus pallidus.(ABSTRACT TRUNCATED AT 250 WORDS)
本研究评估了高钾离子和四种兴奋性氨基酸(EAAs)对大鼠纹状体和苍白球切片中脑啡肽样免疫反应性(ME-i.r.)释放的影响。高钾离子(15 - 50 mM)在两个区域均以浓度依赖性方式增加ME-i.r. 的释放,苍白球中的释放反应始终大于纹状体。这种释放高度依赖钙离子,并且在无细胞外镁离子的情况下显著增强。竞争性N-甲基-D-天冬氨酸(NMDA)受体拮抗剂D-2-氨基-7-磷酸庚酸(0.5 mM)并未改变钾离子的这种增强作用,表明内源性激动剂对NMDA受体的激活并未促成这种增强。将苍白球或纹状体切片暴露于四种EAA受体激动剂,即NMDA、L-谷氨酸、海人藻酸(KA)和quisqualate,可使ME-i.r. 的释放高于基线水平,这一效应依赖钙离子。L-谷氨酸和NMDA在1和5 mM浓度时,使ME-i.r. 的释放呈分级增加,但更高浓度(10 mM)时释放降低。在两个区域中,NMDA(5 mM)诱发的释放均被镁离子(1.2 mM)、竞争性NMDA受体拮抗剂3-(2-羧基哌嗪-4-基)-丙基-1-膦酸(CPP)(5 microM)和非竞争性NMDA受体拮抗剂噻吩环己基哌啶(10 microM)有效抑制。钠离子通道阻滞剂河豚毒素(0.3 microM)不影响NMDA诱发的纹状体中ME-i.r. 的释放,但使苍白球中的释放降低了52%。(摘要截断于250字)