摘要
目的:用大鼠海马脑片研究3,4-氨基吡啶(DAP)诱发去甲肾上腺素胞外钙-不依赖释放的机制。方法:大鼠海马脑片用[~3H]NE孵育后,进行表面灌流,测[~3H]NE释放。结果:在胞外无钙条件下,DAP能显著加强[~3H]NE释放,当用利血平使囊泡[~3H]NE排空,则DAP作用消失,用高浓度地昔帕明刺激IP_3-敏感的胞内Ca^(2+)储备库,能有力地增强[~3H]NE释放,而高浓度咖啡因对[~3H]NE释放只有很微弱的作用,丹曲林钠对DAP诱发[~3H]NE释放无任何抑制作用。结论:在胞外无钙条件下,DAP通过IP_3-敏感的Ca^(2+)储备库释放Ca^(2+),从而诱发囊泡内的去甲肾上腺素释放。
AIM: To study the mechanism for 3, 4-diamino-pyridine (DAP) evoking external Ca2+ -independent release of [3H] norepinephrine ([3H]NE). METHODS: Rat hippocampal slices were preincubated with [3H ] NE and superfused with medium. [3H ] NE release was determined. RESULTS: Under Ca2+-free conditions, DAP evoked [3H]NE release. In rats pretreated by reserpine, the effect of DAP was no longer detectable. Ca2+ chelator BAPTA-AM potently inhibited DAP-evoked [3H] NE release. Desi-pramine 100 - 500 μmol · L-1 strongly induced [3H ] NE release in a concentration-dependent manner, whereas caffeine 30 - 70 mmol · L-1 was slightly effective on [3H]NE release. The blocker of Ca2+ -induced Ca2+ releasable stores, dantrolene sodium did not attenuate DAP-evoked [3H]NE release. CONCLUSION: In the absence of extracellular Ca2+ , DAP evokes exocytotic release of [3H]NE from synaptic vesicles through liberation of internal Ca2+ from inositol 1, 4, 5-trisphosphate-sensitive Ca2+ stores.
出处
《中国药理学报》
CSCD
1996年第4期302-305,共4页
Acta Pharmacologica Sinica
基金
Project supported by the National Natural Science Foundation of China,№ 39370237
the Stiftung Volkswagenwerk,Germany.
关键词
去甲肾上腺素
海马
二氨基吡啶
利血平
钙
norepinephrine
hippocampus
3, 4- diaminopyridine
reserpine
BAPTA
dantrolene
desipramine