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目的:研究DA和Glu及其受体激动剂/拮抗剂对大鼠纹状体脑片Ca~(2+)/CaM依赖性蛋白激酶Ⅱ(CCDPKⅡ)、cAMP依赖性蛋白激酶(PKA)活性及乳酸脱氢酶(LDH)释放的影响,以探讨纹状体DA和Glu两个神经递质系统的相互作用。方法:用~(32)P掺入法测定大鼠纹状体脑片CCDPKⅡ和PKA活性,用比色法测定LDH的释放。结果:(1)NMDA受体拮抗剂MK-801能拮抗DA、D_1激动剂SKF 38393和D_2激动剂LY 171555对CCDPKⅡ活性的抑制作用。D_1拮抗剂SCH 23390和D_2拮抗剂spiperone均能拮抗Glu诱导的CCDPKⅡ活性降低。(2)DA和SKF 38393显著增加纹状体脑片PKA活性,MK-801可降低这种作用。(3)DA和Glu增加LDH的释放并与浓度成正比。MK-801拮抗DA诱导的LDH释放增加;spiperone能显著减少Glu诱导的纹状体神经元LDH释放。结论:DA和Glu的相互作用对调节纹状体神经元CCDPKⅡ和PKA活性及细胞功能是非常重要的。
AIM: To investigate the effects of DA and Glu and its receptor agonists / antagonists on the activity of Ca 2+ / CaM-dependent protein kinase Ⅱ (CCDPKⅡ), cAMP-dependent protein kinase (PKA) in rat striatum and Lactate dehydrogenase (LDH) release to explore the interaction of the two neurotransmitter systems of the striatum DA and Glu. Methods: CCDPK Ⅱ and PKA activity in rat striatum slices were determined by ~ (32) P incorporation method. LDH release was measured by colorimetry. Results: (1) NMDA receptor antagonist MK-801 could antagonize the inhibitory effect of DA, D_1 agonist SKF 38393 and D_2 agonist LY 171555 on CCDPKⅡ activity. Both the D_1 antagonist SCH 23390 and the D_2 antagonist spiperone antagonized Glu-induced decrease of CCDPKⅡ activity. (2) DA and SKF 38393 significantly increased PKA activity in striatal slices, and MK-801 reduced this effect. (3) DA and Glu increase LDH release and are proportional to the concentration. MK-801 antagonized DA-induced increase in LDH release; spiperone significantly reduced Glu-induced LDH release in striatal neurons. Conclusion: The interaction between DA and Glu is very important for the regulation of CCDPKⅡand PKA activity and cell function in striatum neurons.