Dopamine-glutamate interaction in rat striatal slices: changes of CCDPKⅡ, PKA, and LDH activity by receptor-mediated mecha-nisms  

多巴胺和谷氨酸在纹状体脑片的相互作用:受体机制介导的CCDPKⅡ,PKA和LDH活性变化(英文)

作　　者：唐放鸣[1] 孙亚锋[1] 王然[1] 丁允闽 张光毅[1] 金国章 

机构地区：[1]徐州医学院生物化学与分子生物学研究中心,徐州221002 [2]中国科学院上海药物研究所

出　　处：《Acta Pharmacologica Sinica》2000年第2期51-56,共6页中国药理学报（英文版）

基　　金：Project supported by the Provincial Natural Science Foundation of Jiangsu, No BK97153;the Natural Science Foundation of Education Committee of Jiangsu Province, No 98KJB310005.

摘　　要：AIM: To study the effects of dopamine (DA) and gluta-mate (Glu) and their receptor agonists/antagonists on Ca2+ /calmodulin-dependent protein kinase Ⅱ (CCDPK Ⅱ), cyclic AMP-dependent protein kinase A (PKA) activities and the LDH release in rat striatal slices, and to examine the interaction between DA and Glu transmitter systems in striatum. METHODS: The activities of CCDPKⅡ , PKA, and the release of LDH were determined with the 32 P-incorporation and colorimetry respectively in rat striatal slices. RESULTS: (Ⅰ) Exogenous DA, D1 receptor agonist SKF 38393 and D2 receptor agonist LY 171555 reduced CCDPK Ⅱ activity in striatal slices; Glu also inhibited CCPPKⅡ activity in a concentration-dependent manner. NMDA receptor antagonist MK-801 could antagonize the inhibitory effect of SKF 38393 and LY 171555 on the CCDPK Ⅱ activity. D1 and D2 receptor antagonists SCH 23390 and spiperone could also antagonize the decrease of CCDPK Ⅱ activity induced by Glu; (2) DA and SKF 38393 markedly increased PKA activity in striatal slices, which was reduced by MK-801; (3) DA and Glu increased the release of LDH from the striatal neurons in a concentration-dependent manner. MK-801 antagonized the increase of LDH induced by DA. Spiperone, rather than SCH 23390, could reduce the release of LDH from striatal neuron in the presence of Glu. CONCLUSION: The interaction between DA and Glu transmitter systems is found in the regulation of the CCDPK Ⅱ and PKA activities and cell function in the striatum.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。

关 键 词：DOPAMINE GLUTAMATES dopamine receptors N-methyl-D-aspartate receptors corpus stria-turn Ca2+-calmodulin dependent protein kinase cyclic AMP-dependent protein kinases lactate dehydrogenase 

分 类 号：R96[医药卫生—药理学]