多巴胺诱导大鼠海马脑片Ca^(2+)-钙调素依赖性蛋白激酶Ⅱ活性的抑制作用(英文)

Inhibitory effect of dopamine on Ca^(2+) -calmodulin-dependent protein kinase Ⅱ activity in rat hippocampal slices

目的:研究多巴胺(DA)对大鼠海马脑片Ca^(2+)-钙调素依赖性蛋白激酶Ⅱ(CCDPK Ⅱ)活性的影响。方法:采用大鼠海马脑片体外培养模型,以^(32)P-掺入法测定CCDPK Ⅱ的活性。结果:外源性DA可显著降低大鼠海马脑片CCDPK Ⅱ活性,并有一定的浓度依赖性和时间依赖性。去除胞外的Ca^(2+)对不同浓度DA诱导的CCDPK Ⅱ活性抑制有部分或完全保护作用。阿扑吗啡(非特异性DA受体激动剂)、SKF38393(特异性D_1样DA受体激动剂)和喹吡罗(特异性D_2样DA受体激动剂)均可显著降低CCDPK Ⅱ的活性。Sch-23390(特异性D_1样DA受体拮抗剂)和多潘立酮(特异性D_2样DA受体拮抗剂)均可拮抗DA所诱导的酶活性抑制。结论:DA抑制海马CCDPK Ⅱ的活性,其作用机制与D_1样和D_2样受体以及胞外Ca^(2+)的内流有关。

AIM: To study the effect of dopamine (DA) on Ca2 + -calnaodulin dependent protein kinase Ⅱ (CCDPK Ⅱ ) activity in rat hippocampus. METHODS: Using rat hippocampal slices as an in vitro model, the activity of CCDPK Ⅱwas examined by the method of 32P-incorporation. RESULTS: Exogenous DA reduced CCDPK Ⅱ activity in hippocampal slices in a concentration- and time-dependent manner. Removal of extracellular calcium antagonized the DA-induced inhibition of CCDPK Ⅱ activity, partially or completely. The activity of CCDPK Ⅱwas markedly decreased by apomorphine (a nonselective DA receptor agonist), SKF38393 (a selective D1-like DA receptor agonist), or quinpirole (a selective D2-like DA receptor agonist). The inhibition of CCDPK Ⅱ activity induced by exogenous DA was abolished by preincubation with Sch-23390, a selective D1-like DA receptor antagonist, or domperidone, a selective D2-like DA receptor antagonist. CONCLUSION: DA has an inhibitory effect on CCDPK II activity in rat hippocampus, .related to stimulation of D1-like and D2-like receptors and calcium influx.