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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。
Objective: To study the effect of dopamine on the activity of Ca ~ (2 +) - calmodulin dependent protein kinase Ⅱ (CCDPK Ⅱ) in rat hippocampal slices. Methods: Rat hippocampal slices were cultured in vitro and the activity of CCDPK Ⅱ was determined by ~ (32) P-incorporation method. Results: Exogenous DA can significantly reduce CCDPK Ⅱ activity in rat hippocampal slices, and have a concentration-dependent and time-dependent manner. Removal of extracellular Ca ~ (2+) has some or complete protective effect on the inhibition of CCDPK Ⅱ activity induced by different concentrations of DA. Apomorphine (a nonspecific DA receptor agonist), SKF38393 (a specific Dl-like DA receptor agonist) and quinpirone (a specific D? -like DA receptor agonist) all significantly reduced CCDPK II activity. Both Sch-23390 (specific Dl-like DA receptor antagonist) and domperidone (specific D_2-like DA receptor antagonist) antagonized the inhibition of DA induced enzyme activity. CONCLUSION: DA inhibits the activity of CCDPK Ⅱ in the hippocampus and its mechanism is related to the influx of D_1 -like and D_2-like receptors and extracellular Ca ~ (2+).