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目的 :研究多巴胺对血管平滑肌细胞大电流、钙激活钾 (BKca)通道的影响及其信息传递机制。方法 :用膜片钳细胞贴附式技术 ,记录细胞孵育液内灌流多巴胺受体激动剂、阻断剂以及第二信使及相关蛋白激酶拮抗剂对猪冠状动脉血管平滑肌细胞BKca通道活动的影响。结果 :多巴胺增加BKca通道活性 (P <0 .0 1 ) ;并可被DA 1受体阻断剂SCH2 3390完全阻断 ,但不受β2 受体阻断剂普萘洛尔的影响。腺苷酸环化酶抑制剂SQ2 2 5 36可完全阻断多巴胺的作用 ;而cAMP拟似剂CTP cAMP单独应用可增强BKCa通道的活性。蛋白激酶A的拮抗剂RP 8CTP cAMPs对多巴胺增强BKCa活性作用无影响。而蛋白激酶G的拮抗剂KT5 82 3完全阻断了多巴胺这一效应 (P <0 .0 1 )。结论 :多巴胺作用于DA 1受体增强猪冠状动脉血管平滑肌的BKCa活性是通过升高cAMP激活PKG引起的。
Objective: To study the effect of dopamine on high current and calcium-activated potassium (BKca) channels in vascular smooth muscle cells and its mechanism of information transmission. Methods: Patch-clamp technique was used to record the effects of perfusion dopamine receptor agonists, blockers, second messengers and related protein kinase antagonists on the activity of BKca channel in porcine coronary artery smooth muscle cells. RESULTS: Dopamine increased the activity of BKca channel (P <0.01) and was completely blocked by the DA1 receptor blocker SCH2 3390 but not by the β2 receptor blocker propranolol. Adenylate cyclase inhibitor SQ2 2 5 36 can completely block the action of dopamine; while cAMP cAMP analogue CTP cAMP alone can enhance the activity of BKCa channel. RP 8 CTP cAMPs, an antagonist of protein kinase A, had no effect on dopamine potentiation of BKCa activity. However, KT5 82 3, an antagonist of protein kinase G, completely blocked the effect of dopamine (P <0.01). CONCLUSION: Dopamine acts on DA 1 receptor and enhances BKCa activity in porcine coronary artery smooth muscle by elevating cAMP to activate PKG.