SKF38393抑制大鼠DRG分离神经元ATP-激活电流  

Inhibition by SKF38393 of ATP-activated current in rat DRG neurons

作　　者：李国华[1] 王新均[1] 何华琼[1] 郑先科[1] 李之望[2] 

机构地区：[1]郧阳医学院机能实验室,湖北十堰442000 [2]华中科技大学同济医学院实验医学研究中心

出　　处：《郧阳医学院学报》2003年第3期129-132,137,共5页Journal of Yunyang Medical College

基　　金：国家自然科学基金 (No .3 9970 2 40 );湖北省教育厅研究基金 ( 2 0 0 2X96)资助项目

摘　　要：目的 :探讨多巴胺D1受体的选择性激动剂SKF3 83 93HCl对ATP -激活电流的作用。方法 :在大鼠新鲜分离的DRG神经元标本上应用全细胞膜片钳技术 ,记录SKF3 83 93对ATP -激活电流的作用。结果 :大部分受检细胞 ( 87.5% ,77/ 88)对ATP敏感 ,10 - 6 ～ 10 - 3 mol/LATP可引起剂量依赖性呈明显去敏感的内向电流。在此77个细胞中 ,预加SKF3 83 93可引起三类反应 :①外向电流 ( 7.8% ,6/ 77) ;②内向电流 ( 2 6.0 % ,2 0 / 77) ;③无反应( 66.2 % ,51/ 77)。与ATP -激活电流相比 ,SKF3 83 93 -激活电流幅值小 ,无明显去敏感现象。预加SKF3 83 93 3 0～ 60s对ATP -激活电流的影响如下 :在 74.0 % ( 57/ 77)的细胞产生抑制作用 ,15.6% ( 12 / 77)的细胞产生增强作用 ,其余的无明显作用 ( 10 .4% ,8/ 77) ,本文主要针对此抑制作用进行探讨。此种抑制作用与SKF3 83 93本身是否引起或引起的是内向或外向电流无关。在浓度 10 - 9～ 10 - 4mol/L范围SKF3 83 93对 10 - 4mol/LATP -激活电流的抑制作用依赖于SKF3 83 93的浓度。胞内透析H 7上述抑制作用可完全被取消 ,而胞内透析H9此抑制作用依旧存在。结论 :SKF3 83 93对ATP -激活电流的抑制作用可能是由于D1受体激活后经G蛋白偶联及PKC途径使ATP受体磷酸化所致。Objective The purpose of the present s tudy was to explore whether SKF38393 modulates the response mediated by ATP(P2X) receptors. Methods Experiments were performed on neuron s freshly isolated from rat DRG using whole-cell patch clamp techniques. Results The majority of the neurons examined were responsive to ATP (87.5%,77/88) in the concentration range from 10 -6 to 10 -3 mol/ L with an inward current showing obvious desensitization. In the 77 ATP-sensitiv e cells, responses induced by selective agonist of dopamine D 1 receptor SKF38 393 manifested three patterns:①outward current(7.8%,6/77);②inward current(2 6.0%,20/77) and no detectable response(66.2%,51/77). Compared with ATP-activat ed current, the SKF38393-activated current was of smaller amplitude and showed unapparent desensitization. When the neurons were treated with SKF38393 prior to application of ATP for 30～60 s, the ATP-activated current in the majority of t he cells 74.0%(57/77) was inhibited,15.6%(12/77) was increased,while the remai ning cells(10.4%,8/77)was not affected ,The purpose of this paper was to explo re the inhibitory action. The effect of SKF38393 was dose dependent(10 -9 ～ 1 0 -4 mol/L). By intracellular dialysis of H7 the inhibitory effect of SKF38 393 could be completely abolished,but intracellular dialysis of H9 the inhibito ry effect of SKF38393 could not be abolished. Conclusions Suggesting this inhibitory action might be an outcome of the phosphorylation of ATP receptor resulting from intracellular signal transduction.

关 键 词：SKF38393 抑制 大鼠 DRG 分离 神经元 ATP-激活电流 

分 类 号：R338.8[医药卫生—人体生理学]