A possible role for phospholipase A(2) in the action of general anesthetics
A possible role for phospholipase A(2) in the action of general anesthetics
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DOI：
10.1152/ajpcell.1996.270.2.c636
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发表时间：
1996-02-01
影响因子：
5.5
通讯作者：
Eaton, DC
中科院分区：
文献类型：
--
作者：
Denson, DD;Worrell, RT;Eaton, DC
全麻在临床相关浓度下抑制Ca2+活化钾（BK）通道。本研究考察了全身麻醉剂通过破坏磷脂酶A(2) (PLA(2))-花生四烯酸信号转导通路而对BK通道产生影响的可能性。外源性花生四烯酸（2.5 μ M）处理切除的斑块导致BK通道活性增加3.6 +/- 1.3倍。随后将这些斑块暴露于浓度为氟烷（0.6 mM）、氯胺酮（100 μ M）或依托咪酯（10 μ M）的环境中，在没有花生四烯酸的情况下，这些物质通常会阻断60-80%的通道，但并未降低通道活性。花生四烯酸使氯胺酮剂量-反应曲线的50%有效浓度从3.4 +/- 0.4显著提高到693 +/- 379 μ M (P < 0.001)，斜率从1.40 +/- 0.21显著降低到0.59 +/- 0.05 （P < 0.001）。PLA(2)抑制剂醌（1 μ M）、马兜铃酸（250 μ M）和十八烷基苯甲酰丙烯酸（7 μ M）对BK通道的抑制作用分别为61 +/- 6%、47 +/- 2%和30 +/- 9%，其抑制作用与全身麻醉剂的抑制作用难以区分。马兜铃酸和氯胺酮显著抑制PLA(2)介导的花生四烯酸在GH(3)细胞中的产生。
General anesthetics inhibit Ca2+-activated potassium (BK) channels at clinically relevant concentrations. This study examined the possibility that general anesthetics produce their effect on BK channels by disrupting the phospholipase A(2) (PLA(2))-arachidonic acid signal transduction pathway. Treatment of excised patches with exogenous arachidonic acid (2.5 mu M) resulted in a 3.6 +/- 1.3-fold increase in BK channel activity. Subsequent exposure of these patches to concentrations of halothane (0.6 mM), ketamine (100 mu M), or etomidate (10 mu M) that would normally block the channel by similar to 60-80% in the absence of arachidonic acid did not reduce the channel activity. Arachidonic acid resulted in a significant increase in the 50% effective concentration for the ketamine dose-response curve from 3.4 +/- 0.4 to 693 +/- 379 mu M (P < 0.001) as well as a significant decrease in slope from 1.40 +/- 0.21 to 0.59 +/- 0.05 (P < 0.001). The PLA(2) inhibitors quinacrine (1 mu M), aristolochic acid (250 mu M), and octadecylbenzoylacrylic acid (7 mu M) inhibited BK channels by 61 +/- 6, 47 +/- 2, and 30 +/- 9%, respectively, and in a manner indistinguishable from general anesthetics inhibition. Aristolochic acid and ketamine significantly inhibit the PLA(2)-mediated production of arachidonic acid in GH(3) cells.