Carbachol inhibits Na+-K+-ATPase activity in choroid plexus via stimulation of the NO/cGMP pathway
Carbachol inhibits Na+-K+-ATPase activity in choroid plexus via stimulation of the NO/cGMP pathway
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DOI：
10.1152/ajpcell.2000.279.6.c1685
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发表时间：
2000-12-01
影响因子：
5.5
通讯作者：
Sweadner, KJ
中科院分区：
文献类型：
--
作者：
Ellis, DZ;Nathanson, JA;Sweadner, KJ
脉络丛的胆碱能神经支配可抑制脑脊液的分泌。我们证实了卡巴胆碱对牛脉络膜组织切片中Na~+-K~+-ATPase的抑制作用，并探讨了其作用机制。胆碱能药物的许多作用是由一氧化氮(NO)介导的，一氧化氮在液体内稳态中起着重要作用。NO合酶抑制剂[N-奥米伽-硝基-L-精氨酸甲酯]阻断Na+-K+-ATPase的抑制作用，并被NO激动剂硝普钠和二乙烯三胺NO定量模拟。SNP的抑制作用与组织cGMP的增加有关，并可被可溶性鸟苷环化酶抑制剂H-1-[1，2，4]恶二唑并[4，3-a]喹恶灵-1-酮所消除。蛋白激酶G激活剂8-溴-cGMP和蛋白磷酸酶1和2A的抑制剂冈田酸模拟抑制作用。依赖cGMP的蛋白激酶抑制剂RP-8-PCPT-cGMP(0.5-5um)和KT-5823(2.0 mM)不能阻断SNP的作用，但较高浓度的选择性抑制剂(RP-8-PCPT-cGMP)对Na+-K+-ATPase有药理抑制作用。提示Na+-K+-ATPase的胆碱能调节是由NO介导的，涉及鸟苷环化酶的激活和cGMP的升高。
Secretion of cerebrospinal fluid by the choroid plexus can be inhibited by its cholinergic innervation. We demonstrated that carbachol inhibits the Na+ -K+-ATPase in bovine choroid tissue slices and investigated the mechanism. Many of the actions of cholinergic agents are mediated by nitric oxide (NO), which plays important roles in fluid homeostasis. The inhibition of Na+-K+-ATPase was blocked by the NO synthase inhibitor [N-omega-nitro-L-arginine methyl ester] and was quantitatively mimicked by the NO agonists sodium nitroprusside (SNP) and diethylenetriamine NO. Inhibition by SNP correlated with an increase in tissue cGMP and was abolished by H-1-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one, an inhibitor of soluble guanylate cyclase. Inhibition was mimicked by the protein kinase G activator 8-bromo-cGMP and by okadaic acid, an inhibitor of protein phosphatases 1 and 2A. cGMP-dependent protein kinase inhibitors Rp-8-pCPT-cGMP (0.5-5 muM) and KT-5823 (2.0 mM) did not block the effects of SNP, but higher concentrations of the more selective inhibitor (Rp-8-pCPT-cGMP) had a pharmacological inhibitory effect on Na+-K+-ATPase. The data suggest that cholinergic regulation of the Na+-K+-ATPase is mediated by NO and involves activation of guanylate cyclase and elevation of cGMP.