Ellis D Z, Nathanson J A, Sweadner K J
Neuroscience Center, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA.
Am J Physiol Cell Physiol. 2000 Dec;279(6):C1685-93. doi: 10.1152/ajpcell.2000.279.6.C1685.
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 1H-[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 microM) and KT-5823 (2.0 microM) 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.
脉络丛对脑脊液的分泌可受其胆碱能神经支配的抑制。我们证明了卡巴胆碱可抑制牛脉络丛组织切片中的钠钾ATP酶，并对其机制进行了研究。胆碱能药物的许多作用是由一氧化氮（NO）介导的，NO在液体稳态中起重要作用。钠钾ATP酶的抑制作用被NO合酶抑制剂[N（ω）-硝基-L-精氨酸甲酯]阻断，并且可被NO激动剂硝普钠（SNP）和二乙三胺NO定量模拟。SNP的抑制作用与组织cGMP的增加相关，并被可溶性鸟苷酸环化酶的抑制剂1H-[1,2,4]恶二唑并[4,3-a]喹喔啉-1-酮消除。抑制作用被蛋白激酶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。cGMP依赖性蛋白激酶抑制剂Rp-8-pCPT-cGMP（0.5 - 5 microM）和KT-5823（2.0 microM）并未阻断SNP的作用，但更高浓度的更具选择性的抑制剂（Rp-8-pCPT-cGMP）对钠钾ATP酶有药理抑制作用。数据表明，钠钾ATP酶的胆碱能调节是由NO介导的，涉及鸟苷酸环化酶的激活和cGMP的升高。
