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首页> 外文期刊>Life sciences >Involvement of protein kinase C in the adaptive changes of cholinergic neurons to sympathetic denervation in the guinea pig myenteric plexus.
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Involvement of protein kinase C in the adaptive changes of cholinergic neurons to sympathetic denervation in the guinea pig myenteric plexus.

机译：蛋白激酶C参与豚鼠肌间神经丛中胆碱能神经元对交感神经的适应性改变。

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Supersensitivity to muscarinic, kappa- and mu-opioid agents modulating cholinergic neurons in the guinea pig colon develops after chronic sympathetic denervation. A possible role for protein kinase C (PKC) in contributing to development of these sensitivity changes was investigated. The PKC activator, phorbol-12-myristate-13-acetate (PMA), enhanced acetylcholine (ACh) overflow in preparations obtained from normal animals. The facilitatory effect of PMA was significantly reduced after prolonged exposure to the phorbol ester and by the PKC inhibitors, chelerythrine and calphostin C. Subsensitivity to the facilitatory effect of PMA developed after chronic sympathetic denervation. In this experimental condition, immunoblot analysis revealed reduced levels of PKC in myenteric plexus synaptosomes. The facilitatory effect of the muscarininc antagonist, scopolamine, on ACh overflow was significantly reduced by the phospolipase C (PLC) inhibitor, U73122, chelerythrine and calphostin C, both in normal and denervated animals. However, in both experimental groups, PLC antagonists and PKC antagonists did not affect the inhibitory effect of the muscarinic agonist, oxotremorine-M on ACh overflow. The inhibitory effects of U69593 (kappa-opioid receptor agonist) and DAMGO (mu-opioid receptor agonist) on ACh overflow significantly increased in the presence of U73122, chelerythrine and calphostin C in preparations obtained from normal animals, but not in those obtained from sympathetically denervated animals.These results indicate that activation of PKC enhances ACh release in the myenteric plexus of the guinea pig colon. At this level, chronic sympathetic denervation entails a reduced efficiency of the enzyme. In addition, PKC is involved in the inhibitory modulation of ACh release mediated by muscarinic-, kappa- and mu-opioid receptors, although with different modalities. Muscarinic receptors inhibit PKC activity, whereas kappa- and mu-opioid receptors increase PKC activity. Both the inhibitory and the facilitatory effect on PKC involve modulation of PLC activity. The possibility that the change in PKC activity represents one of the biochemical mechanisms at the basis of development of sensitivity changes to opioid and muscarinic agents after chronic sympathetic denervation is discussed.
机译：慢性交感神经去神经后，对调节豚鼠结肠胆碱能神经元的毒蕈碱，κ和μ阿片类药物产生超敏反应。研究了蛋白激酶C（PKC）在促进这些敏感性变化中的可能作用。从正常动物获得的制剂中，PKC激活剂佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）增强了乙酰胆碱（ACh）的溢出。长时间暴露于佛波酯和PKC抑制剂白屈菜红碱和钙磷蛋白C后，PMA的促进作用明显降低。慢性交感神经去神经后，对PMA的促进作用的敏感性降低。在这种实验条件下，免疫印迹分析表明，肌间神经丛突触小体中的PKC水平降低。在正常和非神经支配动物中，磷磷脂酶C（PLC）抑制剂U73122，白屈菜红碱和钙磷蛋白C均显着降低了毒蕈碱拮抗剂东pol碱对ACh的促进作用。但是，在两个实验组中，PLC拮抗剂和PKC拮抗剂均不影响毒蕈碱激动剂oxotremorine-M对ACh溢出的抑制作用。在正常动物获得的制剂中存在U73122，白屈菜红碱和钙磷蛋白C的情况下，U69593（κ阿片受体激动剂）和DAMGO（μ阿片受体激动剂）对ACh溢流的抑制作用显着增强，但在同情动物获得的制剂中则没有这些结果表明PKC的激活增强了豚鼠结肠肌间神经丛中ACh的释放。在这个水平上，慢性交感神经去神经导致酶效率降低。此外，PKC参与了由毒蕈碱受体，κ受体和μ阿片受体介导的ACh释放的抑制性调节，尽管其方式不同。毒蕈碱受体抑制PKC活性，而kappa和mu阿片受体增加PKC活性。对PKC的抑制和促进作用均涉及PLC活性的调节。讨论了PKC活性变化代表慢性交感神经去神经后对阿片类药物和毒蕈碱类药物敏感性变化的基础上的生化机制之一的可能性。

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