Cui M, Nicol G D
Department of Pharmacology & Toxicology, School of Medicine, Indiana University, Indianapolis 46202-5126, USA.
Neuroscience. 1995 May;66(2):459-66. doi: 10.1016/0306-4522(94)00567-o.
Prostaglandins enhance the sensitivity of sensory neurons to excitatory chemical agents such as bradykinin. The intracellular transduction cascades mediating this potentiation remain largely unknown. We have examined the role of cyclic AMP in the prostaglandin E2-induced potentiation of sensory neurons. Pretreatment with agents that elevate intracellular cyclic AMP levels enhances the number of action potentials elicited by bradykinin in a manner analogous to that of prostaglandin E2. The prostaglandin E2-induced potentiation of the number of bradykinin-elicited action potentials is blocked by either inhibition of adenylyl cyclase or protein kinase A. Therefore, our results suggest that prostaglandin E2 activates adenylyl cyclase to increase intracellular cyclic AMP, which in turn activates protein kinase A. Presumably activation of protein kinase A leads to increased levels of protein phosphorylation that then contribute to the enhancement of neuronal sensitivity to excitatory chemical agents.
前列腺素可增强感觉神经元对诸如缓激肽等兴奋性化学物质的敏感性。介导这种增强作用的细胞内转导级联反应在很大程度上仍不清楚。我们研究了环磷酸腺苷（cAMP）在前列腺素E2诱导的感觉神经元增强作用中的作用。用能提高细胞内环磷酸腺苷水平的试剂进行预处理，能以类似于前列腺素E2的方式增强缓激肽引发的动作电位数量。前列腺素E2诱导的缓激肽引发的动作电位数量的增强作用，可通过抑制腺苷酸环化酶或蛋白激酶A来阻断。因此，我们的结果表明，前列腺素E2激活腺苷酸环化酶以增加细胞内环磷酸腺苷，进而激活蛋白激酶A。据推测，蛋白激酶A的激活导致蛋白质磷酸化水平升高，进而有助于增强神经元对兴奋性化学物质的敏感性。
