Wang Y Y, Aghajanian G K
Department of Pharmacology, School of Medicine, Yale University, New Haven, Connecticut.
J Neurosci. 1990 Oct;10(10):3335-43. doi: 10.1523/JNEUROSCI.10-10-03335.1990.
In accord with previous studies, it was found that vasoactive intestinal peptide (VIP), a powerful activator of adenylate cyclase, and cAMP-active agents (i.e., 8-Br-cAMP, forskolin, and Ro20-1724) increased the firing rate of noradrenergic neurons in the locus coeruleus (LC) by inducing an inward current. The response to VIP was usually more rapid and larger in a subpopulation of LC neurons with subthreshold rhythmic oscillations in membrane potential (oscillatory cells) as compared to nonoscillatory cells. In either case, the inward currents elicited by VIP and cAMP-active agents were found to be nonadditive, suggesting the action of VIP, at least in part, is via the same mechanism as that of cAMP-active agents. Intracellular application of a specific protein (or related peptide) inhibitor of cAMP-dependent protein kinase markedly attenuated the activation induced by either cAMP-active agents or VIP, suggesting that cAMP-dependent protein kinase (protein kinase A), presumably through protein phosphorylation, plays a role in the action of VIP. Taken together, the results provide evidence that cAMP and protein kinase A are involved in mediating the electrophysiological actions of VIP on LC neurons.
与先前的研究一致，发现血管活性肠肽（VIP），一种腺苷酸环化酶的强力激活剂，以及cAMP活性剂（即8-溴-cAMP、福斯可林和Ro20-1724）通过诱导内向电流增加了蓝斑（LC）中去甲肾上腺素能神经元的放电率。与非振荡细胞相比，在膜电位具有阈下节律性振荡的LC神经元亚群（振荡细胞）中，对VIP的反应通常更快且更大。在任何一种情况下，发现VIP和cAMP活性剂引起的内向电流是不可加的，这表明VIP的作用至少部分是通过与cAMP活性剂相同的机制。细胞内应用cAMP依赖性蛋白激酶的特异性蛋白（或相关肽）抑制剂显著减弱了cAMP活性剂或VIP诱导的激活，表明cAMP依赖性蛋白激酶（蛋白激酶A）可能通过蛋白磷酸化在VIP的作用中发挥作用。综上所述，这些结果提供了证据，表明cAMP和蛋白激酶A参与介导VIP对LC神经元的电生理作用。
