Gherghina Florin Liviu, Tica Andrei Adrian, Deliu Elena, Abood Mary E, Brailoiu G Cristina, Brailoiu Eugen
Department of Pharmacology, University of Medicine and Pharmacy, Craiova, Romania.
Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Brain Res. 2017 Feb 15;1657:297-303. doi: 10.1016/j.brainres.2016.12.026. Epub 2016 Dec 30.
The pituitary adenylyl cyclase-activating polypeptide (PACAP) and its G protein-coupled receptors, PAC1, VPAC1 and VPAC2 form a system involved in a variety of biological processes. Although some sympathetic stimulatory effects of this system have been reported, its central cardiovascular regulatory properties are poorly characterized. VPAC1 receptors are expressed in the nucleus ambiguus (nAmb), a key center controlling cardiac parasympathetic tone. In this study, we report that selective VPAC1 activation in rhodamine-labeled cardiac vagal preganglionic neurons of the rat nAmb produces inositol 1,4,5-trisphosphate receptor-mediated Ca mobilization, membrane depolarization and activation of P/Q-type Ca channels. In vivo, this pathway converges onto transient reduction in heart rate of conscious rats. Therefore we demonstrate a VPAC1-dependent mechanism in the central parasympathetic regulation of the heart rate, adding to the complexity of PACAP-mediated cardiovascular modulation.
垂体腺苷酸环化酶激活多肽（PACAP）及其G蛋白偶联受体PAC1、VPAC1和VPAC2构成了一个参与多种生物过程的系统。尽管已经报道了该系统的一些交感神经刺激作用，但其中枢心血管调节特性却鲜有描述。VPAC1受体在疑核（nAmb）中表达，疑核是控制心脏副交感神经张力的关键中枢。在本研究中，我们报告称，在大鼠nAmb中用罗丹明标记的心脏迷走神经节前神经元中选择性激活VPAC1会产生肌醇1,4,5 - 三磷酸受体介导的钙动员、膜去极化以及P/Q型钙通道的激活。在体内，该途径会导致清醒大鼠心率短暂降低。因此，我们证明了在心率的中枢副交感神经调节中存在一种依赖VPAC1的机制，这增加了PACAP介导的心血管调节的复杂性。
