Intermedin enhances sympathetic outflow via receptor-mediated cAMP/PKA signaling pathway in nucleus tractus solitarii of rats
Intermedin enhances sympathetic outflow via receptor-mediated cAMP/PKA signaling pathway in nucleus tractus solitarii of rats
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Intermedin 通过受体介导的 cAMP/PKA 信号通路增强大鼠孤束核交感神经流出
DOI：
10.1016/j.peptides.2013.05.002
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发表时间：
2013-09-01
期刊：
影响因子：
3
通讯作者：
Zhou, Ye-Bo
中科院分区：
文献类型：
--
作者：
Li, Peng;Sun, Hai-Jian;Zhou, Ye-Bo
脑内直接给药可产生不同于全身给药的心血管效应。孤束核（NTS）是心血管活动的重要区域。本研究旨在探讨IMD对孤束核交感神经流出的调节作用及其相关的分子机制。记录麻醉大鼠肾交感神经活动（RSNA）和平均动脉压（MAP）。特定部位微量注射IMD（20 pmol）双侧进入NTS显着增加RSNA和MAP。用受体拮抗剂ADM 22 -52、腺苷酸环化酶（AC）抑制剂5 Q22536或蛋白激酶A（PKA）抑制剂Rp-cAMP预处理，几乎可以消除IMD引起的RSNA和MAP的增加。而另一种受体拮抗剂降钙素基因相关肽（CGRP）8-37预处理不能抑制IMD引起的RSNA和MAP的升高。此外，IMD增加环磷酸腺苷（cAMP）的水平，这是抑制ADM 22 -52预处理的NTS。这些结果表明，IMD参与了交感神经活动和心血管系统的中枢调节，受体介导的cAMP/PKA信号通路参与了IMD在NTS的诱导效应。(C)2013 Elsevier Inc. All rights reserved.
Direct administration of intermedin (IMD) into the brain elicits cardiovascular effects different from the systemic administration. Nucleus tractus solitarii (NTS) is an important region for the cardiovascular regulation. The present study was designed to determine the effect of IMD on modulating the sympathetic outflow and its related molecular mechanism in the NTS. Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded in anesthetized rats. Site-specific microinjection of IMD (20 pmol) bilaterally into the NTS significantly increased RSNA and MAP. IMD-evoked increases of RSNA and MAP were almost abolished by pretreatment with receptor antagonist ADM22-52, an adenylyl cyclase (AC) inhibitor 5Q22536, or a protein kinase A (PKA) inhibitor Rp-cAMP. However, pretreatment with another receptor antagonist calcitonin gene-related peptide (CGRP)8-37 did not suppress the increases of RSNA and MAP induced by IMD. Furthermore, IMD increased the cyclic adenosine monophosphate (cAMP) level, which was inhibited by ADM22-52 pretreatment in the NTS. These results suggest that IMD participates in the sympathetic nerve activity and central regulation of the cardiovascular system and a receptor-mediated cAMP/PKA signaling pathway is involved in IMD-induced effects in the NTS. (C) 2013 Elsevier Inc. All rights reserved.