cGMP-PDE3-cAMP signal pathway involved in the inhibitory effect of CNP on gastric motility in rat

cGMP-PDE3-cAMP signal pathway involved in the inhibitory effect of CNP on gastric motility in rat
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cGMP-PDE3-cAMP信号通路参与CNP对大鼠胃动力的抑制作用

DOI:
10.1016/j.regpep.2012.11.001
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发表时间:
2013-01-10
影响因子:
--
通讯作者:
Xu, Wen-Xie
Xu, Wen-Xie
中科院分区:
其他
文献类型:
--
作者:
Cai, Ying-Lan;Sun, Qian;Xu, Wen-Xie

文献摘要

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本研究采用器官浴法和ELISA法研究C型利钠肽(CNP)抑制大鼠胃窦平滑肌自发收缩的机制,以阐明CNP-NPR-B/pGC-cGMP下游信号转导通路。CNP可显著降低胃窦平滑肌的自发收缩幅度,增加胃窦平滑肌组织中cGMP和cAMP的含量。在存在非选择性磷酸二酯酶(PDE)抑制剂IBMX的情况下,CNP对自发收缩的抑制作用被显著抑制;然而,CNP仍然增加cGMP的产生,而不是cAMP。PDE 2抑制剂EHNA对CNP引起的胃平滑肌收缩抑制和cGMP、cAMP生成增加无影响,而PDE 3抑制剂米力农与IBMX相似,可减弱CNP引起的胃平滑肌自发收缩抑制作用,增加cGMP含量,但不增加cAMP含量。提示cGMP-PDE 3-cAMP信号通路也参与了CNP对大鼠胃运动的抑制作用。(C)2012爱思唯尔有限公司版权所有。
In the present study, we investigated the mechanism of C-type natriuretic peptide (CNP)-induced inhibitory effect on spontaneous contraction of gastric antral smooth muscle to clarify CNP-NPR-B/pGC-cGMP downstream signal transduction pathway using organ bath and ELISA methods in rat. CNP significantly reduced the amplitude of the spontaneous contraction and increased the contents of cGMP and cAMP in the gastric antral smooth muscle tissue. In the presence of IBMX, a non-selective phosphodiesterase (PDE) inhibitor, the inhibitory effect of CNP on spontaneous contraction was significantly suppressed; however, the production of cGMP but not cAMP was still increased by CNP. EHNA, a PDE2 inhibitor, did not affect both CNP-induced inhibition of the contraction and CNP-induced increase of cGMP and cAMP generations in gastric smooth muscle tissue, while milrinone, a PDE3 inhibitor, similar to IBMX, attenuated the CNP-induced inhibitory effect on spontaneous contraction and increased the content of cGMP but not CAMP. The results suggest that cGMP-PDE3-cAMP signal pathway is also involved in the CNP-induced inhibition of gastric motility in rat. (C) 2012 Elsevier B.V. All rights reserved.