首页> 外文期刊>The Korean Journal of Physiology & Pharmacology >Pituitary Adenylate Cyclase-activating Polypeptide Inhibits Pacemaker Activity of Colonic Interstitial Cells of Cajal
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Pituitary Adenylate Cyclase-activating Polypeptide Inhibits Pacemaker Activity of Colonic Interstitial Cells of Cajal

机译:垂体腺苷酸环化酶激活多肽抑制Cajal结肠间质细胞的起搏器活性。

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This study aimed to investigate the effect of pituitary adenylate cyclase-activating peptide (PACAP) on the pacemaker activity of interstitial cells of Cajal (ICC) in mouse colon and to identify the underlying mechanisms of PACAP action. Spontaneous pacemaker activity of colonic ICC and the effects of PACAP were studied using electrophysiological recordings. Exogenously applied PACAP induced hyperpolarization of the cell membrane and inhibited pacemaker frequency in a dose-dependent manner (from 0.1 nM to 100 nM). To investigate cyclic AMP (cAMP) involvement in the effects of PACAP on ICC, SQ-22536 (an inhibitor of adenylate cyclase) and cell-permeable 8-bromo-cAMP were used. SQ-22536 decreased the frequency of pacemaker potentials, and cell-permeable 8-bromo-cAMP increased the frequency of pacemaker potentials. The effects of SQ-22536 on pacemaker potential frequency and membrane hyperpolarization were rescued by co-treatment with glibenclamide (an ATP-sensitive K+ channel blocker). However, neither N G-nitro-L-arginine methyl ester (L-NAME, a competitive inhibitor of NO synthase) nor 1 H -[1,2,4]oxadiazolo[4,3-α]quinoxalin-1-one (ODQ, an inhibitor of guanylate cyclase) had any effect on PACAP-induced activity. In conclusion, this study describes the effects of PACAP on ICC in the mouse colon. PACAP inhibited the pacemaker activity of ICC by acting through ATP-sensitive K+ channels. These results provide evidence of a physiological role for PACAP in regulating gastrointestinal (GI) motility through the modulation of ICC activity.
机译:这项研究旨在调查垂体腺苷酸环化酶激活肽(PACAP)对小鼠结肠Cajal间质细胞(ICC)的起搏器活性的影响,并确定PACAP作用的潜在机制。使用电生理记录研究了结肠ICC的自发起搏器活性和PACAP的作用。外源施加的PACAP诱导细胞膜超极化,并以剂量​​依赖性方式(从0.1 nM到100 nM)抑制起搏器频率。为了研究环AMP(cAMP)参与PACAP对ICC的影响,使用了SQ-22536(腺苷酸环化酶抑制剂)和可渗透细胞的8-溴-cAMP。 SQ-22536降低了起搏器电位的频率,而可渗透细胞的8-溴-cAMP增加了起搏器电位的频率。 SQ-22536对起搏器电位频率和膜超极化的影响通过与格列本脲(一种ATP敏感的K + 通道阻滞剂)共同处理得以挽救。但是,N G -硝基-L-精氨酸甲酯(L-NAME,NO合酶的竞争性抑制剂)和1 H-[1,2,4]恶二唑[4,3-α]均不存在。 ] quinoxalin-1-one(ODQ,鸟苷酸环化酶抑制剂)对PACAP诱导的活性没有任何影响。总之,这项研究描述了PACAP对小鼠结肠ICC的影响。 PACAP通过ATP敏感的K + 通道抑制ICC的起搏器活性。这些结果提供了PACAP通过调节ICC活性来调节胃肠(GI)运动的生理作用的证据。

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