Li Li-Sheng, Liu Chen-Zhe, Xu Jing-Dong, Zheng Li-Fei, Feng Xiao-Yan, Zhang Yue, Zhu Jin-Xia
Li-Sheng Li, Chen-Zhe Liu, Jing-Dong Xu, Li-Fei Zheng, Xiao-Yan Feng, Yue Zhang, Jin-Xia Zhu, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
World J Gastroenterol. 2015 Mar 28;21(12):3509-18. doi: 10.3748/wjg.v21.i12.3509.
To study the effects of entacapone, a catechol-O-methyltransferase inhibitor, on colon motility and electrolyte transport in Parkinson's disease (PD) rats.
Distribution and expression of catechol-O-methyltransferase (COMT) were measured by immunohistochemistry and Western blotting methods. The colonic smooth muscle motility was examined in vitro by means of a muscle motility recording device. The mucosal electrolyte transport of PD rats was examined by using a short-circuit current (ISC ) technique and scanning ion-selective electrode technique (SIET). Intracellular detection of cAMP and cGMP was accomplished by radioimmunoassay testing.
COMT was expressed in the colons of both normal and PD rats, mainly on the apical membranes of villi and crypts in the colon. Compared to normal controls, PD rats expressed less COMT. The COMT inhibitor entacapone inhibited contraction of the PD rat longitudinal muscle in a dose-dependent manner. The β2 adrenoceptor antagonist ICI-118,551 blocked this inhibitory effect by approximately 67% (P < 0.01). Entacapone increased mucosal ISC in the colon of rats with PD. This induction was significantly inhibited by apical application of Cl(-) channel blocker diphenylamine-2, 2'-dicarboxylic acid, basolateral application of Na(+)-K(+)-2Cl(-)co-transporter antagonist bumetanide, elimination of Cl(-) from the extracellular fluid, as well as pretreatment using adenylate cyclase inhibitor MDL12330A. As an inhibitor of prostaglandin synthetase, indomethacin can inhibit entacapone-induced ISC by 45% (P < 0.01). When SIET was applied to measure Cl(-) flux changes, this provided similar results. Entacapone significantly increased intracellular cAMP content in the colonic mucosa, which was greatly inhibited by indomethacin.
COMT expression exists in rat colons. The β2 adrenoceptor is involved in the entacapone-induced inhibition of colon motility. Entacapone induces cAMP-dependent Cl(-) secretion in the PD rat.
研究儿茶酚-O-甲基转移酶抑制剂恩他卡朋对帕金森病（PD）大鼠结肠动力和电解质转运的影响。
采用免疫组织化学和蛋白质印迹法检测儿茶酚-O-甲基转移酶（COMT）的分布和表达。通过肌肉动力记录装置在体外检测结肠平滑肌动力。采用短路电流（ISC）技术和扫描离子选择性电极技术（SIET）检测PD大鼠的黏膜电解质转运。通过放射免疫分析检测细胞内cAMP和cGMP。
COMT在正常大鼠和PD大鼠的结肠中均有表达，主要位于结肠绒毛和隐窝的顶端膜上。与正常对照组相比，PD大鼠的COMT表达较少。COMT抑制剂恩他卡朋以剂量依赖性方式抑制PD大鼠纵肌收缩。β2肾上腺素能受体拮抗剂ICI-118,551可阻断这种抑制作用约67%（P<0.01）。恩他卡朋增加了PD大鼠结肠黏膜的ISC。顶端应用Cl(-)通道阻滞剂二苯胺-2,2'-二羧酸、基底外侧应用Na(+)-K(+)-2Cl(-)共转运体拮抗剂布美他尼、从细胞外液中去除Cl(-)以及使用腺苷酸环化酶抑制剂MDL12330A预处理均显著抑制了这种诱导作用。作为前列腺素合成酶抑制剂，吲哚美辛可抑制恩他卡朋诱导的ISC达45%（P<0.01）。当应用SIET测量Cl(-)通量变化时，结果相似。恩他卡朋显著增加结肠黏膜细胞内cAMP含量，吲哚美辛可显著抑制该作用。
大鼠结肠中存在COMT表达。β2肾上腺素能受体参与恩他卡朋诱导的结肠动力抑制。恩他卡朋诱导PD大鼠cAMP依赖性Cl(-)分泌。
