Xu Long, Lv Nonghua, Zhu Xuan, Chen Youxiang, Yang Jing
Department of gastroenterology, the First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China.
Eur J Pharmacol. 2009 Aug 1;615(1-3):171-6. doi: 10.1016/j.ejphar.2009.04.045. Epub 2009 May 3.
Emodin is a natural anthraquinone in rhubarb. It has been identified as a prokinetic drug for gastrointestinal motility in Chinese traditional medicine. Emodin contracts smooth muscle by increasing the concentration of intracellular Ca(2+). In many smooth muscles, increasing intracellular Ca(2+) activates Ca(2+)-activated Cl(-) channels (ClCA). The study was aimed to investigate the effects of emodin on ClCA channels in colonic smooth muscle. 4 channel physiology signal acquire system was used to measure isometric contraction of smooth muscle strips. ClCA currents were recorded by EPC10 with perforated whole cell model. Emodin contracted strips and cells in colonic smooth muscle and augmented ClCA currents. Niflumic acid (NFA) and 4', 4'-diisothiostilbene-2, 2-disulfonic acid (DIDS) blocked the effects. Gi/Go protein inhibits protein kinase A (PKA) and protein kinase C (PKC), and PKA and PKC reduced ClCA currents. Pertussis toxin (PTX, a special inhibitor of Gi/Go protein), 8-bromoadenosine 38, 58-cyclic monophosphate (8-BrcAMP, a membrane-permeant protein kinase A activator) and Phorbol-12-myristate-13-acetate (PMA, a membrane-permeant protein kinase C activator) inhibited the effects on ClCA currents significantly. Our findings suggest that emodin augments ClCA channels to contract smooth muscle in colon, and the effect is induced mostly by enhancement of membrane Gi/Go protein signal transducer pathway.
大黄素是大黄中的一种天然蒽醌。在传统中药中，它已被确认为一种促进胃肠动力的药物。大黄素通过增加细胞内Ca(2+)浓度来收缩平滑肌。在许多平滑肌中，细胞内Ca(2+)浓度增加会激活Ca(2+)激活的Cl(-)通道（ClCA）。本研究旨在探讨大黄素对结肠平滑肌中ClCA通道的影响。采用四通道生理信号采集系统测量平滑肌条的等长收缩。用穿孔全细胞模式的EPC10记录ClCA电流。大黄素使结肠平滑肌条和细胞收缩，并增强ClCA电流。尼氟灭酸（NFA）和4',4'-二异硫氰基芪-2,2-二磺酸（DIDS）可阻断这些作用。Gi/Go蛋白抑制蛋白激酶A（PKA）和蛋白激酶C（PKC），而PKA和PKC会降低ClCA电流。百日咳毒素（PTX，Gi/Go蛋白的特异性抑制剂）、8-溴腺苷3',5'-环一磷酸（8-BrcAMP，一种可透过细胞膜的蛋白激酶A激活剂）和佛波醇-12-肉豆蔻酸酯-13-乙酸酯（PMA，一种可透过细胞膜的蛋白激酶C激活剂）显著抑制了对ClCA电流的影响。我们的研究结果表明，大黄素通过增强ClCA通道来收缩结肠平滑肌，且这种作用主要是由膜Gi/Go蛋白信号转导途径的增强所诱导的。
