Raufman Jean-Pierre, Cheng Kunrong, Zimniak Piotr
VA Maryland Health Care System and Department of Medicine, Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, Maryland 21201-1595, USA.
Dig Dis Sci. 2003 Aug;48(8):1431-44. doi: 10.1023/a:1024733500950.
Besides their known physiological actions, bile acids are signaling molecules that alter cell function by interacting with muscarinic and nuclear receptors. Bile acid interaction with nuclear receptors modulates bile acid and cholesterol metabolism, whereas the potential consequences of muscarinic receptor activation are much broader. This review examines recent discoveries regarding bile acid interaction with muscarinic receptors. Selective and functional bile acid interaction has been reported with M3 receptors expressed in guinea pig gastric chief cells, human colon cancer cells, and transfected Chinese hamster ovary cells. Interaction of bile acids with chief cells may contribute to mucosal damage and other pathophysiological consequences of bile reflux. Bile acid-induced stimulation of muscarinic receptors on colon cancer cells may contribute to cellular proliferation and neoplasia. Potential consequences of bile acid interaction with muscarinic receptors on gastrointestinal myocytes, biliary epithelium, vascular endothelium and dermal neurons are discussed. Elucidation of molecular mechanisms underlying interaction of bile acids with muscarinic receptors may suggest new treatments for conditions that result from such interactions.
除了其已知的生理作用外，胆汁酸还是通过与毒蕈碱受体和核受体相互作用来改变细胞功能的信号分子。胆汁酸与核受体的相互作用调节胆汁酸和胆固醇代谢，而毒蕈碱受体激活的潜在后果则更为广泛。本文综述了关于胆汁酸与毒蕈碱受体相互作用的最新发现。据报道，在豚鼠胃主细胞、人结肠癌细胞和转染的中国仓鼠卵巢细胞中表达的M3受体存在选择性和功能性胆汁酸相互作用。胆汁酸与主细胞的相互作用可能导致胆汁反流的黏膜损伤和其他病理生理后果。胆汁酸诱导的结肠癌细胞毒蕈碱受体刺激可能促进细胞增殖和肿瘤形成。本文还讨论了胆汁酸与毒蕈碱受体相互作用对胃肠道肌细胞、胆管上皮、血管内皮和皮肤神经元的潜在影响。阐明胆汁酸与毒蕈碱受体相互作用的分子机制可能为由此类相互作用导致的疾病提供新的治疗方法。
