title: Hydroxycinnamic acid amides from Scopolia tangutica inhibit the activity of M1 muscarinic acetylcholine receptor in vitro.
abstract: Scopolia tangutica Maxim (S. tangutica) extracts have been traditionally used as antispasmodic, sedative, and analgesic agents in Tibet and in the Qinghai province of China. Their active compositions are however poorly understood. We have recently isolated five new hydroxycinnamic acid (HCA) amides along with two known HCA amides, one cinnamic acid amide from these extracts. In this study, we evaluate their abilities to inhibit carbacol-induced activity of M1 muscarinic acetylcholine receptor along with the crude extracts. Chinese hamster ovary cells stably expressing the recombinant human M1 receptor (CHO-M1 cells) were employed to evaluate the anticholinergic potentials. Intracellular Ca(2+) changes were monitored using the FLIPR system. Five HCA amides as well as the crude S. tangutica extract displayed dose-dependent inhibitory effects against M1 receptor. These findings demonstrate that HCA amides are part of the M1 receptor-inhibiting principles of S. tangutica. Since blockade of parasympathetic nerve impulse transmission through the inhibition of the M1 receptor lessens smooth muscle spasms, our findings provided a molecular explanation for the traditional use of S. tangutica against spasm.
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China. Electronic address: zhangyan_sjtu@sjtu.edu.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key laboratory of Separation Science for Analytical Chemistry, Key Lab of Natural Medicine, Liaoning Province, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, People's Republic of China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Long
authors.affiliation: Key laboratory of Separation Science for Analytical Chemistry, Key Lab of Natural Medicine, Liaoning Province, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, People's Republic of China.
authors.forename: Zhimou
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Department of Pharmacology, University of California, Irvine, CA 92697, United States.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Key laboratory of Separation Science for Analytical Chemistry, Key Lab of Natural Medicine, Liaoning Province, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, People's Republic of China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Ye
authors.affiliation: Key laboratory of Separation Science for Analytical Chemistry, Key Lab of Natural Medicine, Liaoning Province, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, People's Republic of China.
authors.forename: Xinmiao
authors.initials: X
authors.lastname: Liang
authors.affiliation: Department of Pharmacology, University of California, Irvine, CA 92697, United States.
authors.forename: Olivier
authors.initials: O
authors.lastname: Civelli
mesh_terms: D000818:Animals; D016466:CHO Cells; D003373:Coumaric Acids / Q000494:pharmacology*; D003412:Cricetulus; D004365:Drugs, Chinese Herbal / Q000737:chemistry; D006801:Humans; D015394:Molecular Structure; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D010936:Plant Extracts / Q000737:chemistry*; D018517:Plant Roots / Q000737:chemistry; D043643:Receptor, Muscarinic M1 / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins; D032603:Scopolia / Q000737:chemistry*
chemical_list: D003373:Coumaric Acids; D004365:Drugs, Chinese Herbal; D018727:Muscarinic Antagonists; D010936:Plant Extracts; D043643:Receptor, Muscarinic M1; D011994:Recombinant Proteins
keywords: Hydroxycinnamic acid amides; M1 muscarinic acetylcholine receptor; Scopolia tangutica Maxim