Hideyuki Nishiwaki (1,2), Noriko Saitoh (1), Hideaki Nishio (1), Tadayoshi
Takeuchi (1,3) and Fumiaki Hata (1,3,*)
(1) Department of Veterinary Pharmacology, College of Agriculture and (3) Department of Molecular Physiology and Biochemistry, Research Institute for Advanced Science and Technology, Osaka Prefecture University, Sakai 599-8531, Japan
(2) Kawanishi Pharma Research Institute, Nippon Boehringer Ingelheim Co., Ltd., Kawanishi 666-0131, Japan
(*) To whom correspondence should be addressed (1).
Abstract: Endomorphin-1 and -2, putative endogenous ligands for the mu-opioid receptor, inhibited acetylcholine (ACh) release evoked by electrical field stimulation (EFS) at 1 Hz, which partially activates muscarinic autoreceptors, but not at 10 Hz, which fully activates muscarinic autoreceptors, in longitudinal muscle with the myenteric plexus (LMMP) preparations of guinea pig ileum. After blockade of autoinhibition by atropine, the peptides also inhibited EFS-evoked ACh release at 10 Hz. The inhibitory effects on ACh release were abolished by the mu-opioid antagonist cyprodime. These results suggest that endomorphin-1 and -2 inhibit ACh release from LMMP preparations of guinea pig ileum and that the mechanism of the inhibition must have a component in common with muscarinic autoinhibition.
Keywords: Endomorphin, Acetylcholine release, Autoinhibition