title: In vitro characterization of the effects of endomorphin 1 and 2, endogenous ligands for mu-opioid receptors, on mouse colonic motility.
abstract: The effects of endomorphin 1 (EM1) and 2 (EM2) in colonic motility remain unknown. We investigated the effects and mechanisms of these endomorphins (EMs) on the colonic motility in vitro by applying various neural blocking agents and various opioid receptor antagonists. EMs (10(-9) to 10(-6)M) displayed significant stimulatory effects on the basal tonus or spontaneous activity of mouse colon but not of stomach and small intestine. It is noteworthy that the contractile actions of EMs varied slightly among different regions of colonic longitudinal muscle layers, whereas the contractile responses induced by EMs were significantly different among different regions of circular muscle layers. EMs-induced longitudinal or circular muscle contractions were not significantly affected by atropine, N(G)-nitro-l-arginine methyl ester, phentolamine, propranolol and methysergide. Tetrodotoxin, indomethacin and naloxone completely abolished the EMs-induced colonic contractions. Surprisingly, EMs (10(-7)M)-induced longitudinal muscle contractions were significantly attenuated by nor-binaltorphimine (3x10(-6)M). By contrast, pretreatment with naltrindole (10(-6)M) did not significantly affect EMs-induced longitudinal or circular muscle contractions. Interestingly, the circular muscle contractions in response to EM2 (10(-7)M) were not fully blocked by beta-funaltrexamine (6x10(-6)M). Naloxonazine (10(-6)M) almost fully antagonized the EMs-induced longitudinal or circular muscle contractions, and these effects could be only partially reversed by extensive washing. All the results indicated that the mechanisms and sites of actions of EMs were region-specific. Furthermore, these findings showed that the activation of multiple subtypes of opioid receptors, possibly including mu(1) (naloxonazine-sensitive), mu(2) and even other forms of muORs (beta-FNA-insensitive), was required for EMs-induced mouse colonic motility.
authors.affiliation: Institute of Biochemistry and Molecular Biology, State Key Laboratory of Applied Organic Chemistry, Lanzhou University, 222 Tian Shui South Road, Lanzhou 730000, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Yu
authors.forename: Yun
authors.initials: Y
authors.lastname: Cui
authors.forename: Xiang
authors.initials: X
authors.lastname: Wang
authors.forename: Lu-hao
authors.initials: LH
authors.lastname: Lai
authors.forename: Chang-Lin
authors.initials: CL
authors.lastname: Wang
authors.forename: Ying-zhe
authors.initials: YZ
authors.lastname: Fan
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D003106:Colon / Q000166:cytology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D005769:Gastrointestinal Motility / Q000187:drug effects*; D007421:Intestine, Small / Q000166:cytology; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology*; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000502:physiology*; D013270:Stomach / Q000166:cytology
chemical_list: D000701:Analgesics, Opioid; D009842:Oligopeptides; D017450:Receptors, Opioid, mu; C105293:endomorphin 1; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009020:Morphine