title: Role of PGE2 in the colonic motility: PGE2 generates and enhances spontaneous contractions of longitudinal smooth muscle in the rat colon.
abstract: The aim of this study was to determine which PGE2 receptors (EP1-4 receptors) influence colonic motility. Mucosa-free longitudinal smooth muscle strips of the rat middle colon spontaneously induced frequent phasic contractions (giant contractions, GCs) in vitro, and the GCs were almost completely abolished by a cyclooxygenase inhibitor, piroxicam, and by an EP3 receptor antagonist, ONO-AE3-240, but enhanced by tetrodotoxin (TTX). In the presence of piroxicam, exogenous PGE2, both ONO-AE-248 (EP3 agonist), and ONO-DI-004 (EP1 agonist) induced GC-like contractions, and increased the frequency and amplitude. These effects of EP receptor agonists were insensitive to TTX and ω-conotoxins. In immunohistochemistry, the EP1 and EP3 receptors were expressed in the longitudinal smooth muscle cells. These results suggest that the endogenous PGE2 spontaneously generates and enhances the frequent phasic contractions directly activating the EP1 and EP3 receptors expressed on longitudinal smooth muscle cells in the rat middle colon.
authors.affiliation: Laboratory of Physiology, Graduate School of Integrated Pharmaceutical and Nutritional Sciences/Institute for Environmental Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Iizuka
authors.forename: Atsukazu
authors.initials: A
authors.lastname: Kuwahara
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Karaki
mesh_terms: D000527:Alprostadil / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005769:Gastrointestinal Motility / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D010894:Piroxicam / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D058306:Receptors, Prostaglandin E, EP1 Subtype / Q000819:agonists / Q000378:metabolism; D058308:Receptors, Prostaglandin E, EP3 Subtype / Q000819:agonists / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D016861:Cyclooxygenase Inhibitors; C121546:ONO AE 248; C500045:ONO-DI-004; C545637:Ptger1 protein, rat; C545649:Ptger3 protein, rat; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058308:Receptors, Prostaglandin E, EP3 Subtype; D010894:Piroxicam; D000527:Alprostadil; D015232:Dinoprostone