title: Nature of the slow relaxation of smooth muscle induced by a EP2 receptor agonist with a non-prostanoid structure.
abstract: The remarkably slow onset/offset of relaxation of guinea-pig isolated trachea induced by a 'non-prostanoid' EP2 receptor agonist, (o-(o-benzyloxy)-cinnamyl)-cinnamic acid (coded (L)-9), was investigated. (L)-9 kinetics was slightly faster on mouse trachea and considerably faster on rabbit vena cava. In each case, reversal of (L)-9 relaxation by the selective EP2 antagonist ACA-23 was rapid and similar to other EP2 agonists (e.g. ONO-AE1-259). On guinea-pig aorta, in the presence of extensive EP2 receptor blockade, (L)-9 inhibited TP agonist-induced contraction more slowly than TP antagonists of similar affinity. The slower kinetics of (L)-9 appear to correlate with greater adventitial/submucosal barriers and thicker smooth muscle layers in the tissues examined. It is proposed that interactions of (L)-9 with EP2 and TP receptors are not rate-limiting, rather diffusion to and from the centre of the muscle mass is retarded by the high lipophilicity of (L)-9 (logP=6.69; ONO-AE1-259=3.95).
authors: Cardiovascular Research Group, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK. robert.l.jones@strath.ac.uk
authors: Robert L
authors: RL
authors: Jones
authors: Wan A N
authors: WA
authors: Wan Ahmad
authors: David F
authors: DF
authors: Woodward
authors: Jenny
authors: J
authors: Wang
mesh_terms: D000818:Animals; D015232:Dinoprostone / Q000031:analogs & derivatives* / Q000494:pharmacology; D006168:Guinea Pigs; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000819:agonists*; D014132:Trachea / Q000187:drug effects / Q000378:metabolism*
chemical_list: C499423:9-deoxy-9-chloro-15-deoxy-16-hydroxy-17,17-trimethylene-19,20-didehydroprostaglandin E2; D058307:Receptors, Prostaglandin E, EP2 Subtype; D015232:Dinoprostone