期刊
PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS
卷 88, 期 4, 页码 321-330出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.plefa.2013.01.007
关键词
Smooth muscle relaxation; Prostanoid EP2 receptor; Prostanoid TP receptor; ONO-AE1-259; Butaprost; CP-533536; EP2 Receptor antagonist; Onset/offset kinetics; Lipophilicity; Limited diffusion model
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). (c) 2013 Elsevier Ltd. All rights reserved.
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