PROSTANOID-INDUCED RELAXATION OF PRECONTRACTED CAT CILIARY MUSCLE IS MEDIATED BY EP2 AND DP RECEPTORS

The pharmacology of prostanoid-induced relaxation of the precontracted cat ciliary smooth muscle was characterized using synthetic prostaglandin (PG) analogues that are selective for specific prostanoid receptors. Relaxation was studied using carbachol to precontract the isolated longitudinal ciliary muscle, followed by application of the PG agonist. Of the compounds studied, PGE2 was the most potent relaxant (concentration that produced 50% of maximum relaxation, 10(-7) mol/1), and its maximal effect in each preparation was used as a standard for comparison. Both PGD2 and PGF2alpha produced relaxations that were approximately 30- and 100-fold weaker, respectively, than those produced by PGE2. Prostanoids with activity at the EP2 (19-(R)-hydroxy PGE2 and 11-deoxy PGE1) and DP (BW 245C) receptors potently relaxed the ciliary muscle. Other EP receptor subtypes and the TP receptor were not involved as indicated by the lack of relaxant activity of sulprostone (EP3 > EP1), MB 28767 (EP3 > TP), and U46619 (TP). Although 17-phenyl trinor PGE, (EP, and EP3) and PGI2 (IP) had some activity, it occurred at a nonselective dose (10(-4) mol/l). The presence of DP receptors in the cat ciliary muscle was confirmed by using BW A868C, a selective DP-receptor antagonist. This drug (concentration, 1 mumol/l) displaced the relaxant effects of PGD2 but had no effect on the activities of PGE2 and 11-deoxy PGE1. In addition, 17-phenyl trinor PGF2alpha (FP) was inactive, indicating that the FP receptor was not involved in ciliary muscle relaxation. There was no evidence for prostanoid receptors that may mediate contraction of the ciliary muscle because the PGs studied had no contractile effects. These results indicate that PG-induced relaxation of the cat ciliary muscle precontracted by carbachol may be mediated by stimulation of both EP2 and DP receptors.