Responses of intraocular pressure and the pupil of feline eyes to prostaglandin EP1 and FP receptor agonists

PURPOSE. Previous studies suggested that FP receptors do not mediate the re laxation of the ciliary muscle and reduction of intraocular pressure in cat s by prostaglandin (PG) F-2 alpha. The present study was undertaken to dete rmine whether the reduction of intraocular pressure in cats induced by PGF( 2 alpha) is mediated by FP or other prostaglandin receptors. METHODS. One eye of each cat was treated topically with prostaglandin F-2 a lpha, fluprostenol (FP receptor agonist), or 17-phenyl trinor PGE(2) (EP1 r eceptor agonist) in a dose range of 12.5 to 50 mu g. The effects of SC19220 and SC51089 (EP1 receptor antagonists), BWA868c, and SQ29548 (DP and TP re ceptor antagonists, respectively) on the intraocular response to PGF(2 alph a) were also examined. ht intervals up to 6 hours after treatment, intraocu lar pressure was measured with a pneumotonometer, and pupil diameters were measured with a millimeter ruler. RESULTS. In the dose ranges used, PGF(2 alpha) and 17-phenyl trinor PGE(2) decreased intraocular pressure and pupil diameter, The greatest reduction o f intraocular pressure by 50.0 mu g PGF(2 alpha) was 5.0 +/- 1.4 mm Hg, whe reas that by 50 mu g 17-phenyl trinor PGE(2) was 6.2 +/- 1.5 mm Hg. The iso propyl ester of PGF(2 alpha) at a dose of 1.25 mu g reduced intraocular pre ssure by 3.75 +/- 0.25 mm Hg at 2 hours. At doses up to 100 mu g, fluproste nol did not decrease intraocular pressure but did reduce pupil diameter. SC 19220, a weak but selective EP1 receptor antagonist, inhibited the intraocu lar pressure response to both PGF(2 alpha) and 17-phenyl trinor PGE(2). The more potent EP1 receptor antagonist SC51089 had a greater inhibitory effec t than SC19220 on the intraocular pressure response to PGF(2 alpha). Both o f these antagonists had a small but non-dose dependent and statistically in significant effect on the pupil response to PGF(2 alpha). These observation s suggest that in cats, intraocular pressure and pupil responses to PGF(2 a lpha) are mediated by EP1 and FP receptors, respectively. However, SC19220 significantly and dose-dependently inhibited the pupil response to 17-pheny l trinor PGE(2), suggesting that EP1 receptors mediate pupil response to th is agonist. DP and TP receptor antagonists at doses 5- to 20-fold greater t han the IC50 values had no effect on the ocular ypotensive response to PGF( 2 alpha). The concurrent administration of 12.5 mu g of each of PGF(2 alpha ) and 17-phenyl trinor PGE(2) did not produce an additive effect on intraoc ular pressure, indicating that in cats PGF(2 alpha) and 17-phenyl trinor PG E(2) act on the same receptor type. CONCLUSIONS. These results suggest that a significant proportion of the ocu lar hypotensive action of PGF(2 alpha) in cats is mediated by EP1 but not b y FP receptor. Evidence was also provided to show that 17-phenyl trinor PGE (2) is an ocular hypotensive agent in cats.