title: Responses of intraocular pressure and the pupil of feline eyes to prostaglandin EP1 and FP receptor agonists.
abstract: OBJECTIVE
  Previous studies suggested that FP receptors do not mediate the relaxation of the ciliary muscle and reduction of intraocular pressure in cats by prostaglandin (PG) F2alpha. The present study was undertaken to determine whether the reduction of intraocular pressure in cats induced by PGF2alpha is mediated by FP or other prostaglandin receptors.
  
  
  METHODS
  One eye of each cat was treated topically with prostaglandin F2alpha, fluprostenol (FP receptor agonist), or 17-phenyl trinor PGE2 (EP1 receptor agonist) in a dose range of 12.5 to 50 microg. The effects of SC19220 and SC51089 (EP1 receptor antagonists), BWA868c, and SQ29548 (DP and TP receptor antagonists, respectively) on the intraocular response to PGF2alpha were also examined. At intervals up to 6 hours after treatment, intraocular pressure was measured with a pneumotonometer, and pupil diameters were measured with a millimeter ruler.
  
  
  RESULTS
  In the dose ranges used, PGF2alpha and 17-phenyl trinor PGE2 decreased intraocular pressure and pupil diameter. The greatest reduction of intraocular pressure by 50.0 microg PGF2alpha was 5.0+/-1.4 mm Hg, whereas that by 50 microg 17-phenyl trinor PGE2 was 6.2+/-1.5 mm Hg. The isopropyl ester of PGF 2alpha at a dose of 1.25 microg reduced intraocular pressure by 3.75+/-0.25 mm Hg at 2 hours. At doses up to 100 microg, fluprostenol did not decrease intraocular pressure but did reduce pupil diameter. SC19220, a weak but selective EP1 receptor antagonist, inhibited the intraocular pressure response to both PGF2alpha and 17-phenyl trinor PGE2. The more potent EP1 receptor antagonist SC51089 had a greater inhibitory effect than SC19220 on the intraocular pressure response to PGF2alpha. Both of these antagonists had a small but non-dose dependent and statistically insignificant effect on the pupil response to PGF2alpha. These observations suggest that in cats, intraocular pressure and pupil responses to PGF2alpha, are mediated by EP1 and FP receptors, respectively. However, SC19220 significantly and dose-dependently inhibited the pupil response to 17-phenyl trinor PGE2alpha suggesting that EP1 receptors mediate pupil response to this agonist. DP and TP receptor antagonists at doses 5- to 20-fold greater than the IC50 values had no effect on the ocular hypotensive response to PGF2alpha. The concurrent administration of 12.5 microg of each of PGF2alpha and 17-phenyl trinor PGE2 did not produce an additive effect on intraocular pressure, indicating that in cats PGF2alpha and 17-phenyl trinor PGE2 act on the same receptor type.
  
  
  CONCLUSIONS
  These results suggest that a significant proportion of the ocular hypotensive action of PGF2alpha in cats is mediated by EP1 but not by FP receptor. Evidence was also provided to show that 17-phenyl trinor PGE2 is an ocular hypotensive agent in cats.
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Louisville, Kentucky 40202, USA. p0bhat01@ulkyvm.louisville.edu
authors.forename: P
authors.initials: P
authors.lastname: Bhattacherjee
authors.forename: B S
authors.initials: BS
authors.lastname: Williams
authors.forename: C A
authors.initials: CA
authors.lastname: Paterson
mesh_terms: D000818:Animals; D002415:Cats; D015237:Dinoprost / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007429:Intraocular Pressure / Q000187:drug effects*; D000077338:Latanoprost; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology*; D011680:Pupil / Q000187:drug effects*; D011897:Random Allocation; D011982:Receptors, Prostaglandin / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000502:physiology; D018078:Receptors, Prostaglandin E / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000502:physiology; D058306:Receptors, Prostaglandin E, EP1 Subtype; D014065:Tonometry, Ocular
chemical_list: D011448:Prostaglandin Antagonists; D011461:Prostaglandins F, Synthetic; D011982:Receptors, Prostaglandin; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; C034671:prostaglandin F2alpha receptor; C006326:fluprostenol; D000077338:Latanoprost; D015237:Dinoprost