Selective prostaglandin D2 receptor stimulation elicits ocular hypotensive effects in rabbits and cats.
The effects of the selective prostaglandin D2 (DP) receptor agonists, 572C85 ((+/-)-5-(3-carboxypropylthio)-1-(2-cyclohexyl-2-hydroxyethyl- amino)hexahydrocyclopenta(d)imidazol-2(1H)-one) and 192C86 ((+/-)-5-(3-carboxypropylthio)-1-(2-cyclohexyl-2-hydroxyethylidene - amino)-3-ethylhexahydrocyclopenta(d)imidazol-2(1H)-one), were determined on intraocular pressure regulation in rabbits and cats. 572C85 (50 micrograms) in rabbits maximally lowered intraocular pressure by 4.3 mm Hg, and significantly for 4 h compared to control. In cats 572C85 had a similar effect. 192C86 (50 micrograms) reduced intraocular pressure by 2.8 mm Hg for 2 h in rabbits. Following exposure to the specific DP receptor antagonist, BW A868C ((+/-)-3-benzyl-5-(6-carboxyhexyl)-1-(2-cyclohexyl-2-hydroxyethylamin o)- hydantoin; 50 micrograms), which had no effect on intraocular pressure by itself, 572C85 (50 micrograms) did not reduce intraocular pressure in rabbits and cats. The intraocular pressure lowering effect of the mixed DP and EP receptor agonist, BW245C (5-(6-carboxyhexyl)-1-(3-cyclohexyl-3-hydroxypropyl)-hydantoin; 50 micrograms), in cats was suppressed by only 64% by BW A868C (50 micrograms). These results clearly show that the DP receptors in rabbit and cat eyes are involved in intraocular pressure regulation. However, under baseline conditions DP receptor activity does not contribute to this regulation.
Matsugi
T
T
Developmental Research Laboratories, Santen Pharmaceutical Co., Ltd., Osaka, Japan.
Kageyama
M
M
Nishimura
K
K
Giles
H
H
Shirasawa
E
E
D000818:Animals; D002087:Butyrates / Q000494:pharmacology; D002415:Cats; D006827:Hydantoins / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007429:Intraocular Pressure / Q000187:drug effects*; D008297:Male; D011817:Rabbits; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin / Q000819:agonists / Q000502:physiology*
D002087:Butyrates; D006827:Hydantoins; D007093:Imidazoles; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; C058848:BW A868C; C078640:4-((1-((2-cyclohexyl-2-hydroxyethylidene)amino)-3-ethyloctahydro-2-oxo-5-cyclopentimidazolyl)thio)butanoic acid; C030669:BW 245C; C036293:prostaglandin D2 receptor