EP3, but not EP2, FP, or TP prostanoid-receptor stimulation may reduce intraocular pressure.
Stimulation of DP, but not TP or FP, prostanoid receptors has previously been shown to reduce intraocular pressure (IOP) in rabbits. However the role of EP receptors (EP1, EP2, and EP3 subtypes) has not been studied extensively. Sulprostone, RS-61565, and RS-20216 have been studied for effects on rabbit IOP, and their prostanoid-receptor profiles characterized. The data suggest that the EP3, but not EP2, FP, or TP activity of these agonists correlated with the intraocular hypotensive effects. Moreover, RS-20216 lowered IOP at a dose of 5 micrograms for up to 12 hr after administration. In contrast to PGE1 and PGE2, which elicited both hyper- and hypotensive responses, sulprostone, RS-61565, and RS-20216 elicited only a hypotensive responses with no signs of ocular irritation. Thus stimulation of the EP3 receptor results in a lowering of IOP in rabbits. Compounds specific for this receptor subtype may act as novel therapeutic agents for the treatment of glaucoma.
Waterbury
L D
LD
Institute of Pharmacology, Syntex Research, Palo Alto, California, 94304.
Eglen
R M
RM
Faurot
G F
GF
Cooper
G F
GF
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000527:Alprostadil; D000704:Analysis of Variance; D000818:Animals; D015232:Dinoprostone / Q000031:analogs & derivatives; D005260:Female; D006168:Guinea Pigs; D007429:Intraocular Pressure / Q000502:physiology*; D008297:Male; D015394:Molecular Structure; D009119:Muscle Contraction / Q000187:drug effects; D011450:Prostaglandin Endoperoxides, Synthetic; D011459:Prostaglandins E, Synthetic; D011465:Prostaglandins, Synthetic; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D011982:Receptors, Prostaglandin / Q000502:physiology*; D018078:Receptors, Prostaglandin E; D017482:Receptors, Thromboxane; D014065:Tonometry, Ocular
D011450:Prostaglandin Endoperoxides, Synthetic; D011459:Prostaglandins E, Synthetic; D011465:Prostaglandins, Synthetic; D011982:Receptors, Prostaglandin; D018078:Receptors, Prostaglandin E; D017482:Receptors, Thromboxane; C034671:prostaglandin F2alpha receptor; C066748:RS 20216; C066749:RS 61565; C016767:sulprostone; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000527:Alprostadil; D015232:Dinoprostone