Lack of prostaglandin F2 alpha metabolism by human ocular tissues.
The ability of human and rabbit ocular tissues to degrade prostaglandins (PGs) was compared by following the metabolic fate of PGF2 alpha. No metabolism was observed in vitro after 5.0 hr incubation with human cornea, iris/ciliary body, or sclera, as indicated by the absence of a decrease in [3H]-PGF2 alpha concentration or the appearance of [3H]-PGF2 alpha metabolites with time. Similarly, no metabolism of PGF2 alpha was observed in vitro after 5.0 hr incubation with these various rabbit ocular tissues or iris/ciliary body homogenate, or in vivo after topical application to rabbit eyes. The only detectable radioactive peak corresponded to PGF2 alpha. Therefore, it is concluded that both human and rabbit ocular tissues lack the enzymes that typically deactivate prostaglandins by 15-OH dehydrogenation, omega-oxidation, and beta-oxidation. In contrast to ocular metabolism, PGF2 alpha was metabolized in the presence of rabbit lung homogenate: [3H]-PGF2 alpha decreased with the simultaneous formation of a metabolite in a time-dependent manner. This metabolic transformation in lung homogenate was NADP+ dependent, and the radioactive metabolic peak had the same retention time as 13,14-dihydro-15-keto-PGF2 alpha.
Cheng-Bennett
A
A
Department of Drug Metabolism, Allergan, Inc., Irvine, California 92715.
Poyer
J
J
Weinkam
R J
RJ
Woodward
D F
DF
D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D002924:Ciliary Body / Q000378:metabolism; D003228:Conjunctiva / Q000378:metabolism; D003315:Cornea / Q000378:metabolism; D015237:Dinoprost / Q000378:metabolism*; D005123:Eye / Q000378:metabolism*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007498:Iris / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D011817:Rabbits; D012590:Sclera / Q000378:metabolism
D015237:Dinoprost