Cheng-Bennett A, Poyer J, Weinkam R J, Woodward D F
Department of Drug Metabolism, Allergan, Inc., Irvine, California 92715.
Invest Ophthalmol Vis Sci. 1990 Jul;31(7):1389-93.
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.
通过追踪前列腺素F2α（PGF2α）的代谢命运，比较了人和兔眼组织降解前列腺素（PGs）的能力。用人角膜、虹膜/睫状体或巩膜孵育5.0小时后，体外未观察到代谢，这表现为[3H]-PGF2α浓度没有降低，也没有随着时间出现[3H]-PGF2α代谢物。同样，用这些不同的兔眼组织或虹膜/睫状体匀浆孵育5.0小时后，体外未观察到PGF2α的代谢，对兔眼进行局部应用后，体内也未观察到代谢。唯一可检测到的放射性峰对应于PGF2α。因此，可以得出结论，人和兔眼组织都缺乏通常通过15-羟基脱氢、ω-氧化和β-氧化使前列腺素失活的酶。与眼组织代谢不同，PGF2α在兔肺匀浆存在的情况下发生代谢：[3H]-PGF2α减少，同时以时间依赖性方式形成一种代谢物。肺匀浆中的这种代谢转化依赖于NADP+，放射性代谢峰的保留时间与13,14-二氢-15-酮-PGF2α相同。
