Nakamura M, Shirasawa E, Hikida M
Central Research Laboratories, Santen Pharmaceutical Co., Ltd., Osaka, Japan.
Ophthalmic Res. 1993;25(1):46-51. doi: 10.1159/000267220.
We characterized the interaction of the prodrug dipivefrin hydrochloride (DPE) with esterase activity in the rabbit cornea. The esterases which were identified included: (1) cholinesterase, (2) acetylcholinesterase, (3) a mixture containing carboxylesterase, acetylesterase and arylesterase, and (4) a non-specific esterase. DPE suppressed all of their activities as well as that of the mixture containing carboxylesterase, acetylesterase and arylesterase, and a nonspecific esterase. However, its effect on cholinesterase was larger than on any of the other activities, suggesting that DPE is a better substrate for cholinesterase than for any of the other esterases. These measurements along with those of substrate-dependent inhibition of 14C-DPE hydrolysis indicated that the DPE-esterase interaction was competitive based on changes in the apparent Km values which were extracted from Lineweaver-Burk plots of esterase activity. The substrate for cholinesterase competed with DPE most strongly among substrates. These results seem to suggest that DPE is hydrolyzed by various corneal esterases, mainly cholinesterase.
我们对前药盐酸地匹福林（DPE）与兔角膜中酯酶活性的相互作用进行了表征。鉴定出的酯酶包括：（1）胆碱酯酶，（2）乙酰胆碱酯酶，（3）一种含有羧酸酯酶、乙酰酯酶和芳基酯酶的混合物，以及（4）一种非特异性酯酶。DPE抑制了它们所有的活性以及含有羧酸酯酶、乙酰酯酶和芳基酯酶的混合物和非特异性酯酶的活性。然而，它对胆碱酯酶的作用比对任何其他活性的作用都更大，这表明DPE作为胆碱酯酶的底物比作为任何其他酯酶的底物更好。这些测量结果以及对14C-DPE水解的底物依赖性抑制的测量结果表明，基于从酯酶活性的Lineweaver-Burk图中提取的表观Km值的变化，DPE与酯酶的相互作用是竞争性的。在底物中，胆碱酯酶的底物与DPE的竞争最为强烈。这些结果似乎表明DPE被多种角膜酯酶水解，主要是胆碱酯酶。
