COVALENT MODIFICATION OF RAT-LIVER DIPEPTIDYL PEPTIDASE-IV (CD26) BY THE NONSTEROIDAL ANTIINFLAMMATORY DRUG DICLOFENAC

被引：79

作者：

HARGUS, SJ

MARTIN, BM

GEORGE, JW

POHL, LR

机构：

[1] GEORGETOWN UNIV, DEPT ANESTHESIA, WASHINGTON, DC USA

[2] NIMH, CLIN NEUROSCI BRANCH, BETHESDA, MD 20892 USA

来源：

CHEMICAL RESEARCH IN TOXICOLOGY | 1995年 / 8卷 / 08期

关键词：

D O I：

10.1021/tx00050a001

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Diclofenac is a nonsteroidal anti-inflammatory drug that has been implicated in several cases of severe hepatotoxicity. Our previous study showed that diclofenac metabolites bound covalently and selectively to rat liver plasma membrane proteins with estimated monomeric masses of 110, 140, and 200 kDa. We report here that we have identified the 110 kDa diclofenac-labeled protein in rat liver as dipeptidyl peptidase IV, also known as CD26. In addition, we found that the activity of dipeptidyl peptidase IV in liver plasma membrane fractions was lowered after diclofenac treatment of rats. These results suggest that the hepatotoxicity associated with diclofenac might be due, in part, to the covalent modification of dipeptidyl peptidase IV.

引用

页码：993 / 996

页数：4

共 33 条

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