通过使用氟伏沙明和异黄樟素进行选择性抑制来区分CYP1A1和CYP1A2的活性。

Distinction of CYP1A1 and CYP1A2 activity by selective inhibition using fluvoxamine and isosafrole.

作者信息

Pastrakuljic A, Tang B K, Roberts E A, Kalow W

机构信息

Department of Pharmacology, University of Toronto, Ontario, Canada.

出版信息

Biochem Pharmacol. 1997 Feb 21;53(4):531-8. doi: 10.1016/s0006-2952(96)00769-1.

DOI:10.1016/s0006-2952(96)00769-1

PMID:9105404

Abstract

Ethoxyresorufin O-deethylation (EROD) has been used as a specific probe for CYP1A1 and CYP1A2. Selective inhibition of one of these cytochromes P450 may differentiate their activity in human liver. Four inhibitors were chosen to examine the selective inhibition of EROD activity, using cDNA of CYP1A1 and CYP1A2. The two flavones, alpha-naphthoflavone and apigenin, while differing in potency, inhibited expressed human CYP1A1, CYP1A2, and human liver microsomes to a similar extent. Isosafrole and fluvoxamine were found to inhibit CYP1A2 selectively, with Ki values of 14 and 800 times, respectively, lower than those for CY1A1. A set of equations was developed to estimate both CYP1A1 and CYP1A2 activity. Levels of CYP1A2 in four human liver specimens ranged from 44.4 to 76.7 pmol/mg protein, which significantly correlated with phenacetin O-deethylase activity (r = 0.99; P < 0.001). Low levels of CYP1A1 activity were present in all four investigated livers, ranging from 0.4 to 2.7 pmol/mg protein.

摘要

乙氧异吩恶唑酮-O-脱乙基酶（EROD）已被用作CYP1A1和CYP1A2的特异性探针。对这些细胞色素P450之一的选择性抑制可能会区分它们在人肝脏中的活性。选择了四种抑制剂，使用CYP1A1和CYP1A2的cDNA来检测对EROD活性的选择性抑制。两种黄酮类化合物，α-萘黄酮和芹菜素，虽然效力不同，但对表达的人CYP1A1、CYP1A2和人肝微粒体的抑制程度相似。发现异黄樟素和氟伏沙明对CYP1A2有选择性抑制作用，其Ki值分别比CY1A1低14倍和800倍。开发了一组方程式来估计CYP1A1和CYP1A2的活性。四个人肝标本中CYP1A2的水平在44.4至76.7 pmol/mg蛋白质之间，这与非那西丁O-脱乙基酶活性显著相关（r = 0.99；P < 0.001）。在所有四个研究的肝脏中都存在低水平的CYP1A1活性，范围为0.4至2.7 pmol/mg蛋白质。