细胞色素P4502A5的表达及苯巴比妥对其的诱导作用受环磷酸腺苷（cAMP）在小鼠原代肝细胞中的调控。

Cytochrome P4502A5 expression and inducibility by phenobarbital is modulated by cAMP in mouse primary hepatocytes.

作者信息

Salonpää P, Pelkonen O, Kojo A, Pasanen M, Negishi M, Raunio H

机构信息

Department of Pharmacology and Toxicology, University of Oulu, Finland.

出版信息

Biochem Biophys Res Commun. 1994 Nov 30;205(1):631-7. doi: 10.1006/bbrc.1994.2712.

DOI:10.1006/bbrc.1994.2712

PMID:7528014

Abstract

Factors involved in CYP2A5 expression were studied in mouse liver primary hepatocytes in culture. CYP2A5-mediated coumarin 7-hydroxylase (COH) activity was retained in simple culture conditions for at least 96 hours and the activity was inducible up to 33-fold by phenobarbital (PB). The constitutive activity and inducibility of COH was totally blocked by treatment of hepatocytes with actinomycin D, and short initial treatment with cycloheximide caused superinducibility when co-administered with PB. Treatment of hepatocytes with inhibitors of protein kinase C, tyrosine kinases and a generator of nitric oxide did not affect COH basal activity or inducibility. Administration of dibutyryl cAMP, forskolin, and 3-isobutyl-1-methylxanthine (IBMX) enhanced both basal and PB-induced COH activities and CYP2A5 mRNA levels, indicating that cAMP plays a major role in CYP2A5 expression.

摘要

在培养的小鼠肝脏原代肝细胞中研究了参与CYP2A5表达的因素。CYP2A5介导的香豆素7-羟化酶（COH）活性在简单培养条件下至少保留96小时，并且该活性可被苯巴比妥（PB）诱导高达33倍。用放线菌素D处理肝细胞可完全阻断COH的组成型活性和诱导性，当与PB共同给药时，用环己酰亚胺进行短暂的初始处理会导致超诱导。用蛋白激酶C抑制剂、酪氨酸激酶抑制剂和一氧化氮生成剂处理肝细胞不会影响COH的基础活性或诱导性。给予二丁酰cAMP、福斯可林和3-异丁基-1-甲基黄嘌呤（IBMX）可增强基础和PB诱导的COH活性以及CYP2A5 mRNA水平，表明cAMP在CYP2A5表达中起主要作用。