Induction of mouse CYP2J by pyrazole in the eye, kidney, liver, lung, olfactory mucosa, and small intestine, but not in the heart

Citation
Q. Xie et al., Induction of mouse CYP2J by pyrazole in the eye, kidney, liver, lung, olfactory mucosa, and small intestine, but not in the heart, DRUG META D, 28(11), 2000, pp. 1311-1316
Citations number
38
Categorie Soggetti
Pharmacology & Toxicology
Journal title
DRUG METABOLISM AND DISPOSITION
ISSN journal
00909556 → ACNP
Volume
28
Issue
11
Year of publication
2000
Pages
1311 - 1316
Database
ISI
SICI code
0090-9556(200011)28:11<1311:IOMCBP>2.0.ZU;2-T
Abstract
We have recently shown that rat CYP2J4 is inducible by pyrazole in liver, s mall intestine, and olfactory mucosa. The aim of the present study was to d etermine whether mouse CYP2Js are also inducible by pyrazole, which was kno wn to induce CYP2A5 in mouse liver and kidney, but not in lung or olfactory mucosa. CYP2J proteins were detected in mouse liver, lung, kidney, heart, eye, olfactory mucosa, and small intestine by immunoblot analysis with an a nti-CYP2J4 antibody. The microsomal level of the CYP2J4-related P450s in va rious mouse tissues ranked in the order of small intestine > olfactory muco sa > liver > kidney greater than or equal to heart > lung > eye. Induction of the CYP2J proteins was observed in the eye, liver, lung, kidney, olfacto ry mucosa, and small intestine, but not in the heart, after daily i.p. inje ction of pyrazole at 120 or 200 mg/kg for 3 days. CYP2J proteins were induc ed similarly in C57BL/6 and DBA/2 mice. CYP2A5 was detected in the small in testine in addition to liver and olfactory mucosa; however, treatment with pyrazole induced CYP2A5 in the liver, but not in the olfactory mucosa or th e small intestine. Induction of CYP2J mRNAs was also observed by RNA blot a nalysis with a CYP2J4 cDNA probe. RNA-polymerase chain reaction analysis sh owed that, in both untreated and pyrazole-treated mice, CYP2J5 was expresse d in the kidney and liver, but not in the other tissues examined, whereas C YP2J6 was detected in all tissues examined. The different tissue selectivit ies in CYP2A5 and CYP2J induction by pyrazole suggest involvement of differ ent regulatory mechanisms.