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
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.