Su T, He W, Gu J, Lipinskas T W, Ding X
Wadsworth Center, New York State Department of Health, Albany, NY 12201-0509, USA.
Drug Metab Dispos. 1998 Aug;26(8):822-4.
The effects of pyrazole, which is known to induce hepatic cytochrome P4502A5 (CYP2A5) through posttranscriptional mechanisms, on the level of CYP2A5 in liver and extrahepatic tissues were examined in this study. Intraperitoneal administration of pyrazole at 200 mg/kg for 3 days induced CYP2A4/5 mRNAs and proteins and microsomal coumarin 7-hydroxylation activity in liver and kidney of C57BL/6 mice. A marginal increase (30%) in CYP2A4/5 mRNAs was also observed in the olfactory mucosa but not in the lung, and no increase in CYP2A4/5 proteins or microsomal coumarin 7-hydroxylation activity was observed in either the olfactory mucosa or lung. CYP2A4/5 proteins were not detected on immunoblots in other tissues examined, including breast, bone marrow, testis, prostate, ovary, and uterus from control or pyrazole-treated mice. On the other hand, pyrazole treatment induced CYP2E1 in the olfactory mucosa as well as in liver and kidney, indicating that the olfactory mucosa was exposed to pyrazole. The lack of CYP2A inducibility in the olfactory mucosa was also observed for several other known inducers of hepatic CYP2A5, including cobaltous chloride, stannous chloride, griseofulvin, thioacetamide, and aminotriazole. These results suggest that the mechanisms involved in the induction of hepatic and renal CYP2A5 by pyrazole and other xenobiotic compounds may be tissue-specific.
已知吡唑可通过转录后机制诱导肝细胞色素P4502A5（CYP2A5），本研究检测了吡唑对肝脏和肝外组织中CYP2A5水平的影响。对C57BL/6小鼠腹腔注射200mg/kg吡唑，连续3天，可诱导肝脏和肾脏中CYP2A4/5 mRNA和蛋白以及微粒体香豆素7-羟化活性。在嗅觉黏膜中也观察到CYP2A4/5 mRNA有轻微增加（30%），但在肺中未观察到，且在嗅觉黏膜或肺中均未观察到CYP2A4/5蛋白或微粒体香豆素7-羟化活性增加。在检测的其他组织（包括来自对照或吡唑处理小鼠的乳腺、骨髓、睾丸、前列腺、卵巢和子宫）的免疫印迹中未检测到CYP2A4/5蛋白。另一方面，吡唑处理可诱导嗅觉黏膜以及肝脏和肾脏中的CYP2E1，表明嗅觉黏膜接触到了吡唑。对于其他几种已知的肝脏CYP2A5诱导剂，包括氯化钴、氯化亚锡、灰黄霉素、硫代乙酰胺和氨基三唑，在嗅觉黏膜中也观察到缺乏CYP2A诱导性。这些结果表明，吡唑和其他外源性化合物诱导肝脏和肾脏CYP2A5的机制可能具有组织特异性。
