Bruyère A, Declevès X, Bouzom F, Proust L, Martinet M, Walther B, Parmentier Y
Department of Pharmacokinetics and Drug Metabolism, Technologie Servier, Orleans, France.
Xenobiotica. 2009 Jan;39(1):22-32. doi: 10.1080/00498250802517714.
The objective of this study was to characterize cytochrome P450 (CYP) activities in both intestinal and hepatic microsomes from Wistar and Sprague-Dawley rats. Specific probes for measuring CYP activities were selected using rat recombinant CYP. The intestinal microsome preparation was optimized getting a more relevant and reproducible abundance of CYPs to measure CYP activities. Testosterone, propranolol, diclofenac, and midazolam were determined as specific substrates of rat CYP2C11, CYP2D2, CYP2C6, and CYP3A, respectively. Ethoxyresorufin and pentoxyresorufin were not specific substrates of CYP1A2 and CYP2B1, respectively. Hepatic and intestinal microsomes expressed active CYP1A1, CYP1A2, CYP2B1, and CYP3A2. Only liver expressed active CYP2C6, CYP2C11, and CYP2D2. Wistar liver expressed more active CYP1A and CYP3A2, but less active CYP2B1 than Wistar intestine. Sprague-Dawley liver expressed more active CYP2B1 and CYP3A2, but less active CYP1A than Sprague-Dawley intestine. In conclusion, CYP activities were qualitatively equivalent but not quantitatively in both strains.
本研究的目的是表征Wistar大鼠和Sprague-Dawley大鼠肠道和肝脏微粒体中的细胞色素P450（CYP）活性。使用大鼠重组CYP选择用于测量CYP活性的特异性探针。优化肠道微粒体制备，以获得更相关且可重复的CYP丰度来测量CYP活性。分别将睾酮、普萘洛尔、双氯芬酸和咪达唑仑确定为大鼠CYP2C11、CYP2D2、CYP2C6和CYP3A的特异性底物。乙氧异吩恶唑酮和戊氧异吩恶唑酮分别不是CYP1A2和CYP2B1的特异性底物。肝脏和肠道微粒体表达活性CYP1A1、CYP1A2、CYP2B1和CYP3A2。只有肝脏表达活性CYP2C6、CYP2C11和CYP2D2。Wistar大鼠肝脏中CYP1A和CYP3A2活性较高，但CYP2B1活性低于Wistar大鼠肠道。Sprague-Dawley大鼠肝脏中CYP2B1和CYP3A2活性较高，但CYP1A活性低于Sprague-Dawley大鼠肠道。总之，两种品系中CYP活性在质量上相当，但在数量上不同。
