Induction of Hepatic Microsomal UDP-Glucuronosyltransferase Activity in Nifedipine Treated Rats

UDP-Glucuronosyltransferase(UDPGT) activity was studies in hepatic microsomal preparation from rats treated with nifedipine. The substrates 1-naphthol, P-nitrophenol, 4-methyl-umbelliferone and bilirubine were used. With 1-naphthol, nifedipine 2 and 4 weeks treatment caused 6- and 7.3-fold, respectively, increase in activity over the control value. With 4-methylumbelliferone, nifedipine 2 and 4 weeks treatment caused 5- and 6-fold increase in activity over the control value. With P-nitrophenol, nifedipine 2 and 4weeks treatment caused both approximately 3-fold increase in activity over the control value. However bilirubin-UDPGT activity was not affected by this inducer effects of nifedipine on the hepatic monooxygenase system in rats were investigate. P-Nitroanisole-O-demethylase, NADPH-cytochrome C reductase activity and cytochrome P-450 content in nifedipine treated rats were significantly increased to 390, 290 and 150% of control rats, respectively.

The selectivity of nifedipine of UDP-glucuronosyltransferase was investigated in rat liver microsomes and compared with their effect on monooxygenase reactions. Similart o 3-meth-lycholanthrene-type selectively stimulated the glucuronidation induced both UDPGT₁ and monooxygenase activity, probably through a common receptor protein.