Cytochrome P-450(CYP) enzymes are important in catalyzing the hiotransffrmation on manyendogeneous compounds and xenobiotics, including drugs and carcinogens. In the presentstudy, effect of nifedipine a voltage dependent calcium channel blocker on the induction ofCYP1A1 and 2B1 was investigated. Change of CYP1A1 and 2B1 activities were measuredby using specific enzyme activities and Western blot analysis. CYP1A1, as quantified by ethoxyresorufin-0-deethylase activity and Western blot with monoclonal antibody 1-7-1, increasedin liver microsome of nifedipine-treated spontaneous hypertensive rat(SHR. 30mg/kg.b.w, twicea day for 3days) but not in kidney microsome. CYP2B1, as quantified by benzyloxyresorufin-O-dealkylase activity and Western blot wit]1 monoclonal antibody 2-66-3, markedly increasedin liver microsome of nifedipine-treated SHR but slightly in kidney microsome. The resultsdemonstrate that nifedipine is a potent inducer of CYP2B1 in SHR.

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.

The effects of Naloxone, narcotic antagonist, pretreated with normal saline, salicylate and hydrocortisone produced by with hypovolemic shock on the rates of cytochrome components, mixed function oxidation enzyme reactions and lipid peroxidation have been determined using hepatic microsomal fractions of rats. The treatments with either of the naloxone have increased the contents of cytochrome P-450 and b_5 and NADPH- or NADH-cytochrome C reductase. But pretreated with salicylate and hydrocortisone were not change as compared to the control. The rates of O-demethylation for p-nitroanisole were decreased. Naloxone decreased the formation of lipid peroxide by pretreated salicylate and hydrocortisone. These results indicate that naloxone showed effect not only increase of blood pressure and respiration, but also cytochrome components activity, mixed function oxidation enzyme reactions and lipid peroxidation in the hepatic microsomal fractions of rats.