EFFECTS OF MORPHINE-SULFATE ON NADPH-CYTOCHROME-C REDUCTASE AND CYTOCHROME-P-450 OF MOUSE-LIVER MICROSOMES

Three h after i.p. administration of a single dose of 30 mg/kg of morphine to male mice, an increase in specific activity of NADPH-cytochrome c reductase by about 10% and the content of cytochrome P-450 by about 14% of their liver microsomes was observed. Administration of 30 mg/kg of morphine once daily during 5 days caused about 16% and 9% increases in specific activity of c reductase and the content of P-450, respectively. Administration of a single dose of morphine to male and female mice caused no sex-dependent differences in the specific activity of c reductase and the content of P-450. Repeated administration of morphine up to 100 mg/kg to male mice increased the specific activity of microsomal c reductase by about 70%. Repeated administration of morphine up to 55 mg/kg also increased the microsomal content of P-450 declined and finally dropped below control levels. The levels of c-reductase activity and P-450 content returned to normal levels about 2 wk after termination of morphine administration [The locus of morphine biotransformation may be at or near the locus of reductase and P-450 on the endoplasmic reticulum.].