Interactions of prostaglandins with hepatic microsomal cytochrome P-450

Abstract

The spectral changes associated with the addition of prostaglandins (PGs) to hepatic microsomes from guinea pigs and rats were examined. PGAI, PGA2, PGE 1, PGE 2, PGF 1α and PGF 2α when added to guinea pig liver microsomes exhibited type I spectra. The binding affinities as determined from spectral dissociation constants (K s) were highest with PGA 1 and PGA 2. With liver microsomes from control or 3-methylcholanthrene (MC)-treated rats, PGs did not yield type I spectra; however, in this case a weak spectrum, designated here as type “II” was at times observed. With microsomes from phenobarbital (Pb)-treated rats only PGA 1 and PGA 2 yielded type I spectra; again in absence of type I spectrum, a weak type “II” was occasionally observed. The addition of PGA 1 and PGA 2 to liver microsomes from Pb-treated rats inhibited the microsomal mediated hydroxylation of hexobarbital. The inhibition by PGA 1 was competitive; the K i = 8.2 × 10 −4 M was found to be similar in magnitude to the K s = 7.3 × 10 −4 M of PGA 1 observed with rat liver microsomes. These observations suggested that PGs particularly of the A series interact with the hepatic microsomal cytochrome P-450 monooxygenase system.