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.