Interaction of drugs and steroids with human placental microsomes

Abstract

Human term placental microsomes contain relatively small amounts (approx. 0.1 nmoles) of cytochrome P-450 per milligram of protein as determined by carbon monoxide complexing. The other components of the mixed function oxidase (NADPH-cytochrome c-reductase and NADPH-cytochrome P-450 reductase) are present in amounts comparable to those in rat liver microsomes. No oxidative metabolism could be detected when p-nitroanisole, acetanilide, amphetamine and aniline were incubated with placental microsomes. Type II compounds such as aniline, p-aminophenol, nicotinamide and metyrapone induce binding spectra. No spectrum, however, could be recorded with dithionite reduced material to which metyrapone was added. Type I compounds (aminopyrine, hexobarbital, naphthalene and pentobarbital) produce no difference spectra. Steroid hormones show either type I or II or mixed type spectra. The spectral types in placental microsomes are in most cases the opposite ones from those in rat liver microsomes. Metyrapone is bound to placental microsomes and can be either displaced or modified by steroids. It is concluded that each type of microsomes exhibits different complexing properties.