Two different 7-ethoxycoumarin O-deethylase activities in mice after pretreatment with sulmazole and cobaltous chloride

Arzneimittelforschung. 1986 Dec;36(12):1756-60.

Abstract

Pretreatment of male C57BL/6J Han mice with 200 mg of sulmazole (AR-L 115 BS) daily for 2 days results in an up to 4fold increase of the 7-ethoxycoumarin O-deethylase. The resulting effect was compared to that after a pretreatment with cobaltous chloride which also leads to a 4fold increase. Enzyme kinetic parameters of the 7-ethoxycoumarin O-deethylase are different for the two inducers in respect to the affinity for the substrate, but the inhibitions by metyrapone and alpha-naphthoflavone are similar. Comparison of the microsomal protein patterns after partial purification of microsomes revealed totally different patterns after sulmazole and cobaltous chloride. Sulmazole produces a 54 kDa protein band and cobaltous chloride a band at 48.5 kDa. Therefore it is concluded that in mice at least two 7-ethoxycoumarin O-deethylase activities can be induced. The electrophoretic pattern after sulmazole is different from those after 3-methylcholanthrene and isosafrole. This was also proven by enzyme kinetic investigations with ethoxyresorufin as substrate.

MeSH terms

  • 7-Alkoxycoumarin O-Dealkylase
  • Animals
  • Cobalt / pharmacology*
  • Dealkylation
  • Electrophoresis, Polyacrylamide Gel
  • Imidazoles / pharmacology*
  • In Vitro Techniques
  • Kinetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microsomes, Liver / enzymology
  • Oxygenases / metabolism*
  • Sodium Dodecyl Sulfate
  • Umbelliferones / metabolism

Substances

  • Imidazoles
  • Umbelliferones
  • Sodium Dodecyl Sulfate
  • Cobalt
  • Oxygenases
  • 7-Alkoxycoumarin O-Dealkylase
  • cobaltous chloride
  • sulmazole