Summary
The direct fluorometric assay of 7-ethoxycoumarin O-dealkylation allowed the detection of monooxygenase activity in homogenates of the jejunum part of the small intestine from mice. The activity was located in the microsomal fraction and could be increased up to tenfold after oral administration of phenobarbital. The induction also increased the level of NADPH-dichlorophenolindophenol reductase activity and cytochrome P 450. The inhibition of the O-dealkylating activity by carbon monoxide and its reversibility by light indicate the similarity to the liver monooxygenase system.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bohn, W., Ullrich, V., Staudinger, Hj.: Species of cytochrome P 450 in rat liver microsomes with different stereoselectivity for the binding and monooxygenation of (+)- and (−)-methylphenobarbital. Naunyn-Schmiedebergs Arch. Pharmak. 270, 41–55 (1971).
Conney, A. H.: Pharmacological implications of microsomal enzyme induction. Pharmacol. Rev. 19, 317–366 (1967).
Degkwitz, E., Ullrich, V., Staudinger, Hj., Rummel, W.: Metabolism and cytochrome P 450 binding spectra of (+)- and (−)-hexobarbital in rat liver microsomes. Hoppe-Seylers Z. physiol. Chem. 350, 547–553 (1969).
Gelboin, H. V., Blackburn, N. R.: The stimulatary effect of 3-methylcholanthrene on benzpyrene hydroxylase activity in several rat tissues. Cancer Res. 24, 356–360 (1964).
Gielen, J. E., Goujon, F. M., Nebert, D. W.: Genetic regulation of aryl-hydrocarbon hydroxylase. induction. J. biol. Chem. 247, 1127–1137 (1972).
Greim, H., Schenkman, J. B., Klotzbücher, M., Remmer, H.: The influence of phenobarbital on the turnover of hepatic microsomal cytochrome b5 and cytochrome P 450 hemes in the rat. Biochim. biophys. Acta (Amst.) 201, 20–25 (1970).
Hänninen, O., Aitio, H., Vainio, H.: Enhancement of drug oxidation and conjugation by carcinogenes in different rat tissue. 8th Meeting FEBS, Amsterdam 1972, Abstr., p. 870.
Hayaishi, O.: Proceedings of the plenary sessions. 6th Intern. Congr. of Biochem. Vol. 33, p. 31. New York City 1964, I.U.B.
Orrenius, S., Berg, A., Ernster, L.: Effects of trypsin on the electron transport systems of liver microsomes. Europ. J. Biochem. 11, 193–200 (1969).
Uehleke, H.: N-Hydroxylierung von p-Phenetidin in vivo und durch isolierte Mikrosomen aus Leber und Nieren: Stimulierung durch Phenobarbital-Vorbehandlung. Naunyn-Schmiedebergs Arch. Pharmak. exp. Path. 262, 434 (1969).
Uehleke, H., Greim, H.: Stimulierung der Oxidation von Fremdstoffen in Nierenmikrosomen durch Phenobarbital. Naunyn-Schmiedebergs Arch. Pharmak. exp. Path. 262, 152 (1968).
Ullrich, V.: Enzymatische Hydroxylierung mit molekularem Sauerstoff. Angew. Chem. 84, 689–724 (1972).
Ullrich, V., Weber, P.: The O-dealkylation of 7-ethoxycoumarin by liver microsomes. A direct fluorometric test. Hoppe-Seylers Z. physiol. Chem. 353, 1171–1177 (1972).
Wattenberg, L. W., Leong, J. L.: Induction of increased benzpyrene detoxification in the lung. Fed. Proc. 24, 494 (1965).
Wattenberg, L. W., Leong, J. L., Strand, P. J.: Benzpyrene hydroxylase activity in the gastrointestinal tract. Cancer Res. 22, 1120–1125 (1962).
Author information
Authors and Affiliations
Additional information
Supported by a grant of the Sonderforschungsbereich 38 “Membranes” of the University of the Saarland.
Rights and permissions
About this article
Cite this article
Lehrmann, C., Ullrich, V. & Rummel, W. Phenobarbital inducible drug monooxygenase activity in the small intestine of mice. Naunyn-Schmiedeberg's Arch. Pharmacol. 276, 89–98 (1973). https://doi.org/10.1007/BF00500781
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00500781