Induction of cytochrome P-450 isozyme 3a (P-450IIE1) in rabbit olfactory mucosa by ethanol and acetone

X. Ding, M. J. Coon

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Cytochrome P-450 isozyme 3a, the alcohol-inducible form of cytochrome P-450 (P-450IIE1), was previously identified in rabbit nasal microsomes with the use of immunochemical techniques; the occurrence of this cytochrome in the nasal mucosa was subsequently confirmed through RNA hybridization experiments. However, in contrast to the well established inducibility of isozyme 3a in liver and kidney by alcohol treatment of the animals, no induction was observed in the nasal tissue with the use of a polyclonal anti-3a antibody for immunochemical quantitation. Recently, two new P-450 isozymes, designated NMa and NMb, were identified in rabbit nasal microsomes, and were found to have overlapping substrate specificity with isozyme 3a. Moreover, the two new cytochromes cross-react with the polyclonal anti-3a antibody that was used in the earlier study for quantitation of nasal isozyme 3a. These recent findings invalidate our previous conclusion that isozyme 3a is not induced by ethanol treatment of rabbits. In the present study, immunoblot quantitation of isozyme 3a was performed with a monoclonal anti-3a antibody that does not recognize either NMa or NMb, and the nasal microsomal metabolism of butanol was examined at various substrate concentrations. We have found that the level of isozyme 3a protein in nasal mucosa is elevated about 2-fold after treatment of the animals with ethanol and about 6-fold after treatment with acetone. Furthermore, corresponding increases in the rate of microsomal butanol oxidation were observed at low substrate concentrations. Thus, we conclude that P-450 isozyme 3a is, in fact, inducible in the nasal tissues by ethanol or acetone treatment of rabbits.

Original languageEnglish (US)
Pages (from-to)742-745
Number of pages4
JournalDrug Metabolism and Disposition
Volume18
Issue number5
Publication statusPublished - Nov 1 1990
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Cite this