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Identification of glucocorticoid-inducible cytochromes P-450 in the intestinal mucosa of rats and man.
Open accessAbstract
We used monoclonal antibodies and complementary DNAs (cDNAs) to glucocorticoid-inducible liver cytochromes P-450 in rats (P-450p) and in man (HLp) to search for related cytochromes in intestinal mucosa. In rat enterocytes, we found two dexamethasone-inducible proteins related to the steroid-inducible liver cytochromes P-450. Induction of these proteins in enterocytes was associated with increases in the amount of a P-450p-related messenger RNA and of erythromycin demethylase, an activity highly characteristic of P-450p and HLp. Similar studies on human jejunal enterocytes revealed a microsomal protein indistinguishable from HLp on immunoblots and an abundance of RNA hybridizing with HLp cDNA. In human enterocytes the specific concentration of the HLp-related cytochrome (measured immunochemically or as erythromycin demethylase activity) was similar to that found in human liver and could account for all of the CO-binding hemo-protein detected. We conclude that the intestinal mucosa contains prominent form(s) of cytochromes P-450 similar to liver cytochrome P-450p in their structure, function, and some regulatory characteristics.
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Cited by
THE HUMAN INTESTINAL CYTOCHROME P450 “PIE”
Paine, M. F., Hart, H. L., Ludington, S. S., Haining, R. L., Rettie, A. E., & Zeldin, D. C. (2006) · Drug Metabolism and Disposition · doi:10.1124/dmd.105.008672 · Cited by 870
Population-Based Mechanistic Prediction of Oral Drug Absorption
Jamei, M., Turner, D., Yang, J., Neuhoff, S., Polak, S., Rostami-Hodjegan, A., & Tucker, G. (2009) · The AAPS Journal · doi:10.1208/s12248-009-9099-y · Cited by 452
Sex-specific differences in CYP450 isoforms in humans
Scandlyn, M. J., Stuart, E. C., & Rosengren, R. J. (2008) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.4.4.413 · Cited by 199
Symposium Article: Molecular and Physical Mechanisms of First-Pass Extraction
Hall, S. D., Thummel, K. E., Watkins, P. B., Lown, K. S., Benet, L. Z., Paine, M. F., Mayo, R. R., Turgeon, D. K., Bailey, D. G., Fontana, R. J., et al. (1999) · Drug Metabolism and Disposition · doi:10.1016/s0090-9556(24)15271-3 · Cited by 109
Self-citationKomura, H., & Iwaki, M. (2011) · Drug Metabolism Reviews · doi:10.3109/03602532.2011.597401 · Cited by 78
(2001) · Indian Journal of Pharmacology · Cited by 52
Metadata
- Authors
- Watkins, P. B., Wrighton, S. A., Schuetz, E. G., Molowa, D. T., & Guzelian, P. S.
- Venue
- Journal of Clinical Investigation
- Published
- 1987-10-01
- Volume
- 80
- Issue
- 4
- Pages
- 1029-1036
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2073965718
- Cited by
- 480
- References
- 0
- FWCI
- 5.33
- Type
- journal article
- Language
- en
- Open access
- bronze
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