Identification of glucocorticoid-inducible cytochromes P-450 in the intestinal mucosa of rats and man.
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.
Watkins
P B
PB
Department of Medicine, Medical College of Virginia, Richmond 23298.
Wrighton
S A
SA
Schuetz
E G
EG
Molowa
D T
DT
Guzelian
P S
PS
D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004247:DNA / Q000032:analysis; D003907:Dexamethasone / Q000494:pharmacology*; D004790:Enzyme Induction; D004917:Erythromycin / Q000378:metabolism; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology* / Q000648:ultrastructure; D007527:Isoenzymes / Q000096:biosynthesis*; D007583:Jejunum / Q000201:enzymology / Q000648:ultrastructure; D008297:Male; D008861:Microsomes / Q000201:enzymology; D008862:Microsomes, Liver / Q000201:enzymology; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000911:Antibodies, Monoclonal; D007527:Isoenzymes; D012333:RNA, Messenger; D004917:Erythromycin; D003907:Dexamethasone; D004247:DNA; D003577:Cytochrome P-450 Enzyme System