title: Metabolic enzyme activities and drug excretion in the small intestine and in the liver in the rat.
abstract: The aim of these experiments was the investigation of the correlation between the metabolic enzyme activities and the intestinal and hepatic excretion of p-nitrophenol (PNP) and its metabolites (PNP-glucuronide: PNP-G and PNP-sulfate: PNP-S) in the same group of rats (n = 10). A jejunal loop was perfused with isotonic medium containing PNP in a concentration of 500 μM. The samples were obtained from the luminal perfusion medium and from the bile. For enzyme assays tissue samples were obtained from the liver and jejunum at the end of experiments. Significant differences were calculated by the Student's t-test. The activity of UDP-glucuronyltransferase and sulfotransferase was about three times higher in the liver than in the small intestine. The activity of the ß-glucuronidase was about six times higher, the activity of the arylsulfatase was approximately seven times greater in the liver than in the jejunum. No significant difference was found between the luminal appearance and the biliary excretion of PNP-G. Contrary to these findings, the biliary excretion of PNP-S was significantly higher than the luminal appearance of PNP-sulfate. It can be concluded that no direct correlation exists between the activity of metabolic enzymes and the excretion rate of PNP-metabolites in the liver and in the jejunal segment of the small intestine.
authors.affiliation: University of Pécs Institute of Pharmaceutical Chemistry, Medical Faculty Pécs Hungary.
authors.forename: A
authors.initials: A
authors.lastname: Almási
authors.forename: Sz
authors.initials: S
authors.lastname: Bojcsev
authors.forename: T
authors.initials: T
authors.lastname: Fischer
authors.forename: H
authors.initials: H
authors.lastname: Simon
authors.forename: P
authors.initials: P
authors.lastname: Perjési
authors.forename: Emil
authors.initials: E
authors.lastname: Fischer
mesh_terms: D000818:Animals; D001192:Arylsulfatases / Q000378:metabolism; D001646:Bile / Q000201:enzymology*; D001659:Biliary Tract / Q000201:enzymology; D004789:Enzyme Activation / Q000502:physiology; D005965:Glucuronates / Q000493:pharmacokinetics; D020723:Glucuronic Acid / Q000378:metabolism; D005966:Glucuronidase / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000378:metabolism; D008658:Inactivation, Metabolic / Q000502:physiology; D007583:Jejunum / Q000201:enzymology*; D008099:Liver / Q000201:enzymology*; D008297:Male; D009596:Nitrophenols / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D013431:Sulfates / Q000378:metabolism; D015238:Sulfotransferases / Q000378:metabolism
chemical_list: D005965:Glucuronates; D009596:Nitrophenols; D013431:Sulfates; C049288:p-nitrophenol glucuronide; D020723:Glucuronic Acid; D014453:Glucuronosyltransferase; D015238:Sulfotransferases; D001192:Arylsulfatases; D005966:Glucuronidase; C024836:4-nitrophenol
keywords: drug excretion; liver; metabolic enzymes; p-nitrophenol; rat; small intestine