Linked Life Data

9252148

Source:http://linkedlifedata.com/resource/pubmed/id/9252148

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1997-8-28
pubmed:abstractText
To assess the effect of side chain length on the metabolism and physiological effects of homologues of chenodeoxycholic acid (CDCA), dinorCDCA, the C22 homologue, was synthesized and its hepatic biotransformation, transport kinetics, and choleretic properties were defined in rat and hamster biliary fistula and in isolated perfused rat liver. Results were compared with those of norCDCA, the C23 homologue, and of CDCA, the natural C24 homologue. In the rat, dinorCDCA was secreted mostly in unconjugated form (the majority as dinor-alpha-muricholic acid); the remainder was glucuronidated. In the hamster, glucuronidation was greater, and the unconjugated fraction contained equal parts of dinorCDCA and 5beta-hydroxy-dinorCDCA. NorCDCA was glucuronidated extensively (70%, rat; 40%, hamster). CDCA, in contrast, was efficiently amidated with taurine or glycine. In the perfused liver, the initial uptake rate of all three homologues was identical; later, regurgitation and/or cholehepatic shunting of dinorCDCA and norCDCA, but not of CDCA, occurred. In rats and hamsters with biliary fistulas, dinorCDCA and norCDCA, but not CDCA, induced a bicarbonate-rich hypercholeresis of canalicular origin. Hypercholeresis was not induced by the taurine conjugate of dinorCDCA. Hepatobiliary retention of both dinorCDCA and norCDCA occurred, consistent with efficient ductular absorption (calculated to be 94%) and cholehepatic cycling of the unmetabolized bile acids. It is concluded that dinorCDCA, as norCDCA, is inefficiently amidated, is metabolized as a xenobiotic, and induces hypercholeresis. DinorCDCA is the first dihydroxy bile acid to be identified that is secreted largely in unconjugated form in bile.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0270-9139
pubmed:author
pubmed:issnType
Print
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
374-85
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Effect of side chain length on biotransformation, hepatic transport, and choleretic properties of chenodeoxycholyl homologues in the rodent: studies with dinorchenodeoxycholic acid, norchenodeoxycholic acid, and chenodeoxycholic acid.
pubmed:affiliation
Department of Medicine, University of California San Diego, La Jolla 92093-0813, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't