Linked Life Data

9531519

Source:http://linkedlifedata.com/resource/pubmed/id/9531519

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1998-5-14
pubmed:abstractText
Two possible sites of renal metabolism exist: intracellular, by enzymes within the peritubular cells, and intraluminal, by ecto-enzymes embedded on the brush border membrane. The esterolysis of enalapril to its dicarboxylate metabolite, enalaprilat, was studied in the isolated perfused, nonfiltering rat kidney preparation (NFK) and compared with that observed for the isolated perfused rat kidney (IPK) to ascertain the site of metabolic conversion. For the NFK, filtration was obliterated with the high oncotic pressure (8% bovine serum albumin in plasma) and ligation of the ureter, thus preventing enalapril from reaching intraluminal sites by filtration. The steady-state renal plasma clearance of enalapril in the NFK was 2.0 ml/min/g, a value similar to that (2.1 ml/min/g) observed previously for the IPK. The rate of appearance of enalaprilat, the metabolite, in venous plasma for the NFK (30 +/- 3% of the input rate of enalapril) was also comparable with that for the IPK (27 +/- 4%). Further, identification of the site of enalapril metabolism (cellular or luminal) was aided by simulations based on physiological models and parameters obtained previously on the renal handling of enalapril and enalaprilat. These parameters were optimized to match closely the experimental observations. The predicted total and metabolic renal clearances for the IPK or for the NFK were similar for both the "cellular model" and "luminal model": in both instances, values for the NFK were 59-65% of those for the IPK. By contrast, predictions for the venous output rate of enalaprilat (as a percent of the input rate of enalapril) were different: the "cellular model" predicted no change in value between the NFK and the IPK, whereas metabolite appearance was greatly magnified for the NFK (289% that of the IPK) with luminal metabolism. The lack of difference in venous outflow of enalaprilat for the NFK and IPK was more congruent with the notion of intracellular and not intraluminal esterolysis of enalapril.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0090-9556
pubmed:author
pubmed:issnType
Print
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
324-31
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Intracellular and not intraluminal esterolysis of enalapril in kidney. Studies with the single pass perfused nonfiltering rat kidney.
pubmed:affiliation
Department of Pharmacology, University of Toronto, Ontario, Canada.
pubmed:publicationType
Journal Article, Comparative Study, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't