Linked Life Data

2161922

Source:http://linkedlifedata.com/resource/pubmed/id/2161922

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1990-7-16
pubmed:abstractText
Selectivity of captopril, enalapril (MK-421), enalaprilat (MK-422), ketoace, and SA-300 for inhibiting kininase II when angiotensin (ANG) I versus bradykinin (BK) is the substrate has been studied in vitro. Potency for inhibiting purified rabbit lung ANG I-converting enzyme (ACE) using a tripeptide substrate with an ANG I-like (hippurylhistidylleucine, HHL) or a BK-like (hippurylphenylalanylarginine, HPA) cleavable dipeptide was determined. Inhibition of ANG I-induced and potentiation of BK-induced contractions of isolated guinea pig ileum strips was measured. For the enzyme assay, the inhibitor concentration which reduced the rate of HHL and HPA hydrolysis 50% (IC50) from the control value was estimated. All tested compounds more potently inhibited hydrolysis of the ANG I-related tripeptide by the purified enzyme. Ketoace, with a selectivity ratio (HPA IC50:HHL IC50) of 23, was the most substrate-dependent inhibitor. For the isolated ileum assay, the inhibitor concentration which augmented the contractile response to BK by 50% (AC50) or inhibited the contractile response to ANG I by 50% (IC50) was calculated. Only enalaprilat retained a selectivity ratio (BK AC50:ANG I IC50) in the guinea pig ileum system greater than one. Ketoace, with a ratio of 0.038, was the least ANG I-selective by this criterion. In vivo selectivity data on captopril seem more in accord with the ileum, rather than the enzyme, results. It was concluded that converting enzyme inhibitors differ in their relative selectivity for inhibiting kininase II reactions using different substrates.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-3549
pubmed:author
pubmed:issnType
Print
pubmed:volume
79
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
384-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1990
pubmed:articleTitle
Selectivity of converting-enzyme inhibitors for angiotensin I versus bradykinin hydrolysis reactions.
pubmed:affiliation
Norwich Eaton Pharmaceuticals, Inc., NY 13815-0191.
pubmed:publicationType
Journal Article, In Vitro