Linked Life Data

10604966

Source:http://linkedlifedata.com/resource/pubmed/id/10604966

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2000-1-27
pubmed:abstractText
Xanthine oxidoreductase (XOR) is a mammalian enzyme that possesses a series of redox centers, which use either NAD(+) or molecular oxygen for oxidation of the purines xanthine and hypoxanthine to uric acid. The ability of XOR to act as an NADH oxidase is a less well recognized function of the enzyme, and it is this function that we used to explore the metabolism of glyceryl trinitrate. The antiplatelet effect of nitric oxide (NO) on platelet aggregation was used as a bioassay to assess the bioconversion of glyceryl trinitrate to NO by XOR. The thromboxane mimetic U46619, 2 microM, was used to stimulate platelet aggregation in platelet-rich plasma prepared from healthy drug-free human volunteers. All incubations were carried out at 37 degrees C for 2 min after the addition of U46619. XOR produced a dose-dependent antiaggregant effect when incubated with glyceryl trinitrate (GTN), 220 microM. This did not occur when GTN or XOR was incubated with platelet-rich plasma independently. The antiaggregant effect of XOR plus GTN was dose dependently inhibited by allopurinol, with an IC(50) of 100 microM. The addition of superoxide dismutase (SOD), 100 U/ml produced a shift to the left in the antiaggregant dose-response curve for XOR. The IC(50) for XOR at 200 U/l without SOD was decreased to 80 U/l with SOD. Oxyhemoglobin, an extracellular NO scavenger, produced a dose-dependent, noncompetitive inhibition of the antiaggregant effect of XOR plus GTN. These findings suggest that GTN may be reduced to NO in vitro by the enzyme XOR in sufficient amounts to inhibit platelet aggregation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
292
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
326-30
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Inhibition of platelet aggregation with glyceryl trinitrate and xanthine oxidoreductase.
pubmed:affiliation
Clinical Pharmacology, St. Bartholomew's and the Royal London School of Medicine and Dentistry, London, United Kingdom. S.R.O'Byrne@mds.qmw.ac.uk
pubmed:publicationType
Journal Article, In Vitro