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Mechanism of inhibition of cyclo-oxygenase in human blood platelets by carbamate insecticides.
Biochem. J. 250, 103-110 (1988)
Carbamates are a widely used class of insecticides and herbicides. They were tested for their ability to affect human blood platelet aggregation and arachidonic acid metabolism in platelets. (1) The herbicides of the carbamate type have no, or only little, influence up to a concentration of 100 μM; the carbamate insecticides, however, inhibit both aggregation and arachidonic acid metabolism in a dose- and time-dependent manner. (2) Carbaryl, the most effective compound, inhibits platelet aggregation and cyclo-oxygenase activity completely at 10 μM. The liberation of arachidonic acid from phospholipids and the lipoxygenase pathway are not affected, whereas the products of the cyclo-oxygenase pathway are drastically decreased. (3) By using [14C]carbaryl labelled in the carbamyl or in the ring moiety, it could be proved that the carbamyl residue binds covalently to platelet proteins. In contrast with acetylsalicylic acid, which acetylates only one protein, carbaryl carbamylates a multitude of platelet proteins. (4) One of the carbamylated proteins was found to be the platelet cyclo-oxygenase, indicating that carbaryl resembles in this respect acetylsalicylic acid, which is known to inhibit this enzyme specifically by acetylation.
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Publication type
Article: Journal article
Document type
Scientific Article
ISSN (print) / ISBN
0264-6021
e-ISSN
1470-8728
Journal
Biochemical Journal / Reviews
Quellenangaben
Volume: 250,
Issue: 1,
Pages: 103-110
Publisher
Portland Press
Reviewing status
Peer reviewed
Institute(s)
Institut für Toxikologie und Biochemie