COX-2 is not involved in thromboxane biosynthesis by activated human platelets.
J Physiol Pharmacol
; 50(4): 661-7, 1999 Dec.
Article
em En
| MEDLINE
| ID: mdl-10639016
The occurrence of aspirin resistance has been inferred by the assessment of platelet aggregation ex vivo in patients with ischemic vascular syndromes taking aspirin. Since aspirin is a weak inhibitor of the inducible isoform of prostaglandin H synthase (COX-2), it was suggested that COX-2 may play a role in aspirin resistance. However the cellular source(s) of COX-2 possibly responsible for aspirin resistance remains unknown. Recently, the expression of the inducible isoform of COX-2 in circulating human platelets was reported. To investigate the possible contribution of COX-2 expression in platelet thromboxane (TX) biosynthesis, we have compared the inhibitory effects of NS-398 and aspirin, selective inhibitors of COX-2 and COX-1, respectively, on prostanoid biosynthesis by thrombin-stimulated platelets vs lipopolysaccharide (LPS)stimulated monocytes (expressing high levels of COX-2) isolated from whole blood of healthy subjects. NS-398 was 180-fold more potent in inhibiting monocyte COX-2 activity than platelet TXB2 production. In contrast, aspirin (55 micromol/L) largely suppressed platelet TXB2 production without affecting monocyte COX-2 activity. By using specific Western blot techniques, we failed to detect COX-2 in platelets while COX-1 was readily detectable. Our results argue against the involvement of COX-2 in TX biosynthesis by activated platelets and consequently dispute platelet COX-2 expression as an important mechanism of aspirin resistance.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Plaquetas
/
Monócitos
/
Ativação Plaquetária
/
Prostaglandinas
/
Tromboxanos
/
Inibidores de Ciclo-Oxigenase
/
Prostaglandina-Endoperóxido Sintases
/
Isoenzimas
Limite:
Adult
/
Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
1999
Tipo de documento:
Article