Effects of two methylxanthines, pentoxifylline and propentofylline, on arachidonic acid metabolism in platelets stimulated by thrombin.
Biochem Pharmacol
; 37(17): 3229-36, 1988 Sep 01.
Article
em En
| MEDLINE
| ID: mdl-2840908
[3H]Pentoxifylline and [3H]propentofylline were taken up by human platelets in a dose-dependent manner probably involving a passive diffusion through the plasma membrane. In vitro, the two drugs were able to inhibit platelet activation induced by thrombin. serotonin secretion was reduced from 57% to 38% and 28% in the presence of 1 mM pentoxifylline and 1 mM propentofylline, respectively. Platelet aggregation was inhibited in the same way. Modifications of [14C]arachidonic acid metabolism in human platelets stimulated by thrombin were then measured in the presence of drugs. Preincubation of platelets with 1 mM pentoxifylline or propentofylline inhibited the production of [14C]arachidonic acid metabolites, without any accumulation of free arachidonic acid, suggesting an action at a step preceding its conversion. Phosphatidylinositol and phosphatidylcholine hydrolysis measured upon thrombin treatment as well as phosphatidic acid production were reduced or suppressed in the presence of the drugs. A dose-dependence study showed that phosphatidylcholine hydrolysis was totally inhibited at 5.10(-4) M propentofylline, while phosphatidic acid formation was reduced by only 40%. Propentofylline was in general more efficient than pentoxifylline in inhibiting events occurring upon thrombin stimulation. Our results suggest that the two methylxanthines inhibit both phospholipase A2 and phospholipase C, the former displaying a greater sensitivity to the two drugs.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pentoxifilina
/
Teobromina
/
Xantinas
/
Plaquetas
/
Trombina
/
Ácidos Araquidônicos
Limite:
Humans
Idioma:
En
Revista:
Biochem Pharmacol
Ano de publicação:
1988
Tipo de documento:
Article