Involvement of cyclic GMP in the mode of action of a new antithrombotic agent PCA-4230; inhibition of the platelet cyclic GMP dependent phosphodiesterase.
Thromb Res
; 87(6): 547-57, 1997 Sep 15.
Article
en En
| MEDLINE
| ID: mdl-9330437
The effect of PCA-4230, a new dihydropyridine derivative with a potent antithrombotic activity, on cyclic nucleotide phosphodiesterase in platelets was studied. PCA-4230 inhibited (54%) cyclic GMP hydrolytic activity of a platelet cytosolic fraction, whereas it did not affect that of cyclic AMP. Results suggested that PCA-4230 inhibited a cyclic GMP-dependent phosphodiesterase, known as cGB PDE or type V, on a purified enzyme from rabbit platelets by a non-competitive-uncompetitive type inhibition. In addition, PCA-4230 potentiated the increase in both cyclic GMP and cyclic AMP levels evoked by sodium nitroprusside. Furthermore, PCA-4230 and forskolin caused a synergistic effect in cyclic AMP, and also potentiated the phosphorylation of 50 kDa and 22 kDa proteins, reported as substrates of cyclic GMP- and cyclic AMP-dependent protein kinases that are related to the inhibition of platelet functions. Finally, PCA-4230 also potentiated the forskolin- and sodium nitroprusside-inhibited serotonin release evoked by thrombin, probably related to the increased cyclic nucleotide level.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Plaquetas
/
Dihidropiridinas
/
GMP Cíclico
/
Fibrinolíticos
Límite:
Animals
Idioma:
En
Revista:
Thromb Res
Año:
1997
Tipo del documento:
Article
País de afiliación:
España
Pais de publicación:
Estados Unidos