Journal Article
Effects of l-arginine and d-arginine and some related esters on the cytosolic mechanisms of alpha-thrombin-induced human platelet activation
Failli, P; Cecchi, E; Ruocco, C; Fazzini, A; Giotti, A
British Journal of Pharmacology
ISSN: 0007-1188
EISSN: 1476-5381
1. In Fura-2 preloaded human platelets, the increase in cytosolic calcium induced by alpha-thrombin was reduced by some L- and D-arginine ester compounds the IC50 (microM) values of which were 7.4 for TAEE, 56.9 for BAEE, 77.6 for TAME, 560 for T(d)AME, 656.3 for L-ArgOMe and 2206.7 for D-ArgOMe. alpha-tosyl-L-Arginine, L- and D-arginine were inactive. 2. The inhibitory activity of the L-arginine esters was not modified when platelets were pretreated with 100 microM N omega-monomethyl-L-arginine. 3. The L-arginine esters did not increase cyclic GMP content in platelets either in the presence or absence of indomethacin and apyrase at rest and after alpha-thrombin stimulation. 4. The kinetic parameters of platelet Na+/H+ antiporter (amiloride-inhibitable, evaluated after cytosolic nigericin-induced acidification) were modified by L- and D-arginine esters, while the native amino acids were ineffective. 5. The inhibitory effects of the L- and D-arginine esters on platelet activation appear to be mainly due to their inhibitory effect on Na+/H+ antiporter.
human platelets; alpha-thrombin activation; cytosolic calcium concentration; na+/h+ antiporter activity; l-arginine; d-arginine; l-arginine esters; d-arginine esters; n-omega-monomethyl-l-arginine
