EFFECTS OF L-ARGININE AND D-ARGININE AND SOME RELATED ESTERS ON THE CYTOSOLIC MECHANISMS OF ALPHA-THROMBIN-INDUCED HUMAN PLATELET ACTIVATION

1 In Fura-2 preloaded human platelets, the increase in cytosolic calci um induced by alpha-thrombin was reduced by some L- and D-arginine est er compounds the IC50 (mum) values of which were 7.4 for TAEE, 56.9 fo r 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 w hen platelets were pretreated with 100 mum N-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 pla telet Na+/H+ antiporter (amiloride-inhibitable, evaluated after cytoso lic nigericin-induced acidification) were modified by L- and D-arginin e esters, while the native amino acids were ineffective. 5 The inhibit ory effects of the L- and D-arginine esters on platelet activation app ear to be mainly due to their inhibitory effect on Na+/H+ antiporter.