The influence of pH on aggregation of human washed platelets induced by thrombin or collagen

The anti-aggregating activity of L-arginine and its analogues has been investigated in washed human platelets. The ability of these compounds to inhibit platelet aggregation induced by thrombin or collagen was mimicked by a change in the external pH of the buffer from pH 8.0 to pH 7.4. Of the several analogues tested, only benzoyl-L-arginine ethylester (BAEE) inhibited thrombin- but not collagen-induced platelet aggregation. In platelet-rich plasma, BAEE also inhibited platelet aggregation without inhibiting fibrin clot formation. These results suggest that the marked sensitivity of washed human platelets to small changes in the external pH may lead to misinterpretation of the anti-aggregatory potency of protonated test drugs. For work with human washed platelets a physiological salt solution with more buffering capacity than Krebs-bicarbonate (such as Tyrode-HEPES) is recommended.