Platelet shape change evoked by selective activation of P2X(1) purinoceptors with alpha,beta-methylene ATP

Simultaneous measurements of [Ca2+](i) and light transmission were used to examine the relationship between P2X(1) receptor activation and functional platelet responses. The P2X(1) agonist alpha,beta -MeATP evoked a transient [Ca2+](i) increase and a reversible decrease in light transmission: both r esponses required external Ca2+ and the nucleotidase apyrase. The transmiss ion response was due to shape change only, verified by scanning electron mi croscopy and insensitivity to Reopro, a GPIIbIIIa antagonist. alpha,beta -M eATP stimulated smaller shape changes than ADP, however P2X(1) responses ha d a lifespan of <2 h following resuspension in saline and may br considerab ly larger in vivo. A peak [Ca2+](i) increase of >50 nM was required for det ectable shape change. Overlap of concentration-response relationships for a lpha,beta -MeATP-evoked [Ca2+](i) and shape change suggests that other seco nd messengers are not involved. Therefore, the physiological P2X(1) agonist ATP can contribute to platelet activation, in contrast to its previously d escribed inhibitory action at metabotropic platelet purinoceptors.