Platelet Shape Change Evoked by Selective Activation of P2X₁ Purinoceptors with α,β-Methylene ATP

Summary

Simultaneous measurements of [Ca²⁺]_i and light transmission were used to examine the relationship between P2X₁ receptor activation and functional platelet responses. The P2X₁ agonist α,β-MeATP evoked a transient [Ca²⁺]_i increase and a reversible decrease in light transmission; both responses required external Ca²⁺ and the nucleotidase apyrase. The transmission response was due to shape change only, verified by scanning electron microscopy and insensitivity to Reopro, a GPIIbIIIa antagonist. α,β-MeATP stimulated smaller shape changes than ADP, however P2X₁ responses had a lifespan of <2 h following resuspension in saline and may be considerably larger in vivo. A peak [Ca²⁺]_i increase of >50 nM was required for detectable shape change. Overlap of concentration-response relationships for α,β-MeATP-evoked [Ca²⁺]_i and shape change suggests that other second messengers are not involved. Therefore, the physiological P2X₁ agonist ATP can contribute to platelet activation, in contrast to its previously described inhibitory action at metabotropic platelet purinoceptors.

Keywords

Platelets - P2X receptors - ATP - purinoceptors - shape change

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