Platelet shape change evoked by selective activation of P2X1 purinoceptors with alpha,beta-methylene ATP.
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 alpha,beta-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. Alpha,beta-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 alpha,beta-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.
Department of Physiology, University of Cambridge, UK.
M G
MG
Rolf
C A
CA
Brearley
M P
MP
Mahaut-Smith
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D001792:Blood Platelets / Q000166:cytology*; D020013:Calcium Signaling / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes; D016257:Fura-2; D006801:Humans; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D015539:Platelet Activation / Q000187:drug effects*; D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D058469:Receptors, Purinergic P2X
D005456:Fluorescent Dyes; D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D016257:Fura-2