No requirement of P2X1 purinoceptors for platelet aggregation.
ADP produces a series of responses in rabbit platelets such as shape changes, aggregation and intracellular Ca2+ mobilization. In human platelets, the P2X1 receptor mediates a rapid increase in intracellular Ca2+ concentration ([Ca2+]i) upon stimulation with ADP. We investigated whether this phenomenon is also present in rabbit platelets. We found that the P2X1 receptor-mediated response was absent because there was (1) no elevation of [Ca2+]i in response to alpha,beta-methylene-ATP, a selective P2X1 receptor agonist, in fura-2-loaded platelets; (2) no change in the ADP-induced [Ca2+]i increase and platelet aggregation after P2X1 receptor desensitization with alpha,beta-methylene-ATP; (3) complete inhibition of the ADP-induced [Ca2+]i elevation by the P2Y1 receptor specific antagonist, A3'P5'PS, with a similar ID50 value both in the presence and absence of external Ca2+. These results indicate that ADP-induced [Ca2+]i elevation is mainly mediated by P2Y1 receptors in rabbit platelets. We conclude that the P2X1 receptor does not play a significant role in the ADP-induced platelet shape changes and aggregation.
Department of Pharmacology, School of Medicine, Fukushima Medical University 1, Japan. s-takano@cc.fmu.ac.jp
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Takano
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Kimura
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Matsuoka
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Ono
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D005260:Female; D005456:Fluorescent Dyes; D016257:Fura-2; D066298:In Vitro Techniques; D008297:Male; D010724:Phosphoadenosine Phosphosulfate / Q000494:pharmacology; D010974:Platelet Aggregation; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D011817:Rabbits; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D058469:Receptors, Purinergic P2X; D058472:Receptors, Purinergic P2Y1
D005456:Fluorescent Dyes; C546382:P2RY1 protein, human; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; D058472:Receptors, Purinergic P2Y1; D010724:Phosphoadenosine Phosphosulfate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D002118:Calcium; D016257:Fura-2