A major role for P2X1 receptors in the early collagen-evoked intracellular Ca2+ responses of human platelets.
In the platelet, ATP-gated P2X1 receptors have been reported to amplify functional responses to collagen, however the relative importance of early CCa2+ mobilisation events is unknown. We now report that selective desensitisation of P2X1 receptor activity leads to a major reduction in the initial intracellular Ca2+ responses to a wide range of collagen concentrations (0.25-2 microg ml(-1)). Peak [Ca2+](i) increases were reduced to 8.5 and 55% of control, and the maximum rate of rise was reduced to 12 and 33% of control, at low and high collagen concentrations, respectively. This P2X1-dependent acceleration and enhancement of collagen-stimulated Ca2+ responses was not observed in the absence of extracellular Ca2+. These results demonstrate a major role for ATP-gated Ca2+ influx in the early collagen-evoked Ca2+ signals and can at least partly explain the important contribution of P2X1 receptors to arterial thrombosis.
Fung
C Y Eleanor
CY
Department of Physiology, University of Cambridge, Cambridge, CB2 3EG, UK.
Brearley
Charles A
CA
Farndale
Richard W
RW
Mahaut-Smith
Martyn P
MP
D000255:Adenosine Triphosphate / Q000737:chemistry; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D002118:Calcium / Q000737:chemistry / Q000378:metabolism*; D002417:Cattle; D003094:Collagen / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D058469:Receptors, Purinergic P2X; D013050:Spectrometry, Fluorescence; D013710:Tendons / Q000378:metabolism; D020246:Venous Thrombosis / Q000473:pathology
D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; D000255:Adenosine Triphosphate; D003094:Collagen; D002118:Calcium