Lack of evidence for a role for the lipoxygenase pathway in increases in cytosolic calcium evoked by ADP and arachidonic acid in human platelets.
We have investigated the possibility that metabolism of arachidonic acid by the lipoxygenase pathway contributes to ADP-evoked rises in [Ca2+], in human platelets. 30 microM BW A4C did not affect ADP-evoked Ca2+ signals, but inhibited 12-lipoxygenase activity in platelet homogenates. Another lipoxygenase inhibitor, MK 866 was similarly without effect on ADP-evoked Ca2+ signals. ADP was found to liberate little arachidonic acid, and formation of the lipoxygenase product 12-HETE was not detectable. The rise in [Ca2+]i evoked by arachidonic acid was completely inhibited by the cyclooxygenase inhibitors aspirin or indomethacin. These results indicate that lipoxygenase products do not play an essential role in mediating rises in [Ca2+]i evoked by ADP, or by arachidonic acid.
Vindlacheruvu
R R
RR
Physiological Laboratory, University of Cambridge, UK.
Rink
T J
TJ
Sage
S O
SO
D000244:Adenosine Diphosphate / Q000378:metabolism*; D000345:Affinity Labels; D016718:Arachidonic Acid / Q000378:metabolism*; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors; D003600:Cytosol / Q000378:metabolism*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D016257:Fura-2 / Q000737:chemistry; D006801:Humans; D008084:Lipoxygenase / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors
D000345:Affinity Labels; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D016718:Arachidonic Acid; D004533:Egtazic Acid; D000244:Adenosine Diphosphate; D008084:Lipoxygenase; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium; D016257:Fura-2