Cyclic AMP inhibits platelet activation independently of its effect on cytosolic free calcium |
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| Authors: | A Pannocchia R M Hardisty |
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| Institution: | Department of Haematology and Oncology, Institute of Child Health, The Hospital for Sick Children, Great Ormond Street, London WClN 3JH, UK |
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| Abstract: | Stimulation of platelets with the ionophore A23187, thrombin, ADP or PAF-acether resulted in a rapid increase of cytosolic free Ca2+, as measured with Quin-2, and in aggregation, 5HT secretion and - in the case of the first two agonists - thromboxane generation. PGI2 and dibutyryl cyclic AMP inhibited all these responses, except in the case of A23187, in response to which the increase in Ca2+ was unaffected, although the other responses were inhibited. The inhibition of aggregation and secretion in response to the combination of thrombin and A23187 was indistinguishable from that in response to thrombin alone. It thus appears that cAMP inhibits these responses independently of its effect in lowering cytosolic free Ca2+. |
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| Keywords: | DG 1 2-diacylglycerol InsP inositol1 4 5-trisphospate cAMP adenosine 3′5′-cyclic monophosphate dBcAMP dibutyryl cAMP PAF-acether TPA PI phosphatidylinositol |
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