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Release of 14C-serotonin during initial platelet changes induced by thrombin, collagen, or A23187

1977; Elsevier BV; Volume: 50; Issue: 5 Linguagem: Inglês

10.1182/blood.v50.5.915.915

1528-0020

MA Packham, MA Guccione, J. Greenberg, RL Kinlough-Rathbone, J. F. Mustard,

Platelet Disorders and Treatments

Release of 14C-serotonin from prelabeled platelets during the lag phase before aggregation and during aggregation caused by low concentrations of thrombin, collagen, or A23187 was measured after stopping release instantaneously with paraformaldehyde. Imipramine was used to prevent reuptake of released serotonin. At the lowest point on the light transmission curve following the addition of thrombin, release of 14C-serotonin was barely detectable, although 5%-10% of the platelets were seen to be aggregated in pairs or triplets upon microscopic examination. The lag phase was slightly prolonged by creatine phosphate/creatine Phosphokinase (CP/CPK), indomethacin, acetylsalicylic acid, or a combination of one of the drugs with CP/CPK; release at maximum aggregation was only partially reduced by these inhibitors. Thus thrombin appears to cause aggregation through at least three mechanisms: released adenosine diphosphate (ADP), formation of prostaglandin endoperoxides and thromboxane A2, and a third mechanism (not yet defined) which is the most dominant one. Collagen caused 1.9% release (representing 0.28 μM ADP) at the lowest point on the light transmission curve. This concentration of ADP is insufficient to cause aggregation by itself. Studies with the inhibitors showed that the lag phase was prolonged by CP/CPK, indomethacin, or acetylsalicylic acid; collagen-induced shape change and aggregation were completely blocked by a combination of CP/CPK and one of these drugs. Thus collagen-induced shape change and aggregation are largely dependent on two mechanisms: released ADP and products formed from platelet arachidonate. The ionophore A23187 caused 1.2% release (representing 0.18 μM ADP) at the point where aggregation began. Results with the inhibitors were similar to those with thrombin. Thus A23187 may also act through three mechanisms, the third probably caused by internal calcium shift(s). In no case was released ADP solely responsible for aggregation, but it acted synergistically with the other mechanisms to augment the extent of aggregation and release.