Adrenaline and PAF-acether synergize to trigger cyclooxygenase-independent activation of plasma-free human platelets

Platelet-activating factor (PAF-acether, 1-0-octadecyl-2-acetyl-sn-glyceryl-3-phosphorylcholine), a potent aggregating agent for the platelets in plasma, induced only a moderate aggregation of plasma-free suspensions of human platelets. By contrast, addition of PAF-acether plus adrenaline or ADP to the platelet suspension was followed by full aggregation, accompanied by a moderate secretion of ATP. This synergism was observed better in the presence of fibrinogen, but was also seen in its absence when using the combination of PAF-acether with adrenaline. Aspirin failed to interfere with the synergized aggregation, ruling out a role for cyclooxygenase. The order of addition of adrenaline and of PAF-acether to the platelets was critical. When the former was added first to the platelets suspension, aggregation was induced by the latter even if added after one hour. Conversely, aggregation was only induced by adrenaline added after PAF-acether, if the interval between both was of around one minute. Removal of ADP with the scavenging system creatine phosphate/creatine phosphokinase prevented the synergism between PAF-acether plus ADP, but failed to interfere with that induced by PAF-acether plus adrenaline. The synergized aggregation induced by adrenaline or ADP and PAF-acether may represent a novel mechanism, accounting for the increased aggregability under various physiopathological conditions.