MICROBUBBLE-INDUCED PHOSPHOLIPASE-C ACTIVATION DOES NOT CORRELATE WITH PLATELET-AGGREGATION

The effect of nitrogen-(N2-)microbubbles on platelets resembles that o f common platelet agonists with respect to aggregation and secretion, but is considerably slower and is poorly inhibited by aspirin. This pa per reports the effect of microbubbles on platelet phospholipase C act ivity in gelfiltered human platelets prelabelled with [P-32]P(i) ([P-3 2]-GFP). The experiments were run in the presence of an ADP scavenging system in order to rule out effects of ADR Stimulation of [P-32]-GFP for 30 min with microbubbles caused a significant reduction in single platelets (p <0.0004) and a significant increase in P-32-activity in t he phosphatidic acid (PA) fraction (p < 0.02). Epinephrine potentiated the microbubble-induced reduction in single platelets (p <0.05), but did not enhance the amount of P-32 in the platelet [P-32]PA fraction. The P-32-radioactivity in the PI-fraction increased with time to a sim ilar extent when [P-32]-GFP was stirred for 30 min in absence of micro bubbles as it did after 30 min of agonist exposure. There were no sign ificant changes in the [P-32]PIP and [P-32]PIP2 fractions. Aspirin abo lished the microbubble-induced increase in P-32-activity in the PA fra ction, but had no significant effect on the reduction in single platel ets. Aspirin had a small but significant, reducing effect on platelet aggregation induced by a combination of epinephrine and microbubbles ( p < 0.05). With epinephrine, however, aspirin did not completely aboli sh the increase in [P-32]-PA. It is concluded that microbubbles alone cause platelets to aggregate by a novel mechanism that operates indepe ndent of cyclooxygenase-dependent arachidonic acid metabolites and pho spholipase C activation.