STUDIES ON THE EFFECTS OF AGONISTS AND ANTAGONISTS ON PLATELET SHAPE CHANGE AND PLATELET-AGGREGATION IN WHOLE-BLOOD

The shape change that occurs when platelets are stimulated with an ago nist can be quantitated by monitoring changes in their forward-scatter /side-scatter profile using a now cytometer. Here we have stimulated p latelets in citrated whole blood with several agonists and determined the time-course and extent of the shape change that occurs. In some ex periments parallel investigations of shape change and aggregation were performed. Aggregation was measured by monitoring the fall in number of single platelets using a Whole Blood Platelet Counter. Some agents (ADP, PAF, U46619 and 5HT) produced a strong and rapid change in plate let forward-scatter/side-scatter that was maximal within 10 s. Others (A23187 and collagen) produced a strong but slower response. Adrenalin e produced only a weak response that was also slow to develop, and PMA did not produce any response. The concentrations of each of ADP, PAF, U46619 and 5HT needed to induce a shape change were lower than those required for aggregation. Selective PAF, TXA(2) and 5HT antagonists (W EB 2086, sulotroban and MCI-9042) clearly inhibited both the shape cha nge and the aggregation induced by the appropriate agonist; in each ca se the effect of the antagonist was to move the dose-response curve to the right. These results are consistent with the shape change and agg regation brought about by each of these agonists being mediated via a single receptor. In contrast, a selective P-2T purinoceptor antagonist (ARL 66096) markedly inhibited the aggregation induced by ADP but was found to have little or no effect on shape change. This is consistent with these platelet responses to ADP being mediated by different rece ptors, with P-2T receptors mediating only the aggregation response.