The influence of epinephrine on prostacyclin (PGI2) induced dissociation of ADP aggregated plateletes.
Prostacyclin (PGI2) is a powerful inhibitor of platelet function and recent studies have indicated that it can dissociate aggregated platelets in vivo. The present investigation has evaluated the mechanism involved in the dissociation of ADP aggregated platelets by PGI2, the influence of epinephrine on the process of PGI2 mediated disaggregation, and effects of the catecholamine on the refractory state of PGI2 dispersed cells. Dissociation of ADP aggregates by PGI2 was concentration and time dependent, caused complete disappearance of sensitive platelet clumps and restored platelet discoid form. The dispersed platelets were refractory to further stimulation by ADP, thrombin, arachidonate or the calcium ionophore, A23187. Measurement of cAMP revealed no change in control levels after aggregation by ADP, but a sharp increase during and after dissociation by PGI2. Epinephrine added to ADP aggregates before or after PGI2 blocked disaggregation, or stopped dissociation if already in progress, and caused a rapid fall in the high levels of cAMP stimulated by PGI2. Agents to which PGI2 dissociated platelets were refractory, including ADP, arachidonate and A23187 caused no lowering of elevated cAMP levels. Reduction of high levels of cAMP in PGI2 dispersed platelets by epinephrine did not result in reaggregation. However, epinephrine addition to refractory platelets restored in large measure their sensitivity to aggregation by arachidonate, thrombin, ADP and A23187.
D000244:Adenosine Diphosphate / Q000494:pharmacology*; D000328:Adult; D000242:Cyclic AMP / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology*; D011464:Epoprostenol / Q000494:pharmacology*; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects*; D011453:Prostaglandins / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism
D011453:Prostaglandins; D012701:Serotonin; D000244:Adenosine Diphosphate; D011464:Epoprostenol; D000242:Cyclic AMP; D004837:Epinephrine