Agents that elevate the concentration of cAMP in platelets inhibit the formation of a NaDodSO4-resistant complex between thrombin and a 40-kDa protein.

We studied the influence of prostaglandin E1 and theophylline on the ability of rabbit or human platelets to form NaDodSO4-resistant complexes between 125I-labeled thrombin and a platelet protein of approximately equal to 40 kDa. Control platelets formed two types of these complexes, one that sedimented with the platelets and one that was found in the suspension medium. There were 30-40 sedimentable complexes per platelet and about three times this number of soluble complexes. Pretreatment of rabbit or human platelets with prostaglandin E1 and theophylline decreased the formation of both types of complex by as much as 60-80%. The pretreatment was particularly effective when low doses of thrombin were used. When added to control platelets, such doses of thrombin caused the formation of sedimentable complexes and the concomitant formation of inositol trisphosphate. However, when added to platelets that had been pretreated with prostaglandin E1 and theophylline, low doses of thrombin had little or no effect on either reaction.