Stimuli causing aggregation of platelets and their secretory release reaction are the most likely causes of thrombosis. Thrombin is the most powerful in vitro platelet stimulus thought to underlie in vivo thrombotic phenomena and to cause thrombocytopenia of disseminated intravascular clotting. We found that dogs given intravenous thrombin in variable doses could be completely defibrinated without causing thrombocytopenia platelet aggregation or thrombus formation, indicating that factors other than initiation of blood coagulation underlie thrombosis. Platelets in Bartter's syndrome were found to be poorly responsible to ADP aggregation and on EM appear to have abnormal vacuolization that may vary with electrolyte balance. Platelet secretion has many features in common with chromaffin cell secretion of catecholamines vasoactive intestinal polypeptide (VIP) and enkephalin; and both types of cells respond similarly to certain secretory agonists and inhibitors. Cultured chromaffin cells have been used to measure regulation of peptide secretion with respect to changes in transcription and translation utilizing mRNA and cDNA to evaluate effects of secretory stimuli and inhibitors on message formation. Tripeptide aldehyde protease inhibitors which inhibit thrombin were found to block catecholamine release in a manner similar to their inhibition of platelet release. A meperidine analog NMPTP, which causes a syndrome identical to Parkinsonism was found to kill cultured chromaffin cells over several days and to acutely cause release of catecholamines.

Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Arthritis, Diabetes, Digestive & Kid Dis
United States
Zip Code