Metabolic aspects of the secretion of stored compounds from blood platelets IV. Effects of ionophore X537A on washed platelets

Abstract

1. 1. X537A at concentrations below 10 μM can liberate platelet serotonin from washed human platelets without inducing the platelet release reaction. Up to 100% of serotonin preabsorbed by the platelets can be liberated before initiation of the release reaction. 2. 2. Concentrations of X537A above 10 μM initiate the platelet release reaction, with a maximum release of adenine nucleotides and platelet factor 4 antigen comparable to that obtained with 1.25 units thrombin/ml. 3. 3. The changes in ATP metabolism at the concentration necessary for X537A-induced release are more profound than those in platelets exposed to concentrations of thrombin or A23187 giving the same degree of release, and approach those seen with high concentrations of A23187. At concentrations where serotonin is liberated but no adenine nucleotide or platelet factor 4 antigen is released, short time incubation causes no change in the level of metabolic ATP. 4. 4. In Na + medium the release increases with prolonged incubation to a level which seems to be characteristic for a particular ionophore concentration. Replacing Na + with K + in the incubation medium produces the maximum release for a particular concentration after short-time incubation, and no further increase is see. 5. 5. When platelets are incubated with antimycin and glucose so that anaerobic metabolism is predominant and then exposed to X537A, a marked sparing effect on ATP utilization can be observed in K + medium, and an increased ATP breakdown in Na + medium. The shift in monovalent cation does not affect the amount liberated and released. 6. 6. We conclude that the increased speed of release induction and of liberation of serotonin reflects a direct effect of the ion change on the ionophore action, possibly by increasing the speed by which X537A is accumulated in the platelet membrane.