Evidence for control of serotonin secretion from human platelets by hydroxyl ion transport and osmotic lysis.
Serotonin secretion from human platelets, stimulated either by thrombin or the calcium ionophore A23187, was found to be inhibited by anion transport blocking drugs such as 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS), pyridoxal phosphate, probenecid, and suramin. These drugs have previously been shown to inhibit ATP-evoked release of epinephrine from isolated chromaffin granules by blocking chloride uptake and subsequent osmotic lysis. However, in contrast to granule release, platelet secretion was insensitive to chloride and, instead, was dependent on OH-. Platelet release was suppressed by low pH, and inhibition by the transport blocking drugs was competitive only with respect to OH-. Serotonin release from platelets was also suppressed by increasing extracellular osmotic strength, and the relationship between suppression and external osmotic strength was quantitatively similar to that observed in the case of chromaffin granules. We conclude that platelet exocytosis could occur when serotonergic granules are closely juxtaposed to the plasma membrane, thus exposing the granule anion transport site to the more alkaline medium. Secretion of serotonin could occur as a consequence of OH- transport and osmotic lysis of the granule-plasma membrane complex, analogous to the chemiosmotic mechanism of chloride-dependent epinephrine release from isolated chromaffin granules.
Evidence for control of serotonin secretion from human platelets by hydroxyl ion transport and osmotic lysis. Serotonin secretion from human platelets, stimulated either by thrombin or the calcium ionophore A23187, was found to be inhibited by anion transport blocking drugs such as 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS), pyridoxal phosphate, probenecid, and suramin. These drugs have previously been shown to inhibit ATP-evoked release of epinephrine from isolated chromaffin granules by blocking chloride uptake and subsequent osmotic lysis. However, in contrast to granule release, platelet secretion was insensitive to chloride and, instead, was dependent on OH-. Platelet release was suppressed by low pH, and inhibition by the transport blocking drugs was competitive only with respect to OH-. Serotonin release from platelets was also suppressed by increasing extracellular osmotic strength, and the relationship between suppression and external osmotic strength was quantitatively similar to that observed in the case of chromaffin granules. We conclude that platelet exocytosis could occur when serotonergic granules are closely juxtaposed to the plasma membrane, thus exposing the granule anion transport site to the more alkaline medium. Secretion of serotonin could occur as a consequence of OH- transport and osmotic lysis of the granule-plasma membrane complex, analogous to the chemiosmotic mechanism of chloride-dependent epinephrine release from isolated chromaffin granules.