Molecular Pharmacology, Vol 17, 356-361, Copyright © 1980 by the American Society for Pharmacology and Experimental Therapeutics

The Relationship between Extracellular pH and Control of Blood Platelet Serotonin Secretion

¹ School of Biological Sciences, University of California, Irvine, California 92717

Hydroxyl ions (OH^-) have been proposed as the permeant anions responsible for triggering serotonin release from blood platelets. This hypothesis is based on the observations that (i) platelets exhibit a much higher efficiency of secretion at pH 8.2 than at pH 6.8 and (ii) agents which block anion channels are inhibitors of release. We have investigated this mechanism by testing two predictions of the hypothesis. First, the model implies that the pH of the medium at the time of exocytosis is the determining factor in release. We have observed that platelets do secrete serotonin at pH 6.8 if they are pretreated with a secretagogue at pH 7.6. Second, the hypothesis predicts that the actions of OH^- should be confined to the interior of the secretory granule. We have found this not to be the case, since the cellular processes of shape change and protein phosphorylation, neither of which is confined to granules, are markedly dependent on extracellular pH. These results demonstrate that hydroxyl ions affect platelets at a more general and probably earlier stage of activation than would be required by the "hydroxyl as permeant ion" hypothesis.