Complex pattern of inhibition by Mg 2+ of exocytosis from permeabilised eosinophils

Abstract

Inhibition by Mg 2+ ions of exocytotic secretion from permeabilised eosinophils, stimulated by Ca 2+ and GTPγS, and in the presence and absence of ATP, has been examined. While Mg 2+ inhibits release of aryl sulphatase, hexosaminidase and peroxidase, we found no evidence that this occurs by competition at a Ca 2+-binding site. On the other hand, the IC 50 for Mg 2+ approximates a simple inverse relationship to EC 50 for GTPγS over a wide range of concentrations, indicative of a possible competition with events directly controlled by a GTP-binding protein. However, for secretion stimulated by GTPγS in the absence of Ca 2+ (which necessitates provision of ATP), the effect of Mg 2+ becomes biphasic. Initially, secretion is dependent on the presence of Mg 2+ as a component of the complex ligand Mg.ATP. At high concentrations, Mg 2+ inhibits secretion and the IC 50 was found to be fixed at a concentration of about 8 mM regardless of the strength of the stimulus. The presence of ATP appears to divert the site of inhibition due to Mg 2+.