Complex pattern of inhibition by Mg2+ of exocytosis from permeabilised eosinophils.
Inhibition by Mg2+ ions of exocytotic secretion from permeabilised eosinophils, stimulated by Ca2+ and GTP gamma S, and in the presence and absence of ATP, has been examined. While Mg2+ 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 IC50 for Mg2+ approximates a simple inverse relationship to EC50 for GTP gamma S 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 GTP gamma S in the absence of Ca2+ (which necessitates provision of ATP), the effect of Mg2+ becomes biphasic. Initially, secretion is dependent on the presence of Mg2+ as a component of the complex ligand Mg.ATP. At high concentrations, Mg2+ inhibits secretion and the IC50 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 Mg2+.
Larbi
K Y
KY
Department of Physiology, University College London, UK.
Gomperts
B D
BD
D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001192:Arylsulfatases / Q000378:metabolism; D001665:Binding Sites; D001667:Binding, Competitive; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000378:metabolism*; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism / Q000494:pharmacology; D006168:Guinea Pigs; D008274:Magnesium / Q000378:metabolism* / Q000494:pharmacology; D009195:Peroxidase / Q000378:metabolism; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
D016244:Guanosine 5'-O-(3-Thiotriphosphate); D000255:Adenosine Triphosphate; D009195:Peroxidase; D001192:Arylsulfatases; D001619:beta-N-Acetylhexosaminidases; D008274:Magnesium; D002118:Calcium