Effect of GTP and Ca2+ on inositol 1,4,5-trisphosphate induced Ca2+ release from permeabilized rat exocrine pancreatic acinar cells

Abstract The effects of Ca 2+ and GTP on the release of Ca 2+ from the inositol 1,4,5-trisphosphate (IP 3 ) sensitive Ca 2+ compartment were investigated with digitonin permeabilized rat pancreatic acinar cells. The amount of Ca 2+ released due to IP 3 directly correlated with the amount of stored Ca 2+ and was found to be inversely proportional to the medium free Ca 2+ concentration. Ca 2+ release induced by 0.18 μM IP 3 was half maximally inhibited at 0.5 μM free Ca 2+ , i.e. at concentrations observed in the cytosol of pancreatic acinar cells. GTP did not cause Ca 2+ release on its own, but a single addition of GTP (20 μM) abolished the apparent desensitization of the Ca 2+ release which was observed during repeated IP 3 applications. This effect of GTP was reversible. GTPγS could not replace GTP. Desensitization still occurred when GTPγS was added prior to GTP. The reported data indicate that GTP, stored Ca 2+ and cytosolic free Ca 2+ modulate the IP 3 induced Ca 2+ release.