Release of Ca2+ from a nonmitochondrial intracellular store in pancreatic acinar cells by inositol-1,4,5-trisphosphate

Abstract

Activation of receptors for a wide variety of hormones and neurotransmitters leads to an increase in the intracellular level of calcium. Much of this calcium is released from intracellular stores but the link between surface receptors and this internal calcium reservoir is unknown. Hydrolysis of the phosphoinositides, which is another characteristic feature of these receptors^1–3, has been implicated in calcium mobilization¹. The primary lipid substrates for the receptor mechanism seem to be two polyphosphoinositides, phosphatidylinositol 4-phosphate (PtdIns4P) and phosphatidylinositol 4,5-bisphosphate (PtdIns4,5P₂), which are rapidly hydrolysed following receptor activation in various cells and tissues^4–10. The action of phospholipase C on these polyphosphoinositides results in the rapid formation of the water-soluble products inositol 1,4-bisphosphate (Ins1,4P₂) and inositol 1,4,5-trisphosphate (Ins1,4,5P₃)^9,11,12. In the insect salivary gland, where changes in Ins1,4P₂ and Ins1,4,5P₃ have been studied at early time periods, increases in these inositol phosphates are sufficiently rapid to suggest that they might mobilize internal calcium¹². We report here that micromolar concentrations of Ins1,4,5P₃ release Ca²⁺ from a nonmitochondrial intracellular Ca²⁺ store in pancreatic acinar cells. Our results strongly suggest that this is the same Ca²⁺ store that is released by acetylcholine.