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, has been implicated in calcium mobilization. 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. 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). In the insect salivary gland, where changes in Ins1,4P2 and Ins1,4,5P2 have been studied at early time periods, increases in these inositol phosphates are sufficiently rapid to suggest that they might mobilize internal calcium. 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.

Polyphosphoinositide hydrolysis by phospholipase C is accelerated by thyrotropin releasing hormone (TRH) in clonal rat pituitary cells (GH3 cells)

“…It has been shown very recently in pancreatic acinar cells that Ins(1,4,5)P3 can release Ca2+ from a nonmitochondrial intracellular pool [26]; the rise in Ins(l,4,5)P3 following TRH stimulation of PtdIns(4,5)P2 hydrolysis could thus provide the link between the phospholipid response and the mobilization of intracellular Ca" [2,3].…”

“…PA, increased in steady state in the presence of TRH [8], is a Ca2+ ionophore [29] and a main source for the precursor arachidonic acid utilized in prostaglandin and leukotriene synthesis [30,31]. Both protein kinase C and arachidonic acid metabolism are also regulated by Ca2+ [25,26,29] such that [Ca2'], could modulate these processes in the stimulated cells. It seems therefore that the correlation of Ca2+ mobilization with the phospholipid response [9,12] also reflects coordinate control of cellular responses.…”

Emerging roles of inositol 1,4,5-trisphosphate signaling in cardiac myocytes

“…A quarter of a century ago it was shown that D-myo inositol 1,4,5-trisphosphate (IP 3 ) releases Ca 2+ from a non-mitochondrial internal Ca 2+ store [1]. Since this hallmark discovery, IP 3 has emerged as a ubiquitous intracellular messenger, releasing Ca 2+ from stores through activation of IP 3 receptors (IP 3 Rs) in almost all eukaryotic cells.…”

Decavanadate displaces inositol 1,4,5-trisphosphate (IP3) from its receptor and inhibits IP3 induced Ca2+ release in permeabilized pancreatic acinar cells

“…Labelled IP3 was displaced from these subcellular membranes with similar kinetics by unlabelled IP3 and decavanadate. The data suggest that the inhibitory action of decavanadate on IP3 induced Ca 2 + release is a consequence of its effect on binding of IP3 to its receptor.Intracellular inositol 1,4,5-trisphosphate (IP3), latter was shown for the fIrst time with fOImed at the plasma membrane by the hydrolysis of pelTIleabilized rat pancreatic acinar cells [2] and was phosphatidylinositol-4,5-bisphosphate, causes the subsequently confltmed by innumerable release of Ca 2 + from intracellular stores [1]. The investigations in a variety of cells.…”

“…Intracellular inositol 1,4,5-trisphosphate (IP3), latter was shown for the fIrst time with fOImed at the plasma membrane by the hydrolysis of pelTIleabilized rat pancreatic acinar cells [2] and was phosphatidylinositol-4,5-bisphosphate, causes the subsequently confltmed by innumerable release of Ca 2 + from intracellular stores [1]. The investigations in a variety of cells.…”