The regulation of cytosolic Ca 2؉ is important for a variety of cell functions. One non-inositol 1,4,5-trisphosphate (IP 3 ) compound that may regulate Ca 2؉ is palmitoyl-coenzyme A (CoA), a fatty acid-CoA that is reported to cause Ca 2؉ release from intracellular stores of oocytes, myocytes, and hepatocytes. To study the role of palmitoyl-CoA in the pancreatic acinar cell, rat pancreatic acini were isolated by collagenase digestion, permeablized with streptolysin O, and the release of Ca 2؉

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... m internal stores was measured with fura-2. Palmitoyl-CoA released Ca 2؉ from internal stores (EC 50 ‫؍‬ 14 M). The palmitoyl-CoA-sensitive pool was distinct from, and overlapping with the IP 3 -sensitive Ca 2؉ pool. The effects of submaximal doses of IP 3 or cyclic ADP-ribose plus palmitoyl-CoA were additive. Fatty acid-CoA derivatives with carbon chain lengths of 16 -18 were the most potent and efficacious. Ryanodine and caffeine or elevated resting [Ca 2؉ ] sensitized the Ca 2؉ pool to the actions of palmitoyl-CoA. Fatty acid-CoA levels in pancreatic acini were measured by extraction with 2-propanol/ acetonitrile, followed by separation and quantification using reverse phase high performance liquid chromatography, and were found to be 10.17 ؎ 0.93 nmol/mg protein. These data suggest the presence of an IP 3 -insensitive palmitoyl-CoA-sensitive Ca 2؉ store in pancreatic acinar cells and suggest that palmitoyl-CoA may be needed for Ca 2؉ -induced Ca 2؉ release.