ACYL-COENZYME-A CAUSES CA2-CELLS( RELEASE IN PANCREATIC ACINAR)

The regulation of cytosolic Ca2+ is important for a variety of cell fu nctions. One non-inositol 1,4,5-trisphosphate (IP3) compound that may regulate Ca2+ is palmitoyl-coenzyme A (CoA), a fatty acid-CoA that is reported to cause Ca2+ release from intracellular stores of oocytes, m yocytes, and hepatocytes. To study the role of palmitoyl-CoA in the pa ncreatic acinar cell, rat pancreatic acini were isolated by collagenas e digestion, permeablized with streptolysin O, and the release of Ca2 from internal stores was measured with fura-2. Palmitoyl-CoA released Ca2+ from internal stores (EC50 = 14 mu M). The palmitoyl-CoA-sensiti ve pool was distinct from, and overlapping with the IP3-sensitive Ca2 pool. The effects of submaximal doses of IP3 or cyclic ADP-ribose plu s 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 [Ca2+] sensitized the Ca2+ pool to t he 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 li quid chromatography, and were found to be 10.17 +/- 0.93 nmol/mg prote in. These data suggest the presence of an IP3-insensitive palmitoyl-Co A-sensitive Ca2+ store in pancreatic acinar cells and suggest that pal mitoyl-CoA may be needed for Ca2+-induced Ca2+ release.