title: Acyl-coenzyme A causes Ca2+ release in pancreatic acinar cells.
abstract: The regulation of cytosolic Ca2+ is important for a variety of cell functions. 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, 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 Ca2+ from internal stores was measured with fura-2. Palmitoyl-CoA released Ca2+ from internal stores (EC50 = 14 microM). The palmitoyl-CoA-sensitive pool was distinct from, and overlapping with the IP3-sensitive Ca2+ pool. The effects of submaximal doses of IP3 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 [Ca2+] sensitized the Ca2+ 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 IP3-insensitive palmitoyl-CoA-sensitive Ca2+ store in pancreatic acinar cells and suggest that palmitoyl-CoA may be needed for Ca2+-induced Ca2+ release.
authors.affiliation: Department of Veterans Affairs Medical Center, West Los Angeles, California, USA. pancreas@ucla.edu
authors.forename: T J
authors.initials: TJ
authors.lastname: Fitzsimmons
authors.forename: J A
authors.initials: JA
authors.lastname: McRoberts
authors.forename: K H
authors.initials: KH
authors.lastname: Tachiki
authors.forename: S J
authors.initials: SJ
authors.lastname: Pandol
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism*; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D010171:Palmitoyl Coenzyme A / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D010179:Pancreas / Q000378:metabolism*; D051381:Rats; D012433:Ryanodine / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D000214:Acyl Coenzyme A; D004791:Enzyme Inhibitors; D019837:Ryanodine Receptor Calcium Release Channel; D012433:Ryanodine; D010171:Palmitoyl Coenzyme A; D002110:Caffeine; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D000252:Calcium-Transporting ATPases; D002118:Calcium