title: Arachidonic acid mobilizes Ca2+ from the endoplasmic reticulum and an acidic store in rat pancreatic β cells.
abstract: In rat pancreatic β cells, arachidonic acid (AA) triggered intracellular Ca(2+) release. This effect could be mimicked by eicosatetraynoic acid, indicating that AA metabolism is not required. The AA-mediated Ca(2+) signal was not affected by inhibition of ryanodine receptors or emptying of ryanodine-sensitive store but was reduced by ∼70% following the disruption of acidic stores (treatment with bafilomycin A1 or glycyl-phenylalanyl-β-naphthylamide (GPN)). The action of AA did not involve TRPM2 channels or NAADP receptors because intracellular dialysis of adenosine diphosphoribose (ADPR; an activator of TRPM2 channels) or NAADP did not affect the AA response. In contrast, stimulation of IP(3) receptors via intracellular dialysis of adenophostin A, or exogenous application of ATP largely abolished the AA-mediated Ca(2+) signal. Intracellular dialysis of heparin abolished the ATP-mediated Ca(2+) signal but not the AA response, suggesting that the action of AA did not involve the IP(3)-binding site. Treatment with the SERCA pump inhibitor, thapsigargin, reduced the amplitude of the AA-mediated Ca(2+) signal by ∼70%. Overall, our finding suggests that AA mobilizes Ca(2+) from the endoplasmic reticulum as well as an acidic store and both stores could be depleted by IP(3) receptor agonist. The possibility of secretory granules as targets of AA is discussed.
authors.affiliation: Centre for Neuroscience, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Valerie
authors.initials: V
authors.lastname: Yeung-Yam-Wah
authors.forename: Andy K
authors.initials: AK
authors.lastname: Lee
authors.forename: Amy
authors.initials: A
authors.lastname: Tse
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism*; D018942:Macrolides / Q000494:pharmacology; D008297:Male; D009249:NADP / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D022142:Secretory Vesicles / Q000378:metabolism; D050053:TRPM Cation Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D002120:Calcium Channel Agonists; D004791:Enzyme Inhibitors; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018942:Macrolides; D050053:TRPM Cation Channels; C557080:Trpm2 protein, rat; C085029:adenophostin A; D016718:Arachidonic Acid; D009249:NADP; C024376:NAADP; D019284:Thapsigargin; C040929:bafilomycin A1; D000255:Adenosine Triphosphate; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000241:Adenosine; D002118:Calcium