Arachidonic acid is a physiological activator of the ryanodine receptor in pancreatic beta-cells.
Pancreatic beta-cells have ryanodine receptors but little is known about their physiological regulation. Previous studies have shown that arachidonic acid releases Ca(2+) from intracellular stores in beta-cells but the identity of the channels involved in the Ca(2+) release has not been elucidated. We studied the mechanism by which arachidonic acid induces Ca(2+) concentration changes in pancreatic beta-cells. Cytosolic free Ca(2+) concentration was measured in fura-2-loaded INS-1E cells and in primary beta-cells from Wistar rats. The increase of cytosolic Ca(2+) concentration induced by arachidonic acid (150microM) was due to both Ca(2+) release from intracellular stores and influx of Ca(2+) from extracellular medium. 5,8,11,14-Eicosatetraynoic acid, a non-metabolizable analogue of arachidonic acid, mimicked the effect of arachidonic acid, indicating that arachidonic acid itself mediated Ca(2+) increase. The Ca(2+) release induced by arachidonic acid was from the endoplasmic reticulum since it was blocked by thapsigargin. 2-Aminoethyl diphenylborinate (50microM), which is known to inhibit 1,4,5-inositol-triphosphate-receptors, did not block Ca(2+) release by arachidonic acid. However, ryanodine (100microM), a blocker of ryanodine receptors, abolished the effect of arachidonic acid on Ca(2+) release in both types of cells. These observations indicate that arachidonic acid is a physiological activator of ryanodine receptors in beta-cells.
Woolcott
Orison O
OO
Karolinska Institutet, Södersjukhuset, Department of Internal Medicine, Research Center, SE-118 83 Stockholm, Sweden. Orison.Woolcott@sos.ki.se
Gustafsson
Amanda J
AJ
Dzabic
Mensur
M
Pierro
Cristina
C
Tedeschi
Patrizia
P
Sandgren
Johanna
J
Bari
M Rizuanul
MR
Nguyen
K Hoa
KH
Bianchi
Marta
M
Rakonjac
Marija
M
Rådmark
Olof
O
Ostenson
Claes-Göran
CG
Islam
Md Shahidul
MS
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000378:metabolism; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D009553:Nimodipine / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*
D020746:Calcium Channels, L-Type; D053496:Inositol 1,4,5-Trisphosphate Receptors; D019837:Ryanodine Receptor Calcium Release Channel; D016718:Arachidonic Acid; D009569:Nitric Oxide; D009553:Nimodipine