Arachidonic acid is a physiological activator of the ryanodine receptor in pancreatic β-cells

Pancreatic β-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 β-cells but the identity of the channels involved in the Ca 2+ release has not been elucidated. We studi...

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Veröffentlicht in:Cell calcium (Edinburgh) 2006-06, Vol.39 (6), p.529-537
Hauptverfasser: Woolcott, Orison O., Gustafsson, Amanda J., Dzabic, Mensur, Pierro, Cristina, Tedeschi, Patrizia, Sandgren, Johanna, Bari, M. Rizuanul, Hoa, Nguyen K., Bianchi, Marta, Rakonjac, Marija, Rådmark, Olof, Östenson, Claes-Göran, Islam, Md. Shahidul
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container_end_page 537
container_issue 6
container_start_page 529
container_title Cell calcium (Edinburgh)
container_volume 39
creator Woolcott, Orison O.
Gustafsson, Amanda J.
Dzabic, Mensur
Pierro, Cristina
Tedeschi, Patrizia
Sandgren, Johanna
Bari, M. Rizuanul
Hoa, Nguyen K.
Bianchi, Marta
Rakonjac, Marija
Rådmark, Olof
Östenson, Claes-Göran
Islam, Md. Shahidul
description Pancreatic β-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 β-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 β-cells. Cytosolic free Ca 2+ concentration was measured in fura-2-loaded INS-1E cells and in primary β-cells from Wistar rats. The increase of cytosolic Ca 2+ concentration induced by arachidonic acid (150 μM) 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 (50 μM), which is known to inhibit 1,4,5-inositol-triphosphate-receptors, did not block Ca 2+ release by arachidonic acid. However, ryanodine (100 μM), 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 β-cells.
doi_str_mv 10.1016/j.ceca.2006.02.003
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subjects Animals
Arachidonic acid
Arachidonic Acid - pharmacology
Calcium channels
Calcium Channels, L-Type - metabolism
Calcium Signaling - drug effects
Calcium signalling
Cells, Cultured
Endoplasmic Reticulum - secretion
Inositol 1,4,5-Trisphosphate Receptors - metabolism
Insulin-Secreting Cells - drug effects
Insulin-Secreting Cells - metabolism
Male
Nimodipine - pharmacology
Nitric Oxide - metabolism
Pancreatic β-cells
Rats
Rats, Wistar
Ryanodine Receptor Calcium Release Channel - metabolism
Ryanodine receptors
title Arachidonic acid is a physiological activator of the ryanodine receptor in pancreatic β-cells
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