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Arachidonic acid is a physiological activator of the ryanodine receptor in pancreatic beta-cells.
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2006 (English)In: Cell Calcium, ISSN 0143-4160, E-ISSN 1532-1991, Vol. 39, no 6, 529-37 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2006. Vol. 39, no 6, 529-37 p.
URN: urn:nbn:se:uu:diva-132138DOI: 10.1016/j.ceca.2006.02.003PubMedID: 16620964OAI: oai:DiVA.org:uu-132138DiVA: diva2:357051
Available from: 2010-10-15 Created: 2010-10-15 Last updated: 2010-10-15

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