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Am J Physiol Endocrinol Metab 291: E1160-E1167, 2006. First published July 5, 2006; doi:10.1152/ajpendo.00108.2006
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An oxidized metabolite of linoleic acid increases intracellular calcium in rat adrenal glomerulosa cells

Marcel D. Payet,1 Theodore L. Goodfriend,3 Lyne Bilodeau,1 Cherilu Mackendale,1 Lucie Chouinard,1 and Nicole Gallo-Payet1,2

1Department of Physiology and Biophysics and 2Service of Endocrinology, Department of Medicine, Faculty of Medicine, University of Sherbrooke, Sherbrooke, Quebec, Canada; and 3William S. Middleton Memorial Veterans Hospital and Departments of Medicine and Pharmacology, University of Wisconsin, Madison, Wisconsin

Submitted 8 March 2006 ; accepted in final form 27 June 2006

EKODE, an epoxy-keto derivative of linoleic acid, was previously shown to stimulate aldosterone secretion in rat adrenal glomerulosa cells (15). In the present study, we investigated the effect of exogenous EKODE on cytosolic [Ca2+] increase and aimed to elucidate the mechanism involved in this process. Through the use of the fluorescent Ca2+-sensitive dye Fluo-4, EKODE was shown to rapidly increase intracellular [Ca2+] ([Ca2+]i) along a bell-shaped dose-response relationship with a maximum peak at 5 µM. Experiments performed in the presence or absence of Ca2+ revealed that this increase in [Ca2+]i originated exclusively from intracellular pools. EKODE-induced [Ca2+]i increase was blunted by prior application of angiotensin II, Xestospongin C, and cyclopiazonic acid, indicating that inositol trisphosphate (InsP3)-sensitive Ca2+ stores can be mobilized by EKODE despite the absence of InsP3 production. Accordingly, EKODE response was not sensitive to the phospholipase C inhibitor U-73122. EKODE mobilized a Ca2+ store included in the thapsigargin (TG)-sensitive stores, although the interaction between EKODE and TG appears complex, since EKODE added at the plateau response of TG induced a rapid drop in [Ca2+]i. 9-Oxo-octadecadienoic acid, another oxidized derivative of linoleic acid, also increases [Ca2+]i, with a dose-response curve similar to EKODE. However, arachidonic and linoleic acids at 10 µM failed to increase [Ca2+]i but did reduce the amplitude of the response to EKODE. It is concluded that EKODE mobilizes Ca2+ from an InsP3-sensitive store and that this [Ca2+]i increase is responsible for aldosterone secretion by glomerulosa cells. Similar bell-shaped dose-response curves for aldosterone and [Ca2+]i increases reinforce this hypothesis.

intracellular calcium ion concentration



Address for reprint requests and other correspondence: M. D. Payet, Département de physiologie et biophysioque, Faculté de médecine, Université de Sherbrooke, 3001–12èmeAvenue Nord, Sherbrooke, QC, Canada J1H 5N4 (e-mail: marcel.payet{at}usherbrooke.ca)







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