PMID- 16822961 OWN - NLM STAT- MEDLINE DCOM- 20061212 LR - 20191210 IS - 0193-1849 (Print) IS - 0193-1849 (Linking) VI - 291 IP - 6 DP - 2006 Dec TI - An oxidized metabolite of linoleic acid increases intracellular calcium in rat adrenal glomerulosa cells. PG - E1160-7 AB - EKODE, an epoxy-keto derivative of linoleic acid, was previously shown to stimulate aldosterone secretion in rat adrenal glomerulosa cells. In the present study, we investigated the effect of exogenous EKODE on cytosolic [Ca(2+)] increase and aimed to elucidate the mechanism involved in this process. Through the use of the fluorescent Ca(2+)-sensitive dye Fluo-4, EKODE was shown to rapidly increase intracellular [Ca(2+)] ([Ca(2+)](i)) along a bell-shaped dose-response relationship with a maximum peak at 5 microM. Experiments performed in the presence or absence of Ca(2+) revealed that this increase in [Ca(2+)](i) originated exclusively from intracellular pools. EKODE-induced [Ca(2+)](i) increase was blunted by prior application of angiotensin II, Xestospongin C, and cyclopiazonic acid, indicating that inositol trisphosphate (InsP(3))-sensitive Ca(2+) stores can be mobilized by EKODE despite the absence of InsP(3) production. Accordingly, EKODE response was not sensitive to the phospholipase C inhibitor U-73122. EKODE mobilized a Ca(2+) 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 [Ca(2+)](i). 9-oxo-octadecadienoic acid, another oxidized derivative of linoleic acid, also increases [Ca(2+)](i), with a dose-response curve similar to EKODE. However, arachidonic and linoleic acids at 10 microM failed to increase [Ca(2+)](i) but did reduce the amplitude of the response to EKODE. It is concluded that EKODE mobilizes Ca(2+) from an InsP(3)-sensitive store and that this [Ca(2+)](i) increase is responsible for aldosterone secretion by glomerulosa cells. Similar bell-shaped dose-response curves for aldosterone and [Ca(2+)](i) increases reinforce this hypothesis. FAU - Payet, Marcel D AU - Payet MD AD - Department of Physiology, University of Sherbrooke, QC, Canada J1H 5N4. marcel.payet@usherbrooke.ca FAU - Goodfriend, Theodore L AU - Goodfriend TL FAU - Bilodeau, Lyne AU - Bilodeau L FAU - Mackendale, Cherilu AU - Mackendale C FAU - Chouinard, Lucie AU - Chouinard L FAU - Gallo-Payet, Nicole AU - Gallo-Payet N LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060705 PL - United States TA - Am J Physiol Endocrinol Metab JT - American journal of physiology. Endocrinology and metabolism JID - 100901226 RN - 0 (12,13-epoxy-9- keto-10-octadecenoic acid) RN - 0 (Fatty Acids) RN - 0 (Oleic Acids) RN - 0 (Steroids) RN - 11128-99-7 (Angiotensin II) RN - 132-06-9 (Inosine Triphosphate) RN - 4964P6T9RB (Aldosterone) RN - 9KJL21T0QJ (Linoleic Acid) RN - E0399OZS9N (Cyclic AMP) RN - EC 7.2.2.10 (Calcium-Transporting ATPases) RN - SY7Q814VUP (Calcium) SB - IM MH - Aldosterone/metabolism MH - Angiotensin II/pharmacology MH - Animals MH - Calcium/*metabolism MH - Calcium-Transporting ATPases/metabolism MH - Cyclic AMP/metabolism MH - Dose-Response Relationship, Drug MH - Fatty Acids/metabolism MH - In Vitro Techniques MH - Inosine Triphosphate/biosynthesis MH - Linoleic Acid/metabolism/*pharmacology MH - Oleic Acids/metabolism/*pharmacology MH - Oxidation-Reduction MH - Rats MH - Signal Transduction/drug effects MH - Steroids/biosynthesis MH - Zona Glomerulosa/cytology/drug effects/*metabolism EDAT- 2006/07/11 09:00 MHDA- 2006/12/13 09:00 CRDT- 2006/07/11 09:00 PHST- 2006/07/11 09:00 [pubmed] PHST- 2006/12/13 09:00 [medline] PHST- 2006/07/11 09:00 [entrez] AID - 00108.2006 [pii] AID - 10.1152/ajpendo.00108.2006 [doi] PST - ppublish SO - Am J Physiol Endocrinol Metab. 2006 Dec;291(6):E1160-7. doi: 10.1152/ajpendo.00108.2006. Epub 2006 Jul 5.