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A more recent version of this article appeared on June 1, 2006

Papers In Press, published online ahead of print March 22, 2006
J. Lipid Res., doi:10.1194/jlr.M500510-JLR200
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Submitted on November 22, 2005
Revised on March 16, 2006
Accepted on March 21, 2006

Sphingosine 1-phosphate: a new stimulator of aldosterone secretion

Leyre Brizuela, Miriam Rábano, Ana Peña, Patricia Gangoiti, José María Macarulla, Miguel Trueba, and Antonio Gómez-Muñoz

Biochemistry and Molecular Biology, University of the Basque Country, Bilbao, Bizkaia 48080

Corresponding Author: antonio.gomez{at}ehu.es

Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid capable of regulating critical physiological and pathological functions. Here, we report for the first time that S1P stimulates aldosterone secretion in cells of the zona glomerulosa of the adrenal gland. Regulation of aldosterone secretion is important because this hormone controls electrolyte and fluid balance, and is implicated in cardiovascular homeostasis. S1P-stimulated aldosterone secretion was dependent upon the protein kinase C (PKC) isoforms alpha and delta , and extracellular Ca{2+}, and it was inhibited by pertussis toxin. S1P activated phospholipase D (PLD) through a pertussis toxin-sensitive mechanism, also involving PKCalpha and delta , and extracellular Ca{2+}. Primary alcohols, which attenuate the formation of phosphatidic acid (the product of PLD), and cell-permeable ceramides, which inhibit PLD activity, blocked S1P-stimulated aldosterone secretion. Furthermore, propranolol, chlorpromazine, or sphingosine, which are potent inhibitors of phosphatidate phosphohydrolase (PAP) (the enzyme that produces diacylglycerol from phosphatidate), also blocked aldosterone secretion. These data suggest that the PLD/PAP pathway plays a crucial role in the regulation of aldosterone secretion by S1P, and that Gi protein-coupled receptors, extracellular Ca{2+}, and the PKC isoforms alpha and delta are all important components in the cascade of events controlling this process.


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L. Brizuela, M. Rabano, P. Gangoiti, N. Narbona, J. M. Macarulla, M. Trueba, and A. Gomez-Munoz
Sphingosine-1-phosphate stimulates aldosterone secretion through a mechanism involving the PI3K/PKB and MEK/ERK 1/2 pathways
J. Lipid Res., October 1, 2007; 48(10): 2264 - 2274.
[Abstract] [Full Text] [PDF]


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