Sphingosine-1-phosphate stimulates cortisol secretion.
We show here for the first time that sphingosine-1-phosphate (Sph-1-P) stimulates cortisol secretion in zona fasciculata cells of bovine adrenal glands. This effect was dependent upon protein kinase C (PKC) and extracellular Ca2+, and was inhibited by pertussis toxin. Sph-1-P activated phospholipase D (PLD) through a pertussis toxin-sensitive mechanism, also involving extracellular Ca2+ and PKC. Primary alcohols, which attenuate formation of phosphatidic acid (the product of PLD), and cell-permeable ceramides, which inhibit PLD, blocked Sph-1-P-induced cortisol secretion. In conclusion, Sph-1-P stimulates cortisol secretion through a mechanism involving Gi/o protein-coupled receptors, extracellular Ca2+, PKC and PLD.
Rábano
Miriam
M
Department of Biochemistry and Molecular Biology, Faculty of Sciences, University of the Basque Country, P.O. Box 644, 48080 Bilbao, Spain.
Peña
Ana
A
Brizuela
Leyre
L
Marino
Aida
A
Macarulla
José María
JM
Trueba
Miguel
M
Gómez-Muñoz
Antonio
A
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D002518:Ceramides / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism; D006854:Hydrocortisone / Q000378:metabolism*; D008055:Lipids / Q000494:pharmacology; D008246:Lysophospholipids; D037342:Pertussis Toxin / Q000494:pharmacology; D010712:Phosphatidic Acids / Q000096:biosynthesis; D010739:Phospholipase D / Q000037:antagonists & inhibitors / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D015383:Zona Fasciculata / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*
D002518:Ceramides; D002614:Chelating Agents; D008055:Lipids; D008246:Lysophospholipids; D010712:Phosphatidic Acids; C060506:sphingosine 1-phosphate; D037342:Pertussis Toxin; D011493:Protein Kinase C; D010739:Phospholipase D; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D020962:Heterotrimeric GTP-Binding Proteins; D013110:Sphingosine; D002118:Calcium; D006854:Hydrocortisone