Angiotensin II-stimulated cortisol secretion is mediated by phospholipase D.
Angiotensin II (Ang-II) regulates a variety of cellular functions including cortisol secretion. In the present report, we demonstrate that Ang-II activates phospholipase D (PLD) in zona fasciculata (ZF) cells of bovine adrenal glands, and that this effect is associated to the stimulation of cortisol secretion by this hormone. PLD activation was dependent upon extracellular Ca2+, and was blocked by inhibition of protein kinase C (PKC). Using the reverse transcription-polymerase chain reaction technique, we demonstrated that ZF cells express both PLD-1 and PLD-2 isozymes. Primary alcohols, which attenuate the formation of phosphatidate (the product of PLD), and cell-permeable ceramides, which inhibit PLD potently, blocked Ang-II-stimulated cortisol secretion. Furthermore, propranolol or chlorpromazine, which are potent inhibitors of phosphatidate phosphohydrolase (PAP) (the enzyme that produces diacylglycerol from phosphatidate), also blocked cortisol secretion. These data suggest that the PLD/PAP pathway plays an important role in the regulation of cortisol secretion by Ang-II in ZF cells.
Rábano
Miriam
M
Department of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country, P.O. Box 644, 48080 Bilbao, Spain.
Peña
Ana
A
Brizuela
Leyre
L
Macarulla
José María
JM
Gómez-Muñoz
Antonio
A
Trueba
Miguel
M
D000311:Adrenal Glands / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D002518:Ceramides / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006854:Hydrocortisone / Q000378:metabolism*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D010711:Phosphatidate Phosphatase / Q000037:antagonists & inhibitors; D010739:Phospholipase D / Q000235:genetics / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D015383:Zona Fasciculata / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology
D002518:Ceramides; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D012333:RNA, Messenger; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D011493:Protein Kinase C; D010711:Phosphatidate Phosphatase; C105606:phospholipase D2; D010739:Phospholipase D; C106801:phospholipase D1; D002118:Calcium; D006854:Hydrocortisone