title: A role for phospholipase D in angiotensin II-induced protein kinase D activation in adrenal glomerulosa cell models.
abstract: The mineralocorticoid aldosterone plays an important role in regulating blood pressure, with excess causing hypertension and exacerbating cardiovascular disease. Previous studies have indicated a role for both phospholipase D (PLD) and protein kinase D (PKD) in angiotensin II (AngII)-regulated aldosterone production in adrenal glomerulosa cells. Therefore, the relationship between AngII-activated PLD and PKD was determined in two glomerulosa cell models, primary bovine zona glomerulosa (ZG) and HAC15 human adrenocortical carcinoma cells, using two inhibitors, 1-butanol and the reported PLD inhibitor, fluoro-2-indolyl des-chlorohalopemide (FIPI). FIPI was first confirmed to decrease PLD activation in response to AngII in the two glomerulosa cell models. Subsequently, it was shown that both 1-butanol and FIPI inhibited AngII-elicited PKD activation and aldosterone production. These results indicate that PKD is downstream of PLD and suggest that PKD is one of the mechanisms through which PLD promotes aldosterone production in response to AngII in adrenal glomerulosa cells.
authors.affiliation: Department of Physiology, Georgia Health Sciences University (formerly the Medical College of Georgia), 1120 15th Street, Augusta, GA 30912, United States.
authors.forename: Lawrence O
authors.initials: LO
authors.lastname: Olala
authors.forename: Mutsa
authors.initials: M
authors.lastname: Seremwe
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Tsai
authors.forename: Wendy B
authors.initials: WB
authors.lastname: Bollag
mesh_terms: D020001:1-Butanol; D000450:Aldosterone / Q000096:biosynthesis; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004294:Domperidone / Q000031:analogs & derivatives / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D006888:Hydroxycholesterols / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology; D008954:Models, Biological; D010739:Phospholipase D / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D015384:Zona Glomerulosa / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology
chemical_list: C546435:5-fluoro-2-indolyldeschlorohalopemide; D004791:Enzyme Inhibitors; D006888:Hydroxycholesterols; D007211:Indoles; D000804:Angiotensin II; C003585:22-hydroxycholesterol; D000450:Aldosterone; D004294:Domperidone; D020001:1-Butanol; C089212:protein kinase D; D011493:Protein Kinase C; D010739:Phospholipase D