title: The inhibitor of phospholipase-A2, AACOCF3, stimulates steroid secretion by dispersed human and rat adrenocortical cells.
abstract: AACOF3 is a trifluomethylketone analog of arachidonic acid, which inhibits phospholipase-A2 (PLA2). AACOCF3 was found to concentration-dependently increase basal aldosterone and corticosterone secretion by dispersed rat zona glomerulosa and zona fasciculata/reticularis cells, respectively, as well as aldosterone and cortisol production by dispersed human adrenocortical cells. Maximal effective concentration was 10(-5) M, and elicited about 2.5-3.0-fold rises in steroid output. 10(-5) M AACOCF3 also enhanced submaximally (10(-15)/10(-12) M), but not maximally (10(-9) M) ACTH-stimulated hormonal secretion. Quantitative HPLC showed that 10(-5) M AACOCF3 evokes similar increases (from 2.0- to 3.0-fold) in the basal release of the entire spectrum of adrenocortical steroids (i.e. both intermediate and definitive products of steroid synthesis), thereby suggesting that AACOCF3 acts on the early steps of steroid synthesis. Accordingly, when pregnenolone metabolism is prevented by cyanoketone, 10(-5) M AACOCF3 increased by about 8-10-fold the production of this steroid. In conclusion, we have demonstrated a side-effect of AACOCF3, which may become relevant in studies where this chemical is used to inhibit PLA2 in tissues able to convert cholesterol to pregnenolone.
authors.affiliation: Department of Anatomy, School of Medicine, University of Padua, Italy.
authors.forename: P G
authors.initials: PG
authors.lastname: Andreis
authors.forename: P
authors.initials: P
authors.lastname: Buttazzi
authors.forename: C
authors.initials: C
authors.lastname: Tortorella
authors.forename: R
authors.initials: R
authors.lastname: De Caro
authors.forename: F
authors.initials: F
authors.lastname: Aragona
authors.forename: G
authors.initials: G
authors.lastname: Neri
authors.forename: G G
authors.initials: GG
authors.lastname: Nussdorfer
mesh_terms: D000302:Adrenal Cortex / Q000187:drug effects / Q000502:physiology*; D000305:Adrenal Cortex Hormones / Q000096:biosynthesis*; D000450:Aldosterone / Q000378:metabolism*; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D002478:Cells, Cultured; D003345:Corticosterone / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D051381:Rats; D017207:Rats, Sprague-Dawley; D015383:Zona Fasciculata / Q000502:physiology; D015384:Zona Glomerulosa / Q000502:physiology; D015385:Zona Reticularis / Q000502:physiology
chemical_list: D000305:Adrenal Cortex Hormones; D001095:Arachidonic Acids; D004791:Enzyme Inhibitors; C081565:arachidonyltrifluoromethane; D000450:Aldosterone; D010741:Phospholipases A; D054467:Phospholipases A2; D003345:Corticosterone; D006854:Hydrocortisone