title: Involvement of phospholipase A2 in gentamicin-induced rat mesangial cell activation.
abstract: The role of the phospholipase A2 (PLA2) activation in the gentamicin (Gent)-induced rat mesangial cell activation has been studied. Gent (10(-5) M) induced a time-dependent mesangial planar cell surface area reduction that was significantly inhibited by the PLA2 inhibitors aristolochic acid (AA) and quinacrine, by the platelet-activating factor (PAF) blocker BN-52021 (BN), and by verapamil. These substances also inhibited Gent-induced [3H]thymidine incorporation into DNA (AA, 504 +/- 20; quinacrine, 555 +/- 66; BN, 1,126 +/- 120; and verapamil, 896 +/- 109; vs. 1,818 +/- 35 cpm/well in cells treated with Gent alone) and the Gent-induced increase in cell number (AA, 20,116 +/- 2,696; quinacrine, 24,687 +/- 1,481; BN, 26,122 +/- 1,016; and verapamil, 27,566 +/- 1,214; vs. 47,486 +/- 1,124 cells/well in cells treated with Gent alone). Gent induced a twofold increase in [3H]acetate incorporation into PAF (27 +/- 3 vs. 12 +/- 2 cpm/microgram protein in control conditions) that was completely blocked by AA, BN, or verapamil. Gent increased thromboxane B2 and prostaglandin E2 (PGE2) production, with both increases inhibited by either AA or verapamil. BN only inhibited the Gent-induced mesangial PGE2 production. In addition, Gent increased PLA2 activity (measured as [3H]arachiodonic acid release, 29,849 +/- 2,151 vs. 20,104 +/- 2,308 cpm/well in basal conditions), an effect that was blocked by AA (11,804 +/- 684 cpm/well). These data suggest a major role for PLA2 activation in Gent-induced mesangial cell contraction, proliferation and prostanoid secretion.
authors.affiliation: Departamento de Fisiología y Farmacología, Universidad de Salamanca, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Martínez-Salgado
authors.forename: A
authors.initials: A
authors.lastname: Rodríguez-Barbero
authors.forename: D
authors.initials: D
authors.lastname: Rodríguez-Puyol
authors.forename: G
authors.initials: G
authors.lastname: Pérez de Lema
authors.forename: J M
authors.initials: JM
authors.lastname: López-Novoa
mesh_terms: D000085:Acetates / Q000378:metabolism; D000818:Animals; D034341:Aristolochic Acids; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D015232:Dinoprostone / Q000378:metabolism; D004224:Diterpenes; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005839:Gentamicins / Q000494:pharmacology*; D046934:Ginkgolides; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D007783:Lactones / Q000494:pharmacology; D010616:Phenanthrenes / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054467:Phospholipases A2; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D011796:Quinacrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013936:Thymidine / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology
chemical_list: D000085:Acetates; D034341:Aristolochic Acids; D004224:Diterpenes; D004791:Enzyme Inhibitors; D005839:Gentamicins; D046934:Ginkgolides; D007783:Lactones; D010616:Phenanthrenes; D010972:Platelet Activating Factor; D004247:DNA; C000228:aristolochic acid I; D014700:Verapamil; C045856:ginkgolide B; D010741:Phospholipases A; D054467:Phospholipases A2; D011796:Quinacrine; D015232:Dinoprostone; D013936:Thymidine