Stimulation of cytosolic free calcium and inositol phosphates by prostaglandins in cultured rat mesangial cells.
We studied the effects of four products of arachidonate cyclo-oxygenation on a phospholipase C-dependent signal transduction system in cultured rat glomerular mesangial cells. PGF2 alpha, PGE2 and the thromboxane A2/endoperoxide analogue U-46619 rapidly increased cytosolic free Ca2+, measured in monolayers loaded with the fluorescent intracellular probe fura-2. Peak responses were dose-dependent and unaffected by chelation of extracellular Ca2+, indicating release from internal stores. The thromboxane A2-receptor antagonist SQ 27,427 selectively inhibited responses to U-46619. The PGI2 analogue Iloprost had no effect on cytosolic Ca2+. PGF2 alpha, PGE2 and U-46619 also stimulated accumulation of total inositol phosphates during 15 min incubations. We conclude that phospholipase C activation mediates the effects of certain eicosanoids on the glomerular mesangium.
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005920:Glomerular Mesangium / Q000187:drug effects* / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology*; D051381:Rats; D013403:Sugar Phosphates / Q000378:metabolism*; D010738:Type C Phospholipases / Q000032:analysis
D007295:Inositol Phosphates; D011450:Prostaglandin Endoperoxides, Synthetic; D011453:Prostaglandins; D013403:Sugar Phosphates; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D010738:Type C Phospholipases; D002118:Calcium