Role of phospholipase C and protein kinase C in vasoconstrictor-induced prostaglandin synthesis in cultured rat renal mesangial cells.
It was the aim of the present study to find out if a common mechanism exists by which the vasoconstrictive hormones angiotension II, noradrenaline and 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (AGEPC) increase prostaglandin E2 (PGE2) synthesis in cultures of rat renal mesangial cells. Angiotension II, noradrenaline and AGEPC stimulated PGE2 synthesis and uptake of 45Ca2+ in cultured mesangial cells. Both of these effects could be completely suppressed by the calcium channel blocker verapamil. Angiotensin II, noradrenaline and AGEPC caused a rapid breakdown of phosphatidylinositol 4,5-bisphosphate with a concomitant increase of 1,2-diacylglycerol and inositol trisphosphate, indicating an activation of phospholipase C by these hormones. Addition of verapamil had no effect on the hormone-induced stimulation of phospholipase C. The synthetic analogue of diacylglycerol, 1-oleoyl-2-acetylglycerol, and the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA), both of which are known to stimulate protein kinase C, enhanced PGE2 synthesis. Chelation of extracellular calcium with EDTA or addition of verapamil abolished the effect of 1-oleoyl-2-acetylglycerol and phorbol ester on PGE2 synthesis. 1-Oleoyl-2-acetylglycerol and phorbol ester increased the uptake of 45Ca2+ by the cells in a dose-dependent manner and this effect could be blocked by verapamil. The entirety of these data leads us to suggest that vasoconstrictor-evoked synthesis of PGE2 in rat mesangial cells is mediated by the subsequent activation of phospholipase C and protein kinase C. The activation of protein kinase C by diacylglycerol is likely to be involved in the increase of the calcium permeability of the plasma membrane which is a prerequisite for PGE2 synthesis induced by vasoconstrictive hormones.
Pfeilschifter
J
J
Kurtz
A
A
Bauer
C
C
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D015232:Dinoprostone; D004789:Enzyme Activation / Q000187:drug effects; D005920:Glomerular Mesangium / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D011458:Prostaglandins E / Q000096:biosynthesis*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D010738:Type C Phospholipases / Q000378:metabolism*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
D011458:Prostaglandins E; D014662:Vasoconstrictor Agents; D014700:Verapamil; D011493:Protein Kinase C; D010738:Type C Phospholipases; D015232:Dinoprostone; D002118:Calcium