Phorbol ester inhibits arginine vasopressin activation of phospholipase C and promotes contraction of, and prostaglandin production by, cultured mesangial cells.
We have previously shown that arginine vasopressin (AVP) causes a rapid (5-10 min) contractile response in cultured mesangial cells plated onto slippery substrata such as poly(hydroxyethyl methacrylate)-coated dishes. This contraction is associated with an increase in the levels of inositol trisphosphate (InsP3), diacylglycerol and prostaglandin E2 (PGE2). We now report that agents which are known to activate protein kinase C, i.e. phorbol 12-myristate 13-acetate (PMA) and oleolylacetylglycerol (OAG), also contract mesangial cells; however, the contractile response is slow to develop (15-30 min). The inactive phorbol ester, 4 alpha -phorbol 12,13-didecanoate, did not elicit contraction. PMA and OAG did not increase InsP3 release in mesangial cells. However, pretreatment of mesangial cells with PMA inhibited the formation of InsP3. This inhibition could not be explained by a reduction in AVP binding since PMA treatment did not influence the number or affinity of [3H]AVP binding sites in intact cells. PMA alone stimulated PGE2 production in mesangial cells to a degree similar to AVP. Contrary to what was seen with InsP3, pretreatment of cells with PMA before AVP had an additive effect on arachidonic acid release and PGE2 production. Thus, there is an apparent dissociation of phospholipase C activity from that of phospholipase A2.
D001127:Arginine Vasopressin / Q000037:antagonists & inhibitors*; D002478:Cells, Cultured; D015232:Dinoprostone; D004789:Enzyme Activation / Q000187:drug effects; D005227:Fatty Acids / Q000378:metabolism; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000378:metabolism; D008858:Microscopy, Phase-Contrast; D010703:Phorbol Esters / Q000494:pharmacology*; D011458:Prostaglandins E / Q000096:biosynthesis*; D010738:Type C Phospholipases / Q000378:metabolism*
D005227:Fatty Acids; D007295:Inositol Phosphates; D010703:Phorbol Esters; D011458:Prostaglandins E; D001127:Arginine Vasopressin; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases; D015232:Dinoprostone