Alpha 1-adrenergic receptor-mediated phosphoinositide hydrolysis and prostaglandin E2 formation in Madin-Darby canine kidney cells. Possible parallel activation of phospholipase C and phospholipase A2.
alpha 1-Adrenergic receptors mediate two effects on phospholipid metabolism in Madin-Darby canine kidney (MDCK-D1) cells: hydrolysis of phosphoinositides and arachidonic acid release with generation of prostaglandin E2 (PGE2). The similarity in concentration dependence for the agonist (-)-epinephrine in eliciting these two responses implies that they are mediated by a single population of alpha 1-adrenergic receptors. However, we find that the kinetics of the two responses are quite different, PGE2 production occurring more rapidly and transiently than the hydrolysis of phosphoinositides. The antibiotic neomycin selectively decreases alpha 1-receptor-mediated phosphatidylinositol 4,5-bisphosphate hydrolysis without decreasing alpha 1-receptor-mediated arachidonic acid release and PGE2 generation. In addition, receptor-mediated inositol trisphosphate formation is independent of extracellular calcium, whereas release of labeled arachidonic acid is largely calcium-dependent. Moreover, based on studies obtained with labeled arachidonic acid, receptor-mediated generation of arachidonic acid cannot be accounted for by breakdown of phosphatidylinositol monophosphate, phosphatidylinositol bisphosphate, or phosphatidic acid. Further studies indicate that epinephrine produces changes in formation or turnover of several classes of membrane phospholipids in MDCK cells. We conclude that alpha 1-adrenergic receptors in MDCK cells appear to regulate phospholipid metabolism by the parallel activation of phospholipase C and phospholipase A2. This parallel activation of phospholipases contrasts with models described in other systems which imply sequential activation of phospholipase C and diacylglycerol lipase or phospholipase A2.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology; D002460:Cell Line; D015232:Dinoprostone; D004285:Dogs; D004789:Enzyme Activation; D004837:Epinephrine / Q000494:pharmacology; D006868:Hydrolysis; D007668:Kidney / Q000378:metabolism*; D007700:Kinetics; D009355:Neomycin / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D010740:Phospholipases / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D010761:Phosphorus Radioisotopes; D011458:Prostaglandins E / Q000096:biosynthesis*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D010738:Type C Phospholipases / Q000378:metabolism*
D001095:Arachidonic Acids; D010716:Phosphatidylinositols; D010761:Phosphorus Radioisotopes; D011458:Prostaglandins E; D011942:Receptors, Adrenergic, alpha; D016718:Arachidonic Acid; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases; D009355:Neomycin; D015232:Dinoprostone; D002118:Calcium; D004837:Epinephrine