Regulation of isoproterenol-induced cyclic AMP accumulation in LRM55 glial cells by phosphodiesterase.
Continuous stimulation of LRM55 glial cells with the beta adrenergic agonist isoproterenol (IRP) produced a transient increase in intracellular cyclic AMP (cAMP). Pretreatment of cells for 1, 5 and 30 min with IPR followed by a 1-min challenge with IPR resulted in 20, 50 and 70% drops in maximum stimulation, respectively, with no significant change in the EC50 value (60 nM). Cells stimulated with IRP in the presence of the phosphodiesterase inhibitor RO 20-1724 reached intracellular cAMP levels 6 to 8 times higher than controls and maintained these levels for at least 60 min of continuous stimulation. Addition of RO 20-1724 to cells showing a reduced response after exposure to IPR resulted in an immediate and sustained increase of cAMP levels. Because RO 20-1724 nearly completely inhibited cAMP degradation, the authors conclude that the apparent inactivation of IPR-stimulated cAMP response in the LMR55 cells is due mainly to cAMP degradation by phosphodiesterase activity.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology*; D009457:Neuroglia / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000502:physiology*
D010726:Phosphodiesterase Inhibitors; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases; D007545:Isoproterenol; D015056:1-Methyl-3-isobutylxanthine