Regulation of isoproterenol-induced cyclic AMP accumulation in LRM55 glial cells by phosphodiesterase
Madelian, V.; Shain, W.
Journal of Pharmacology and Experimental Therapeutics 243(2): 618-623
1987
ISSN/ISBN: 0022-3565 PMID: 2445955 Document Number: 286238
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.