title: Rapid regulation of a cyclic AMP-specific phosphodiesterase (PDE IV) by forskolin and isoproterenol in LRM55 astroglial cells.
abstract: Elevation of intracellular cyclic AMP (cAMP) levels by incubation of intact LRM55 astroglial cells with 0.1 mM forskolin or 0.1 microM isoproterenol (IPR) caused a rapid increase in soluble cAMP phospho-diesterase (PDE) activity. Activation did not require de novo protein synthesis and reached a maximum of > or = 100% increase over basal PDE activity after 15 min of treatment. The increase in activity was recovered in a single peak (peak 3) following DEAE chromatography; the other two peaks separated by this procedure showed no change. Peak 3 had all the characteristics of PDE IV: it was sensitive to rolipram, was insensitive to CI-930 and cyclic GMP (cGMP), had a high affinity for cAMP (K(m) approximately equal to 4 microM), and had a very low affinity for cGMP (K(m) > 100 microM). Forskolin treatment resulted in an increase of the Vmax of peak 3 without affecting its K(m). In vitro treatment of peak 3 with the catalytic subunit of protein kinase A increased activity, whereas treatment with alkaline phosphatase decreased activity. The rapid activation of this specific PDE in response to forskolin and IPR represents a novel regulation of PDE IV by a mechanism that seems to involve its phosphorylation by a cAMP-dependent protein kinase.
authors.affiliation: Laboratory of Neurotoxicology and Nervous System Disorders, Wadsworth Center for Laboratories and Research, New York State Department of Health, Albany 12201-0509, USA. madelian/wadsworth.org
authors.forename: V
authors.initials: V
authors.lastname: Madelian
authors.forename: E
authors.initials: E
authors.lastname: La Vigne
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000494:pharmacology*; D003513:Cycloheximide / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000187:drug effects*; D051381:Rats; D013997:Time Factors
chemical_list: D005576:Colforsin; D003513:Cycloheximide; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases; D007545:Isoproterenol