title: Naproxen inhibits hepatic glycogenolysis induced by Ca(2+)-dependent agents.
abstract: 1. The non-steroidal anti-inflammatory naproxen inhibited steady-state glycogenolysis stimulation caused by norepinephrine, phenylephrine (alpha 1-agonists) and methotrexate (not receptor mediated) in the isolated perfused rat liver. Stimulation of glycogenolysis caused by these agents is Ca(2+)-dependent. 2. Naproxen did not inhibit glycogenolysis stimulation caused by glucagon. 3. The action of naproxen depended on the extracellular Ca2+ concentration. At 0.25 mM extracellular Ca2+, the norepinephrine stimulated glycogenolysis was inhibited by 60% by 0.5 mM naproxen. At 3.5 mM Ca2+, inhibition was reduced to 25%. The inhibition degree correlated linearly with the extracellular Ca2+ concentration. 4. 45Ca2+ efflux stimulation caused by norepinephrine was not affected by naproxen, indicating that the mobilization of the intracellular Ca2+ pools was not significantly affected by naproxen. The initial increases in glycogenolysis caused by norepinephrine in the absence of extracellular Ca2+ (pre steady-state) were not affected by naproxen. These increases depend on intracellular Ca2+ mobilization. 5. It can be concluded that the action of naproxen is most probably related to the cytosolic Ca2+ concentration which, under steady-state conditions, depends on the extracellular one during the action of Ca(2+)-dependent glycogenolytic agents.
authors.affiliation: Department of Biochemistry, University of Maringá, Brazil.
authors.forename: E A
authors.initials: EA
authors.lastname: Nascimento
authors.forename: N S
authors.initials: NS
authors.lastname: Yamamoto
authors.forename: A
authors.initials: A
authors.lastname: Bracht
authors.forename: E L
authors.initials: EL
authors.lastname: Ishii-Iwamoto
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology*; D005934:Glucagon / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D008112:Liver Glycogen / Q000378:metabolism*; D008297:Male; D008727:Methotrexate / Q000494:pharmacology; D009288:Naproxen / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D008112:Liver Glycogen; D010656:Phenylephrine; D009288:Naproxen; D005934:Glucagon; D002118:Calcium; D008727:Methotrexate