Interactions between cAMP- and cGMP-dependent protein kinase inhibitors and phosphodiesterase IV inhibitors on arachidonate release from human monocytes |
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Affiliation: | 1. LIAAD, INESC TEC, Faculdade de Economia, Universidade do Porto Rua Dr. Roberto Frias s/n, 4200-464, Porto, Portugal;2. Mathematical Optimization and Planning, Amazon.com, 333 Boren Avenue North, Seattle, WA 98109, USA;1. Centre d''expertise en analyse environnementale du Québec, ministère du Développement durable, de l''Environnement et de la Lutte contre les changements climatiques, 2700 rue Einstein, Québec GIP 3W8, Canada;2. Université du Lorraine, LIEC, CNRS UMR 7360, Avenue du Général Delestraint, F-57070 Metz, France;3. IRSTEA, HBAN, Direction Régionale d''Antony, 1 Rue Pierre-Gilles de Gennes, CS10030, F-92761 Antony Cedex, France;4. GRIL, Département de Sciences Biologiques, Université de Montréal, C.P. 6128, Succ. Centre-Ville, Montréal H3C 3J7, Québec, Canada |
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Abstract: | The effects of specific inhibitors of cAMP-dependent protein kinase (PKA) and cGMP-dependent protein kinase (PKG) on the inhibitory activity of phosphodiesterase (PDE) type IV inhibitors and of the cell permeable analogue of cAMP, db-cAMP, were investigated on fMLP-induced arachidonate release from human monocytes. When monocytes were preincubated with the combined PKA/PKG inhibitor H8 (10−6 to 10−4 M) or the selective PKG inhibitor Rp-8-cpt-cGMPs (10−6 to 10−4 M) a concentration-dependent reduction of the inhibitory effect of db-cAMP (10− M), rolipram (10−5 M) and Ro 20-1724 (10−5 M) was noted. When monocytes were preincubated with the selective PKA inhibitor H89 (10−6 to 10−4 M), only a small inhibition of the effect of db-cAMP and no inhibition of the effects of rolipram and Ro 20–1724 were observed. The present data indicate that db-cAMP and PDE IV inhibitors elicit an in vitro anti-inflammatory activity by a PKA-independent mechanism, which do not appear to be mainly mediated via the PKG activation. |
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