title: Inhibition of the different phosphodiesterase isoforms of rat heart cytosol by free fatty acids.
abstract: The sensitivity of the various phosphodiesterase (PDE) isoforms present in the cytosolic compartment of rat heart to the main fatty acids of the saturated, n-3 and n-6 families was assessed. High-performance liquid chromatography (HPLC) on a Mono Q ion-exchange column resolved four separate cyclic nucleotide phosphodiesterase activities: a calmodulin-activated fraction, a cyclic GMP-stimulated fraction, a cyclic AMP-specific rolipram-sensitive fraction, and a cyclic GMP-inhibited fraction. Polyunsaturated fatty acids (PUFA) were more potent inhibitors than saturated fatty acids whatever the considered PDE isoform. Although all PDE isoforms were affected, the cyclic GMP-stimulated isoform was the most sensitive to the inhibitory effect of PUFAs. The possible influences of free fatty acids (FFA) on cardiac contractility through PDE inhibition are discussed.
authors.affiliation: Unité INSERM 352, Laboratoire de Chimie Biologique, Institut National des Sciences Appliquées de Lyon, Villeurbanne, France.
authors.forename: M
authors.initials: M
authors.lastname: Dubois
authors.forename: M
authors.initials: M
authors.lastname: Picq
authors.forename: G
authors.initials: G
authors.lastname: Némoz
authors.forename: M
authors.initials: M
authors.lastname: Lagarde
authors.forename: A F
authors.initials: AF
authors.lastname: Prigent
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D002852:Chromatography, Ion Exchange; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D007527:Isoenzymes; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005230:Fatty Acids, Nonesterified; D005231:Fatty Acids, Unsaturated; D007527:Isoenzymes; D010726:Phosphodiesterase Inhibitors; D010727:Phosphoric Diester Hydrolases