title: Stimulation of fatty acid oxidation by phosphodiesterase III inhibitors in rat myocytes.
abstract: In order to study the regulation of fatty acid oxidation in the heart, the effects of some phosphodiesterase III inhibitors, such as enoximone and milrinone, on the oxidation of [1-14C]palmitic acid, [1-14C]octanoic acid, and [2-14C]pyruvate were studied in adult rat myocytes. Enoximone and milrinone, at a concentration of 0.25 mM, increased palmitate oxidation significantly, by 70 and 40%, respectively. Also, enoximone increased octanoate oxidation by 45%. In contrast, pyruvate oxidation was decreased by 60% by enoximone. To investigate the effects of enoximone or milrinone on the pathway of fatty acid oxidation, their effects on the oxidation of either [1-14C]palmitoyl-CoA or [1-14C]palmitoylcarnitine were studied with rat heart homogenates. Neither enoximone nor milrinone had any effects on the oxidation of these compounds. Compounds known to elevate intracellular [Ca2+] or cyclic AMP, such as the calcium ionophore A23187, ionomycin, dibutyryl cyclic AMP, or isoproterenol, had no effect on palmitate oxidation. Enoximone, at a concentration of 0.25 mM, increased palmitate uptake by 40% in rat myocytes. These results suggest that enoximone and milrinone increase fatty acid oxidation in myocytes by increasing their cellular transport, and they also show the usefulness of these compounds as a tool to study the regulation of this vital pathway in heart.
authors.affiliation: Department of Pharmacology, Glaxo Inc., Research Triangle Park, North Carolina.
authors.forename: S
authors.initials: S
authors.lastname: Abdel-aleem
authors.forename: C
authors.initials: C
authors.lastname: Frangakis
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D017335:Enoximone; D006321:Heart / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D020105:Milrinone; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D010168:Palmitates / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011728:Pyridones / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D007093:Imidazoles; D010168:Palmitates; D010726:Phosphodiesterase Inhibitors; D011728:Pyridones; D017335:Enoximone; D020105:Milrinone