Stimulation of polyunsaturated fatty acid oxidation in myocytes by regulating its cellular uptake. On the rate limiting step of polyunsaturated fatty acid oxidation in heart.
In order to investigate the regulation of polyunsaturated fatty acid oxidation in the heart, the effect of the phosphodiesterase inhibitor enoximone on the oxidation of [1-14C] arachidonic acid, and [1-14C] arachidonyl-CoA, were studied in adult rat myocytes, and isolated rat heart mitochondria. Enoximone stimulated arachidonate oxidation by 94%, at a concentration of 0.25 mM. The apparent Vmax value of arachidonate oxidation in the presence of enoximone (6.98 nmol/mg protein/30 min), was approximately 75% higher than the value observed with the control (4.0 nmol/mg protein/30 min) in isolated myocytes. Also, enoximone stimulated arachidonate uptake by 27% at a concentration of 0.25 mM. On the other hand, enoximone had no effect on the oxidation of [1-14C] arachidonyl-CoA in isolated rat heart mitochondria. These results suggest that the oxidation of polyunsaturated fatty acids in myocytes is regulated by the rate of uptake of these acids across sarcolemmal membranes.
Abdel-aleem
S
S
Glaxo Inc., Department of Pharmacology, Research Triangle Park, NC 27709.
Badr
M
M
Frangakis
C
C
D000214:Acyl Coenzyme A / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001692:Biological Transport; D017335:Enoximone; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism; D009132:Muscles / Q000166:cytology / Q000378:metabolism*; D010084:Oxidation-Reduction; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D000214:Acyl Coenzyme A; D001095:Arachidonic Acids; D005231:Fatty Acids, Unsaturated; D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; C026563:arachidonyl-coenzyme A; D016718:Arachidonic Acid; D017335:Enoximone