Induction of microsomal stearoyl-CoA desaturase by the administration of various phenoxyacetic acid derivatives.
The potency of seven phenoxyacetic acid derivatives to induce microsomal stearoyl-CoA desaturation activity in rat liver was compared with that of 2-(4-chlorophenoxy)-2-methyl-propionic acid (clofibric acid). These compounds were given to rats with diet. Of seven phenoxyacetic acid derivatives tested, both 2-(4-chlorophenoxy)-propionic acid and 2-(2-chlorophenoxy)-2-methyl-propionic acid increased considerably the desaturation activity as was observed with clofibric acid. Moreover, 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) also increased the desaturation activity, although the inducing effect on desaturation activity was very weak compared to that of clofibric acid. These three compounds increased activity of terminal desaturase without accompanying marked changes in reduced nicotinamide adenine dinucleotide (NADH)-cytochrome b5 reductase activity and cytochrome b5 content as was the case with clofibric acid. The other four phenoxyacetic acid derivatives, 2-(phenoxy)-propionic acid, 4-chlorophenoxyacetic acid, 2-chlorophenoxyacetic acid and 2, 4-dichlorophenoxyacetic acid (2,4-D) changed scarcely the desaturation activity. These compounds had no influence on NADH-cytochrome b5 reductase activity, cytochrome b5 content and terminal desaturase activity. Correlating with the changes in the desaturation activity, concentration of octadecenoic acid was increased in hepatic microsomes, whole liver and serum. Treatment with clofibric acid did not change the concentration of octadecenoic acid in brain, lung, heart, spleen, testis and adipose tissue.
D015085:2,4,5-Trichlorophenoxyacetic Acid / Q000494:pharmacology; D015084:2,4-Dichlorophenoxyacetic Acid / Q000494:pharmacology; D000214:Acyl Coenzyme A / Q000378:metabolism*; D000818:Animals; D002995:Clofibric Acid / Q000494:pharmacology; D003579:Cytochrome Reductases / Q000096:biosynthesis; D042966:Cytochrome-B(5) Reductase; D004790:Enzyme Induction / Q000187:drug effects; D006016:Glycolates / Q000494:pharmacology*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D009829:Oleic Acids / Q000032:analysis; D010084:Oxidation-Reduction; D010642:Phenoxyacetates / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D000214:Acyl Coenzyme A; D006016:Glycolates; D009829:Oleic Acids; D010642:Phenoxyacetates; D015084:2,4-Dichlorophenoxyacetic Acid; C017725:stearoyl-coenzyme A; D002995:Clofibric Acid; D015085:2,4,5-Trichlorophenoxyacetic Acid; D003579:Cytochrome Reductases; D042966:Cytochrome-B(5) Reductase