PT - JOURNAL ARTICLE AU - CLAUDE F. POYART AU - GABRIEL G. NAHAS AU - YVONNE VULLIEMOZ TI - Inhbition of Activated Lipolysis by Acidosis DP - 1968 Jul 01 TA - Molecular Pharmacology PG - 389--401 VI - 4 IP - 4 4099 - http://molpharm.aspetjournals.org/content/4/4/389.short 4100 - http://molpharm.aspetjournals.org/content/4/4/389.full SO - Mol Pharmacol1968 Jul 01; 4 AB - Rat epididymal adipose tissue was incubated in Krebs-Ringer phosphate medium with 5% albumin without glucose and with glucagon, ACTH, norepinephrine, or cyclic 3',5'-AMP dibutyrate. pH of the medium was varied from 7.4 to 6.6. Glycerol release was measured and taken as the index of lipolytic activity. In a first series of experiments at pH 7.4, ACTH and glucagon-activated lipolysis was potentiated by increasing doses of theophylline. In a second series, with pH of the medium at 6.6, the lipolytic effects of these two hormones were significantly inhibited. When theophylline (10-2 M) was added in combination with optimal doses of the hormones, the rate of glycerol release was similar at normal and acid pH. These results were interpreted as indicating that H+ might exert its inhibitory effect on a common mechanism which results in cyclic 3',5'-AMP formation. This hypothesis was confirmed in a third series: when cyclic 3',5'-AMP dibutyrate (10-3 M) was added to the medium, similar glycerol release was found at pH 7.4 and 6.6. When combined with norepinephrine, cyclic 3',5'-AMP dibutyrate also reversed the inhibitory effects of acidosis. In a last series of experiments, it was shown that acidosis did not alter irreversibly the sites of action of the lipolytic agents. These results, when analyzed according to the drug-receptor theory, would indicate that acidosis might inhibit, at least in part, the different lipolytic drugs used in this study by hindering the formation of the drug-receptor complexes that activate lipolysis. ACKNOWLEDGMENT We wish to thank Dr. Lubos Triner for his help and guidance in the planning of these experiments.