Activation and desensitization of glycolysis by stimulation of adenylate cyclase in rat reticulocytes.
Isoproterenol or forskolin induce a 10-15-fold increase in concentration of cyclic AMP in rat reticulocytes as compared with the basal level of 2.3 +/- 0.3 microM. Glycolysis is stimulated by both compounds transiently more than 2-fold with a peak after 7.5 min followed by an exponential decline. The glycolytic rate in the presence of 10 microM isoproterenol or 10 microM forskolin did not return to basal levels within 60 min of incubation, but was depressed by as much as 50% under the influence of 100 microM forskolin. This phenomenon is designated as metabolic desensitization. The stimulation of glycolysis is probably due to activation of phosphofructokinase as well as to stimulation of Na+,K+-ATPase. The diminished glycolytic flux during the period of metabolic desensitization is accompanied by a decline of glucose 6-phosphate and in the presence of high concentrations of forskolin also by a decrease in glucose 1,6-bisphosphate. A lower rate of influx of glucose is postulated.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D005958:Glucosephosphates / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012156:Reticulocytes / Q000187:drug effects / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism; D013268:Stimulation, Chemical
D005958:Glucosephosphates; D005576:Colforsin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D000254:Sodium-Potassium-Exchanging ATPase; D007545:Isoproterenol; D015056:1-Methyl-3-isobutylxanthine