Effects of L-isopropylnorepinephrine, 3-isobutyl-1-methyl xanthine and dibutyryl cyclic AMP on hexose uptake and metabolism by rat striatal slices.

Abstract— Rat striatal slices in vitro undergo a number of changes in the pattern of their carbohydrate metabolism when incubated with either dibutyryl cyclic AMP or with the beta-adrenergic agonist l -isopropylnorepinephrine (IPNE) plus the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). We have, in previous reports, shown that the content of glycogen in the slices is reduced by approx 50% upon incubation with these agonists. We now report that the rate of hexose uptake as measured by ³H uptake from a medium containing 1 mm -glucose with a trace of [³H]2-deoxyglucose (2-DOG) is reduced by 20–25% compared to basal uptake rates. The rate of lactic acid production by the slices is approximately doubled and a small decrease in O₂ uptake is also observed. The data are consistent with the conversion of the metabolism of a population of glycogen-containing cells in the slises, upon incubation with dibutyryl cyclic AMP or TBMX + IPNE, from primarily oxidative metabolism using an extracellular glucose source to primarily glycolytic metabolism using the cells’ own glycogen stores. The findings reported here in vitro are in good agreement with studies reported in the literature concerning changes in the in vivo levels of brain glycogen and lactic acid in mice following the injection of drugs which act upon beta-adrenergic receptors.