β1-adrenoceptor-stimulated lactate production in cultured astrocytes is predominantly glycogen-independent

Noradrenaline (NA) promotes breakdown of the glucose-polymer, glycogen, and hence enhances glycolytic production of lactate in astrocytes. Here, in cultured rat cerebrocortical astrocytes, we examined the contributions of different adrenoceptor subtypes to NA-modulated glucose metabolism, and the relationship of NA-induced glycogenolysis to lactate production. Stimulation of astrocytic glucose metabolism by NA was mediated predominantly via beta 1-adrenoceptors and cAMP. Constitutive beta 1-adrenoceptor activity - in the absence of exogenous NA - contributed to the basal rate of glycogen turnover. Although mRNAs encoding both beta 1- and beta 2-adrenoceptors were detected in these astrocytes, beta 2-adrenoceptors contributed little to NA-induced modulation of glucose metabolism. Activation of alpha 2- and alpha 1-adrenoceptors in these cells decreased cAMP and increased cytosolic Ca2+, respectively, but did not modulate NA-induced glycogenolysis: alpha 2-adrenoceptors because glycogenolysis was induced maximally by NA concentrations that only began to inhibit cAMP production; and alpha 1-adrenoceptors possibly because of desensitisation and depletion of Ca2+ stores. Under basal conditions, astrocytes converted glucose to extracellular lactate in near stoichiometric manner. When glucose-starved astrocytes were given fresh glucose-containing medium, lactate accumulation displayed a brief lag period before attaining a steady-state rate. During this lag period NA, acting at beta 1-adrenoceptors, increased the rate of lactate accumulation both in the absence and presence of an inhibitor of glycogen turnover. At the steady-state, the rate of glucose incorporation into accumulated glycogen was similar to 5% of that into lactate, but NA enhanced lactate output by 20-50%: this further indicates that NA, via beta 1-adrenoceptors and cAMP, can enhance astrocytic lactate production independently of its effect on glycogen turnover.