Arachidonic acid stimulates glucose uptake in cerebral cortical astrocytes.

Abstract

Arachidonic acid (AA) has recently been shown to influence various cellular functions in the central nervous system. Here we report that AA increases, in a timeand concentration-dependent manner, 2-deoxy-D- [1-3H] uptake, for which the EC50 of NE is 1 IAM. Since the cerebral cortex, the brain region from which astrocytes used in this study were prepared, receives a massive noradrenergic innervation, originating from the locus coeruleus, the effects of NE reported here further stress the notion that certain neurotransmitters may play a role in the regulation of energy metabolism in the cerebral cortex and point at astrocytes as the likely targets of such metabolic effects.Astrocytes play an important role in the maintenance of local homeostasis within the central nervous system (1, 2). In addition to clearing the extracellular space from K+, glutamate, or 'y-aminobutyric acid, whose levels increase as a result of neuronal activity (3)(4)(5), astrocytes may contribute to energy metabolism homeostasis, a function already postulated over a century ago by Golgi (6). For example, astrocytes are the cell type in which glycogen is almost exclusively stored within the central nervous system (7,8), and certain neurotransmitters can readily mobilize this energy reserve (9, 10). Thus, vasoactive intestinal peptide (VIP) and norepinephrine (NE), two neurotransmitters contained in discrete neuronal populations in the cerebral cortex (11), promote, within minutes of application, glycogenolysis in primary cultures of astrocytes (12); within a longer time frame (4-8 hr), these two neurotransmitters promote glycogen resynthesis (13 (29), and elevated extracellular K+ (30). Given the role that astrocytes play in the regulation of energy metabolism in the central nervous system, we set out to determine the consequences of manipulating AA metabolism on glucose uptake in astrocytes. MATERIALS AND METHODS AA was purchased from Nu Chek Prep (Elysian, MN);[3H]2DG (specific activity, 17.3 Ci/mmol; 1 Ci = 37 GBq) and [3H]AA (specific activity, 200 Ci/mmol) were from Amersham. Fetal calf serum (FCS) was purchased from Seromed (Berlin), while Dulbecco's modified Eagle's medium (DMEM) and all other chemicals were from Sigma. AA was dissolved in hexan (1 mg/ml) and stored as a stock solution at -70°C. On the day ofthe experiment, an aliquot was taken, evaporated under a stream of nitrogen, resuspended in 1 ml of diluted [3H]

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