Abstract

Glial cells transform glucose to a fuel substrate taken up and used by neurons. In the honeybee retina, photoreceptor neurons consume both alanine supplied by glial cells and exogenous proline. Ammonium (NH₄⁺) and glutamate, produced and released in a stimulus-dependent manner by photoreceptor neurons, contribute to the biosynthesis of alanine in glia. Here we report that NH₄⁺ and glutamate are transported into glia and that a transient rise in the intraglial concentration of NH₄⁺ or of glutamate causes a net increase in the level of reduced nicotinamide adenine dinucleotides [NAD(P)H]. Biochemical measurements indicate that this is attributable to activation of glycolysis in glial cells by the direct action of NH₄⁺ and glutamate on at least two enzymatic reactions: those catalyzed by phosphofructokinase (PFK; ATP:d-fructose-6-phosphotransferase, EC2.7.1.11) and glutamate dehydrogenase (GDH; l-glutamate:NAD oxidoreductase, deaminating; EC1.4.1.3). This activation leads to an increase in the production and release of alanine by glia. This signaling, which depends on the rate of conversion of NH₄⁺ and glutamate to alanine and α-ketoglutarate, respectively, in the glial cells, raises the novel possibility of a tight regulation of the nutritive function of glia.