Inhibition of glutamine transport depletes glutamate and GABA neurotransmitter pools: further evidence for metabolic compartmentation

• DOI: 10.1046/j.1471-4159.2003.01713.x
• Publication Date: 2008-02-07T18:48:34Z
• Authors: Caroline Rae; Nathan Hare; William A. Bubb; Sally R. McEwan; Angelika Bröer; James A. McQuillan; Vladimir J. Balcar; Arthur D. Conigrave; Stefan Bröer
• Keywords: Alanine; Glutaminase

The role of glutamine and alanine transport in the recycling neurotransmitter glutamate was investigated Guinea pig brain cortical tissue slices prisms, cultured neuroblastoma astrocyte cell lines. ability exogenous (2 mm) to displace 13C label supplied as [3-13C]pyruvate, [2-13C]acetate, l-[3-13C]lactate, or d-[1-13C]glucose using NMR spectroscopy. Glutamine inhibited under quiescent depolarising conditions histidine, which shares most routes with glutamine, 2-(methylamino)isobutyric acid (MeAIB), a specific inhibitor neuronal system A. mainly entered large, slow turnover pool, probably located neurons, did not interact glutamate/glutamine cycle. This uptake by MeAIB. When [1-13C]glucose used substrate, cycle histidine but MeAIB, suggesting that A may play prominent cycling. blocked conditions, pools were depleted, showing is essential for maintenance glutamate, GABA pools. Alanine labelling release decreased released from neurons returned astrocytes. resultant implications metabolic compartmentation regulation metabolism processes are discussed.