Effect of monensin on deoxyglucose uptake in cultured astrocytes: energy metabolism is coupled to sodium entry.
This study was undertaken to measure the effect of maximal stimulation of sodium pump activity on the rate of energy metabolism in mouse cerebral astrocytes. The rate of uptake of 3H-2-deoxyglucose (3H-2-DG) was measured in astrocyte cultures sodium-loaded either by incubation in a K+-deficient solution or by use of the carboxylic sodium ionophore monensin. Sodium-loading by the first method caused 3H-2-DG uptake to increase by 80%, but the effect was brief (about 5 min) compared with the period of uptake measurement (20 min). In contrast, the presence of monensin (20 microM) caused a sustained 3.4-fold increase in the rate of 3H-2-DG uptake. The concentration-response relationship for monensin indicated a Kd of 1.5 microM and a maximum uptake enhancement of approximately fourfold. The monensin-stimulated uptake of 3H-2-DG was totally inhibited by incubation of the cultures in either K+-free or Na+-free solutions, or in the presence of ouabain (0.4 mM), indicating that the enhancement of uptake was the result of Na+ influx and sodium pump activation. These results raise the possibility that astroglia contribute significantly to regional variations in glucose consumption associated with functional activity in the brain. Ultrastructural analysis showed that sodium-loading in K+-free solution caused swelling confined to the trans face of Golgi stacks. However, monensin (5 microM) caused swelling of the entire Golgi stack, with progressively more severe swelling from cis to trans cisternae and formation of cytoplasmic vacuoles.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D002478:Cells, Cultured; D003837:Deoxy Sugars / Q000378:metabolism*; D003847:Deoxyglucose / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects*; D005663:Furans / Q000494:pharmacology*; D006056:Golgi Apparatus / Q000187:drug effects / Q000648:ultrastructure; D051379:Mice; D008854:Microscopy, Electron; D008985:Monensin / Q000494:pharmacology*; D010042:Ouabain / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism*
D003837:Deoxy Sugars; D005663:Furans; D010042:Ouabain; D008985:Monensin; D003847:Deoxyglucose; D012964:Sodium