DIFFERENTIAL EFFECT OF METABOLIC FUELS ON THE ENERGY-STATE AND NA-K+-ATPASE IN ISOLATED CEREBRAL MICROVESSELS()

Isolated bovine cerebral microvessels (ICMV) were incubated with diffe rent metabolic fuels to determine their ability to support microvessel Na+-K+-ATPase (quantitated as ouabain-sensitive Rb-86+ uptake) and th e ATP/ADP ratio. In comparison with ICMV incubated with glucose, Na+-K +-ATPase activity was reduced by 55% after a 3-h incubation in fuel-fr ee medium and by 30-40% after incubation with beta-hydroxybutyrate, ac etoacetate, or glutamate. However, Na+-K+-ATPase activity was not sign ificantly decreased in ICMV incubated with pyruvate or oleate plus car nitine. In contrast, only glucose was able to maintain the ATP/ADP rat io. To evaluate the effect of endogenous fatty acid metabolism on thes e parameters, ICMV were incubated with bromostearate, an inhibitor of fatty acid oxidation. Bromostearate decreased both Na+-K+-ATPase activ ity and the ATP/ADP ratio, even in the presence of glucose. These resu lts indicate that the varying effects of different fuels on Na+-K+-ATP ase in ICMV cannot be explained solely by their effects on the ATP/ADP ratio or on glycolytic ATP generation. They suggest that other fuel-m odulated factors play a key role in regulating this enzyme.