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 different metabolic fuels to determine their ability to support microvessel Na(+)-K(+)-ATPase (quantitated as ouabain-sensitive 86Rb+ uptake) and the 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-free medium and by 30-40% after incubation with beta-hydroxybutyrate, acetoacetate, or glutamate. However, Na(+)-K(+)-ATPase activity was not significantly decreased in ICMV incubated with pyruvate or oleate plus carnitine. In contrast, only glucose was able to maintain the ATP/ADP ratio. To evaluate the effect of endogenous fatty acid metabolism on these parameters, ICMV were incubated with bromostearate, an inhibitor of fatty acid oxidation. Bromostearate decreased both Na(+)-K(+)-ATPase activity and the ATP/ADP ratio, even in the presence of glucose. These results indicate that the varying effects of different fuels on Na(+)-K(+)-ATPase in ICMV cannot be explained solely by their effects on the ATP/ADP ratio or on glycolytic ATP generation. They suggest that other fuel-modulated factors play a key role in regulating this enzyme.
Sussman
I
I
Evans Department of Medicine, Boston University School of Medicine, Massachusetts 02118.
Schultz
V
V
Gupta
S
S
Grady
C
C
Ruderman
N B
NB
Tornheim
K
K
D020155:3-Hydroxybutyric Acid; D000090:Acetoacetates / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002331:Carnitine / Q000494:pharmacology; D002417:Cattle; D002560:Cerebrovascular Circulation; D004734:Energy Metabolism / Q000187:drug effects*; D005947:Glucose / Q000494:pharmacology; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D006885:Hydroxybutyrates / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008833:Microcirculation / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D011773:Pyruvates / Q000494:pharmacology; D019289:Pyruvic Acid; D012413:Rubidium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D000090:Acetoacetates; D005971:Glutamates; D006885:Hydroxybutyrates; D009829:Oleic Acids; D011773:Pyruvates; D019301:Oleic Acid; D018698:Glutamic Acid; C016635:acetoacetic acid; D010042:Ouabain; D000244:Adenosine Diphosphate; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate; D000254:Sodium-Potassium-Exchanging ATPase; D005947:Glucose; D012413:Rubidium; D002331:Carnitine; D020155:3-Hydroxybutyric Acid