Role of microtubules in the regulation of metabolism in isolated cerebral microvessels

We used¹³C-labeled substrates and nuclearmagnetic resonance spectroscopy to examine carbohydrate metabolism invascular smooth muscle of freshly isolated pig cerebral microvessels(PCMV). PCMV utilized2-¹³C]glucose mainlyfor glycolysis, producing2-¹³C]lactate.Simultaneously, PCMV utilized the glycolytic intermediate 1-¹³C]fructose1,6-bisphosphate (FBP) mainly for gluconeogenesis, producing1-¹³C]glucose withonly minor3-¹³C]lactateproduction. The dissimilarity in metabolism of2-¹³C]FBP derivedfrom 2-¹³C]glucosebreakdown and metabolism of exogenous1-¹³C]FBPdemonstrates that carbohydrate metabolism is compartmented in PCMV.Because glycolytic enzymes interact with microtubules, we disruptedmicrotubules with vinblastine. Vinblastine treatment significantlydecreased2-¹³C]lactate peakintensity (87.8 ± 3.7% of control). The microtubule-stabilizing agent taxol also reduced2-¹³C]lactate peakintensity (90.0 ± 2.4% of control). Treatment with both agentsfurther decreased2-¹³C]lactateproduction (73.3 ± 4.0% of control). Neither vinblastine, taxol,or the combined drugs affected1-¹³C]glucose peakintensity (gluconeogenesis) or disrupted the compartmentation ofcarbohydrate metabolism. The similar effects of taxol and vinblastine, drugs that have opposite effects on microtubule assembly, suggest thatthey produce their effects on glycolytic rate by competing withglycolytic enzymes for binding, not by affecting the overall assemblystate of the microtubule network. Glycolysis, but not gluconeogenesis,may be regulated in part by glycolytic enzyme-microtubule interactions.