KETONE-BODIES PROMOTE A RAPID RISE IN GLUTAMATE EFFLUX FROM THE ISOLATED-PERFUSED RAT-LIVER WITHOUT ALTERING THE RATE OF GLUTAMINE PRODUCTION

Livers of starved (48 hr) male Wistar rats were perfused in a non reci rculating manner with a near physiological mix of ammonium, lactate, o rnithine and pyruvate in Krebs buffer. The addition of ketone bodies ( 3-DL-hydroxybutyrate [B OHB] 2-30 mM or lithium-acetoacetate (15 mM) t o the perfusate resulted in a rapid rise in the efflux of glutamate fr om the liver (five times above basal). This was not seen with control solutions (sodium chloride or lithium chloride). The increased efflux was sustained for the duration of the addition of the ketone bodies (7 min), was rapidly reversible and dose dependant. Glutamine export rat es were not altered, suggesting that either the glutamate originated f rom cells not responsible for glutamine synthesis or that this glutama te was superfulous to the requirement of glutamine synthesis. There wa s no evidence that the lactate transporter was involved in the entry o f lactate into perivenous hepatocytes for glutamine synthesis; lactate presumably entering the hepatocyte by an alternative pathway, probabl y nonionic diffusion.