Net interorgan transport of L-glutamate in rats occurs via the plasma, not via erythrocytes.

Glutamate is concentrated within RBC, but this intracellular glutamate is often ignored in studies of glutamate metabolism in vivo. The objective of this work was to determine the size of the plasma and cellular glutamate pools in rat blood and to clarify the role of RBC in the interorgan transport of glutamate. Approximately 20% of whole-blood glutamate was associated with isolated RBC membranes, but this was easily removed by washing with high salt solutions. Arterial plasma glutamate levels were relatively stable and did not show marked differences with starvation, streptozotocin diabetes or feeding 60% casein diets. In rats fed 5% casein, the plasma glutamate level was slightly higher (P < 0.05) than in most other groups. In contrast, RBC glutamate levels showed considerable variation. In rats consuming 5% casein, cellular glutamate levels were approximately 100% higher (P < 0.05) than in control, starved, diabetic or 20 or 60% casein-fed rats. Cellular glutamate levels were also higher (P < 0.05) in rats fed 60% casein than in those consuming 20% casein or the control diet. Rat erythrocytes in vitro did not take up or release free glutamate, confirming that they do not possess a glutamate transporter. Arteriovenous difference measurements across the portal drained viscera indicated a net glutamate release into the portal vein in control, 60% casein-fed and diabetic rats. In all cases, the net change in blood glutamate across the tissue occurred via the plasma, with no change in cellular glutamate levels. Therefore analyses of glutamate metabolism in rats in vivo may be made confidently using measurements of either whole-blood or plasma glutamate concentrations.