Effect of Na⁺ on intestinal succinate transport and metabolism in vitro

The effect of Na⁺ on ¹⁴CO₂ production from [¹⁴C]succinate was studied in isolated rat enterocytes, and Na⁺-dependent succinate transport was characterized in pig intestinal brush-border membrane vesicles. The production of ¹⁴CO₂ from [¹⁴C]succinate by enterocytes was decreased 12-fold when Na⁺ was replaced by N-methyl-D-glucamine in the absence of glutamine and 20-fold in the presence of 0.2 or 0.5 mM glutamine. The ratio of ¹⁴CO₂ produced from [1,4-¹⁴C]succinate to that produced by [2,3-¹⁴C]succinate was not affected by Na⁺ replacement, indicating that the pattern of tricarboxylic acid cycle metabolism was not altered. The uptake of [¹⁴C]succinate by brush-border membrane vesicles was stimulated 10-fold in the presence of 100 mM NaCl compared with 100 mM KCl. When succinate uptake was correlated to transport into an osmotically sensitive space, the magnitude of the Na⁺ stimulation was 20-fold. Succinate transport into brush-border membrane vesicles was Na⁺ dependent, electroneutral, nonconcentrative, with an apparent Na⁺-succinate coupling ratio of 2:1. Results of this study indicate that Na⁺-stimulated CO₂ production by enterocytes can be explained by the effect of Na⁺ on succinate transport across the brush-border membrane.