Molecular specificity of the tubular resorption of "acidic" amino acids. A continuous microperfusion study in rat kidney in vivo.

Single sections of superficial proximal convolutions of rat kidney were microperfused in vivo and in situ. The perfusion fluids contained radioactively labelled L- or D-aspartate, L-glutamate, L-pyroglutamate, or N-methyl-D-aspartate. L-gamma-Carboxyglutamate as well as the other amino acids were added in the unlabelled form. Results. L- and D-Aspartate (0.073 mmol X 1(-1)) are quickly resorbed at about the same rate. D-Aspartate resorption was blocked by L-aspartate (5 mmol X 1(-1)) but not by beta-alanine (5 mmol X 1(-1)). L-Aspartate resorption was inhibited by L-glutamate (2 mmol X 1(-1)) but not by D-glutamate, L-asparagine, L-phenylalanine or by succinate (2 mmol X 1(-1), each). The fast resorption of L-glutamate (0.073 mmol X 1(-1)) was blocked by D-aspartate, L-cysteate (2 mmol X 1(-1)), but not by 3-mercaptopicolinic acid (0.15 mmol X 1(-1)), L-glutamine, 2-oxoglutarate, taurine, N-methyl-L-glutamate or kainic acid (2 mmol X 1(-1), each). L-gamma-Carboxyglutamate (0.66 mmol X 1(-1)) and N-methyl-D-aspartate (2 mumol X 1(-1)) were found to be resorbed only at an extremely small rate. L-Pyroglutamate (0.076 mmol X 1(-1)) resorption was not influenced by L-glutamate (1 mmol X 1(-1)). Fractional excretion of gamma-carboxyglutamate was 7-25% (L-form) or 45-70% (D-form) at an artificially elevated plasma level of 12 mumol X 1(-1). It is concluded that L- and D-aspartate, L-glutamate, L-cysteate and, to a much smaller extent, L-gamma-carboxyglutamate, are accepted by the tubular resorption mechanism highly specific for "acidic" amino acids. N-Substitution, the amidation of the beta- or gamma-carboxyl group, or the removal of the alpha-amino moiety almost completely abolish the ability of such compounds to be resorbed via this carrier; N-methylated or gamma-carboxylated derivatives of "acidic" amino acids are not resorbed at all from the proximal tubule. The resorption of glutamate, but not of aspartate, is highly stereospecific.