RENAL METABOLISM AND EFFECTS OF THE GLUTAMYL DERIVATIVES OF L-DOPA AND 5-HYDROXYTRYPTOPHAN IN MAN

1. Equimolar amounts of gamma-L-glutamyl-L-3,4-dihydroxyphenylalanine (gludopa) and gamma-L-glutamyl-5-hydroxy-L-tryptophan were infused sep arately and together in eight healthy, salt-replete male subjects in a placebo-controlled, cross-over study to investigate whether the admin istration of one amine precursor affects the renal metabolism of the o ther and to determine whether dopamine or 5-hydroxytryptamine would be generated preferentially. The overall effect on sodium excretion was also measured when both precursors were administered simultaneously. 2 . Administration of gludopa was associated with marked increases in th e urinary excretion of L-dopa, dopamine and 3,4-dihydroxyphenylacetic acid, together with a rise in the urinary excretion of sodium, gamma-L -Glutamyl-5-hydroxy-L-tryptophan, on the other hand, produced marked i ncreases in the urinary excretion of 5-hydroxy-L-tryptophan, 5-hydroxy tryptamine and 5-hydroxyindoleacetic acid, and this was accompanied by a slight, but non-significant, reduction in sodium excretion. About 2 7% of the infused dose of gludopa (on a molar basis) was recovered in the urine as dopamine whereas 15% of the given dose of gamma-L-glutamy l-5-hydroxy-L-tryptophan was excreted as 5-hydroxytryptamine. 3. The u rinary excretion values of L-dopa, dopamine and 3,4-dihydroxyphenylace tic acid after the simultaneous infusion of gludopa and gamma-L-glutam yl-5-hydroxy-L-tryptophan were not significantly different from those observed after infusion of gludopa only, Similarly, the urinary excret ion values of 5-hydroxy-L-tryptophan, 5-hydroxytryptamine and 5-hydrox yindoleacetic acid during the co-infusion were similar to those measur ed after administration of gamma-L-glutamyl-5-hydroxy-L-tryptophan onl y. The net effect of the concomitant infusion of both glutamyl derivat ives was an increase in urinary sodium excretion. 4. Our study in salt -replete individuals suggests that dopamine rather than 5-hydroxytrypt amine was preferentially produced when equimolar amounts of their prec ursors were provided and that the natriuretic effect of dopamine, gene rated intrarenally from glu-dopa, was greater than the sodium retainin g action of 5-hydroxytryptamine derived from gamma-L-glutamyl-5-hydrox y-L-tryptophan. Comparison of the urinary metabolite data after the se parate and concomitant infusion of the two glutamyl compounds provided no evidence of competitive inhibition of synthesis of either amine.