Renal metabolism and effects of the glutamyl derivatives of L-dopa and 5-hydroxytryptophan in man. 1996

T C Li Kam Wa, and S Freestone, and R R Samson, and N R Johnston, and M R Lee
Department of Medicine, Royal Infirmary, Edinburgh, UK.

1. Equimolar amounts of gamma-L-glutamyl-L-3,4-dihydroxyphenylalanine (gludopa) and gamma-L-glutamyl-5-hydroxy-L-tryptophan were infused separately and together in eight healthy, salt-replete male subjects in a placebo-controlled, cross-over study to investigate whether the administration of one amine precursor affects the renal metabolism of the other 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 the 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 increases 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 27% 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-glutamyl-5-hydroxy-L-tryptophan was excreted as 5-hydroxytryptamine. 3. The urinary excretion values of L-dopa, dopamine and 3,4-dihydroxyphenylacetic acid after the simultaneous infusion of gludopa and gamma-L-glutamyl-5-hydroxy-L-tryptophan were not significantly different from those observed after infusion of gludopa only. Similarly, the urinary excretion values of 5-hydroxy-L-tryptophan, 5-hydroxytryptamine and 5-hydroxy-indoleacetic acid during the co-infusion were similar to those measured after administration of gamma-L-glutamyl-5-hydroxy-L-tryptophan only. The net effect of the concomitant infusion of both glutamyl derivatives was an increase in urinary sodium excretion. 4. Our study in salt-replete individuals suggests that dopamine rather than 5-hydroxytryptamine was preferentially produced when equimolar amounts of their precursors were provided and that the natriuretic effect of dopamine, generated intrarenally from gludopa, was greater than the sodium retaining action of 5-hydroxytryptamine derived from gamma-L-glutamyl-5-hydroxy-L-tryptophan. Comparison of the urinary metabolite data after the separate and concomitant infusion of the two glutamyl compounds provided no evidence of competitive inhibition of synthesis of either amine.

UI MeSH Term Description Entries
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D007980 Levodopa The naturally occurring form of DIHYDROXYPHENYLALANINE and the immediate precursor of DOPAMINE. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to DOPAMINE. It is used for the treatment of PARKINSONIAN DISORDERS and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system. L-Dopa,3-Hydroxy-L-tyrosine,Dopaflex,Dopar,L-3,4-Dihydroxyphenylalanine,Larodopa,Levopa,3 Hydroxy L tyrosine,L 3,4 Dihydroxyphenylalanine,L Dopa
D008297 Male Males
D004151 Dipeptides Peptides composed of two amino acid units. Dipeptide
D004295 Dihydroxyphenylalanine A beta-hydroxylated derivative of phenylalanine. The D-form of dihydroxyphenylalanine has less physiologic activity than the L-form and is commonly used experimentally to determine whether the pharmacological effects of LEVODOPA are stereospecific. Dopa,3,4-Dihydroxyphenylalanine,3-Hydroxy-DL-tyrosine,Dihydroxyphenylalanine Hydrochloride, (2:1),beta-Hydroxytyrosine,3 Hydroxy DL tyrosine,3,4 Dihydroxyphenylalanine,beta Hydroxytyrosine
D004298 Dopamine One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action. Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006897 Hydroxyindoleacetic Acid 5-HIAA,5-Hydroxy-3-Indoleacetic Acid,5-Hydroxyindolamine Acetic Acid,5 Hydroxy 3 Indoleacetic Acid,5 Hydroxyindolamine Acetic Acid,Acetic Acid, 5-Hydroxyindolamine,Acid, 5-Hydroxy-3-Indoleacetic,Acid, 5-Hydroxyindolamine Acetic,Acid, Hydroxyindoleacetic
D006916 5-Hydroxytryptophan The immediate precursor in the biosynthesis of SEROTONIN from tryptophan. It is used as an antiepileptic and antidepressant. 5-HTP,Hydroxytryptophan,Oxitriptan,Oxytryptophan,Tryptophan, 5-Hydroxy-,5 Hydroxytryptophan,5-Hydroxy- Tryptophan,Tryptophan, 5 Hydroxy
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults

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