The antinatriuretic action of gamma-L-glutamyl-5-hydroxy-L-tryptophan is dependent on its decarboxylation to 5-hydroxytryptamine in normal man.
1. The effects of inhibition of peripheral aromatic L-amino acid decarboxylase during infusion of the relatively renally selective 5-hydroxytryptamine (5-HT) prodrug, gamma-L-glutamyl-5-hydroxy-L-tryptophan (glu-5-HTP), were examined in eight healthy male subjects in a randomised, placebo-controlled, cross-over study. 2. Each subject received oral carbidopa (100 mg) or placebo followed, 1 h later, by a 60 min intravenous infusion of glu-5-HTP (16.6 micrograms kg-1 min-1) or placebo. 3. After administration of glu-5-HTP, cumulative urinary excretion of 5-HT was 430-fold greater than that after placebo, and was associated with a period of sodium retention. 4. Pretreatment with carbidopa substantially attenuated the increase in 5-HT excretion after glu-5-HTP and abolished its antinatriuretic effect. 5. These results are in keeping with the proposition that the antinatriuretic action of glu-5-HTP is dependent on its decarboxylation to 5-HT.
Li Kam Wa
T C
TC
Department of Medicine, University of Edinburgh, Royal Infirmary.
Freestone
S
S
Samson
R R
RR
Johnston
N R
NR
Lee
M R
MR
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D002230:Carbidopa / Q000008:administration & dosage / Q000494:pharmacology; D018592:Cross-Over Studies; D004151:Dipeptides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D011355:Prodrugs / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D012079:Renal Circulation / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism* / Q000652:urine; D012964:Sodium / Q000652:urine
D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D004151:Dipeptides; D011355:Prodrugs; C083320:gamma-glutamyl-5-hydroxytryptophan; D012701:Serotonin; D012964:Sodium; D002230:Carbidopa