A comparison of the renal and neuroendocrine effects of two 5-hydroxytryptamine renal prodrugs in normal man.
1. The effects of 1 h intravenous infusions of equimolar amounts (45 nmol min-1 kg-1) of two putative 5-hydroxytryptamine renal prodrugs, 5-hydroxy-L-tryptophan and gamma-L-glutamyl-5-hydroxy-L-tryptophan, were investigated in a randomized, placebo-controlled, cross-over study in nine healthy male subjects. 2. Cumulative urinary 5-hydroxytryptamine excretion over the 3 h observation period rose by about 370-fold after 5-hydroxy-L-tryptophan and 390-fold after gamma-L-glutamyl-5-hydroxy-L-tryptophan when compared with placebo infusion. Urinary 5-hydroxy-L-tryptophan excretion was three times higher after administration of gamma-L-glutamyl-5-hydroxy-L-tryptophan than after 5-hydroxy-L-tryptophan infusion. Urinary 5-hydroxyindole-3-acetic acid excretion after 5-hydroxy-L-tryptophan infusion was significantly greater than that after gamma-L-glutamyl-5-hydroxy-L-tryptophan administration. Urinary dopamine excretion was not affected by either compound when compared with placebo. 3. 5-Hydroxy-L-tryptophan significantly reduced urine flow rate and urinary sodium excretion. gamma-L-Glutamyl-5-hydroxy-L-tryptophan was antinatriuretic but did not affect urine output. These changes occurred without significant alterations in effective renal plasma flow and glomerular filtration rate. 4. Both 5-hydroxy-L-tryptophan and gamma-L-glutamyl-5-hydroxy-L-tryptophan significantly increased plasma aldosterone concentration without a concomitant rise in plasma renin activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Li Kam Wa
T C
TC
Department of Medicine, Royal Infirmary, Edinburgh, U.K.
Freestone
S
S
Samson
R R
RR
Johnson
N R
NR
Lee
M R
MR
D006916:5-Hydroxytryptophan / Q000494:pharmacology* / Q000652:urine; D000328:Adult; D000450:Aldosterone / Q000097:blood; D001794:Blood Pressure; D004298:Dopamine / Q000652:urine; D005919:Glomerular Filtration Rate; D006339:Heart Rate; D006801:Humans; D007668:Kidney / Q000502:physiology*; D008297:Male; D011355:Prodrugs / Q000494:pharmacology*; D017597:Renal Blood Flow, Effective; D012083:Renin / Q000097:blood; D012701:Serotonin / Q000652:urine; D012964:Sodium / Q000652:urine; D014554:Urination
D011355:Prodrugs; D012701:Serotonin; D000450:Aldosterone; D012964:Sodium; D006916:5-Hydroxytryptophan; D012083:Renin; D004298:Dopamine