Derivation of urinary dopamine from plasma dihydroxyphenylalanine in humans.
1. Dihydroxyphenylalanine is the precursor of all endogenous catecholamines. In laboratory animals, renal uptake and decarboxylation of circulating dihydroxyphenylalanine accounts for most of dopamine in urine. Dopamine is natriuretic, and in rats, dietary salt loading increases renal dihydroxyphenylalanine uptake by increasing the rate of entry (spill-over) of dihydroxyphenylalanine into arterial plasma. In experimental animals and in humans, dietary salt loading increases urinary excretion of dihydroxyphenylalanine and dopamine. The present study examined in humans the extent to which circulating dihydroxyphenylalanine is the source of urinary dopamine and of the dopamine metabolite dihydroxyphenylacetic acid, and whether, as in animals, dietary salt loading affects dihydroxyphenylalanine spillover. 2. L-Dihydroxyphenylalanine (0.33 micrograms min-1 kg-1) was infused intravenously for 300 min after 7 days of a low-salt (mean 41 mmol/day) or a high-salt (mean 341 mmol/day) diet in 12 healthy subjects. Concentrations of dihydroxyphenylalanine, dopamine and dihydroxyphenylacetic acid were measured in urine and in antecubital venous plasma. Infusion of L-dihydroxyphenylalanine produced a steady-state mean dihydroxyphenylalanine level about 10 times the endogenous level. About 30% of infused dihydroxyphenylalanine estimated to be delivered to the kidneys via the arterial plasma was excreted as dopamine, and about 30% was excreted as dihydroxyphenyl-acetic acid. 3. Dietary salt loading increased urinary excretion rates of dihydroxyphenylalanine [from 0.08 +/- (SEM) 0.01 to 0.14 +/- 0.03 nmol/min, t = 2.80, P < 0.02] and dopamine (from 1.03 +/- 0.19 to 1.30 +/- 0.28 nmol/min, t = 2.35, P < 0.05), whereas dihydroxyphenylalanine spillover appeared to be unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
Clinical Neuroscience Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892.
E
E
Wolfovitz
E
E
Grossman
C J
CJ
Folio
H R
HR
Keiser
I J
IJ
Kopin
D S
DS
Goldstein
D015102:3,4-Dihydroxyphenylacetic Acid / Q000652:urine; D000328:Adult; D004295:Dihydroxyphenylalanine / Q000097:blood* / Q000652:urine; D004298:Dopamine / Q000652:urine*; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D007980:Levodopa / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D012982:Sodium, Dietary / Q000008:administration & dosage
D012982:Sodium, Dietary; D015102:3,4-Dihydroxyphenylacetic Acid; D007980:Levodopa; D004295:Dihydroxyphenylalanine; D004298:Dopamine