DERIVATION OF URINARY DOPAMINE FROM PLASMA DIHYDROXYPHENYLALANINE IN HUMANS

1. Dihydroxyphenylalanine is the precursor of all endogenous catechola mines. In laboratory animals, renal uptake and decarboxylation of circ ulating 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 (s pillover) of dihydroxyphenylalanine into arterial plasma. In experimen tal animals and in humans, dietary salt loading increases urinary excr etion of dihydroxyphenylalanine and dopamine. The present study examin ed in humans the extent to which circulating dihydroxyphenylalanine is the source of urinary dopamine and of the dopamine metabolite dihydro xyphenylacetic acid, and whether, as in animals, dietary salt loading affects dihydroxyphenylalanine spillover. 2. L-Dihydroxyphenylalanine (0.33 mug min-1 kg-1) was infused intravenously for 300 min after 7 da ys 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 i n antecubital venous plasma. Infusion of L-dihydroxyphenylalanine prod uced a steady-state mean dihydroxyphenylalanine level about 10 times t he endogenous level. About 30% of infused dihydroxyphenylalanine estim ated to be delivered to the kidneys via the arterial plasma was excret ed as dopamine, and about 30% was excreted as dihydroxyphenylacetic ac id. 3. Dietary salt loading increased urinary excretion rates of dihyd roxyphenylalanine [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 b e unchanged. 4. Renal uptake and decarboxylation of circulating dihydr oxyphenylalanine accounted for virtually all the urinary excretion of endogenous dopamine, but for only a minor portion of the excreted endo genous dihydroxyphenylacetic acid. 5. We conclude that in humans: (1) circulating dihydroxyphenylalanine is the main source of urinary dopam ine but only a minor source of urinary dihydroxyphenylacetic acid; and (2) increased spillover of endogenous dihydroxyphenylalanine does not account for the increased excretion of these compounds during salt lo ading.