A DECREASED TUBULAR UPTAKE OF DOPA RESULTS IN DEFECTIVE RENAL DOPAMINE PRODUCTION IN AGED RATS

A major proportion of urinary dopamine derives from the renal decarbox ylation of circulating dopa. This study evaluates the effects of aging on renal production of dopamine using 3- and 12-mo-old male Wistar ra ts. Urinary excretion of Na+, norepinephrine (NE), 3,4-dihydroxyphenyl glycol, and dopa were similar in the two groups. Urinary dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) were lower in older animals (do pamine, 20 +/- 6 vs. 47 +/- 7 nmol/24 h, P < 0.001; DOPAC, 142 +/- 36 vs. 304 +/- 56 nmol/24 h, P < 0.03). Urinary 3-O-methyldopa (OM-dopa) was higher in 12-mo-old rats (6.2 +/- 2.0 vs. 3.3 +/- 0.20 nmol/24 h, P < 0.03). Levels of dopa and NE in renal cortex from 12-mo-old rats w ere higher (P < 0.001) than in younger animals. Dopamine content in re nal cortex from 3-mo-old rats was 295 +/- 64 pmol/g, whereas it was un detectable in 12-mo-old animals. Aromatic-L-amino-acid decarboxylase a nd monoamine oxidase activities were higher (P < 0.001) in renal corte x from 12-mo-old animals. Catechol-O-methyltransferase activity was si milar in both groups. The uptake of dopa by the luminal membrane was e xplored using brush-border membrane vesicles. The Na+-gradient-driven (100 mM) uptake of dopa into vesicles from 3-mo-old animals showed at 10 s an overshoot threefold greater than the equilibrium uptake. The o vershoot was blunted in 12-mo-old rats. Maximal uptake of L-[H-3]dopa at 10 s in 3-mo-old rats was higher than in older animals (169 +/- 16 vs. 52 +/- 7 pmol . mg protein(-1). min(-1), P < 0.01), whereas the Mi chaelis constant was similar in both groups. These results show a defe ct in renal dopamine production in 12-mo-old rats that, to some extent , appears to be derived from a decreased uptake of dopa by tubular bru sh-border membranes.