A decreased tubular uptake of dopa results in defective renal dopamine production in aged rats

Document Type

Journal Article

Publication Date

1-1-1995

Journal

American Journal of Physiology - Renal Fluid and Electrolyte Physiology

Volume

268

Issue

6 37-6

DOI

10.1152/ajprenal.1995.268.6.f1087

Keywords

3,4- dihydroxyphenylacetic acid; 3,4-dihydroxyphenylglycol; 3-O-methyldopa; aging; amino acid decarboxylase; catechol-O-methyltransferase; monoamine oxidase; norepinephrine; sodium

Abstract

A major proportion of urinary dopamine derives from the renal decarboxylation of circulating dopa. This study evaluates the effects of aging on renal production of dopamine using 3- and 12-me-old male Wistar rats. Urinary excretion of Na+, norepinephrine (NE), 3,4- dihydroxyphenylglycol, and dopa were similar in the two groups. Urinary dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) were lower in older animals (dopamine, 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 were higher (P < 0.001) than in younger animals. Dopamine content in renal cortex from 3-mo- old rats was 295 ± 64 pmol/g, whereas it was undetectable in 12-mo-old animals. Aromatic-L-amino-acid decarboxylase and monoamine oxidase activities were higher (P < 0.001) in renal cortex from 12-mo-old animals. Catechol-O- methyltransferase activity was similar in both groups. The uptake of dopa by the luminal membrane was explored 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 overshoot was blunted in 12-mo-old rats. Maximal uptake of L- [3H]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 Michaelis constant was similar in both groups. These results show a defect 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 brush-border membranes.

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