Involvement of tubular sodium in the formation of dopamine in the human renal cortex.
This study has examined the influence of sodium (0, 20, 40, 80, 120, and 160 mM) and ouabain (100, 500, and 1,000 microM), an inhibitor of the enzyme Na(+)-K+ ATPase, on the synthesis of dopamine in slices of human renal cortex loaded with exogenous L-dihydroxyphenylalanine (L-DOPA). The deamination of newly formed dopamine into 3,4-dihydroxyphenylacetic acid (DOPAC) was also examined. The formation of dopamine and its deamination to DOPAC in slices and homogenates of human renal cortex closely depended on the concentration of L-DOPA added to the medium; in homogenates of renal cortex, the production of dopamine was found to be 74% of that occurring in the renal medulla. Decarboxylation of L-DOPA was found saturable at 1,000 microM L-DOPA, which had Vmax and Km values for L-amino acid decarboxylase activity of, respectively, 5.8 +/- 0.6 nmol/mg of protein per hour and 62 +/- 8 microM. The accumulation of newly formed dopamine and DOPAC in kidney slices loaded with L-DOPA (50 and 100 microM) was found to be partially dependent on the concentration of sodium in the medium; at 0 mM sodium, the synthesis of dopamine from L-DOPA was found to be half of that occurring at 160 mM sodium. A similar picture could be observed for DOPAC. The fractional rate of accumulation (k; mM sodium-1) at 50 and 100 microM L-DOPA was, respectively, 0.0016 +/- 0.0002 and 0.0016 +/- 0.0005 for dopamine and 0.0018 +/- 0.0002 and 0.0021 +/- 0.0005 for DOPAC.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology and Therapeutics, Faculty of Medicine, Porto, Portugal.
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Pestana
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Fernandes
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D001692:Biological Transport; D003653:Decarboxylation; D004298:Dopamine / Q000096:biosynthesis*; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism*; D007980:Levodopa / Q000378:metabolism / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D012964:Sodium / Q000378:metabolism*
D015102:3,4-Dihydroxyphenylacetic Acid; D007980:Levodopa; D012964:Sodium; D004298:Dopamine