Studies on the role of sodium on the synthesis of dopamine in the rat kidney.
The accumulation of Ldopa, dopamine (DA) and 3,4-dihydroxyphenylacetic (DOPAC) in kidney slices loaded with Ldopa (10-100 microM) was found to be dependent on the concentration of sodium in the medium (0-160 mM). The constant rate of accumulation did not depend on the concentration of Ldopa used and was about 0.0025, 0.0035 and 0.0065 for Ldopa, DA and DOPAC, respectively. In experiments performed in the presence of 120 and 160 mM sodium, but not with 20 mM sodium in the medium, ouabain (500 and 1000 microM) and amphotericin B (10 and 50 micrograms/ml) significantly reduced the accumulation of both DA and DOPAC (6-21 and 29-56% reduction, respectively). Amiloride (5-100 microM) produced an increase in the accumulation of DA and drastically reduced the formation of DOPAC. This effect was found to be due to inhibition of monoamine oxidase. During monoamine oxidase inhibition ethylisopropylamiloride (1, 5 and 10 microM), but not amiloride (10 and 50 microM), increased the accumulation of newly formed DA in kidney slices and reduced the outflow of the amine into the incubation medium. In conclusion, the results presented here show that the formation of DA in kidney slices loaded with Ldopa is dependent on the concentration of sodium in the medium and sensitive to the inhibition of the enzyme Na(+)-K+ adenosine triphosphatase and activation of mechanisms which bypass the tubular transport of sodium.
Soares-da-Silva
P
P
Department of Pharmacology and Therapeutics, Faculty of Medicine, Porto, Portugal.
Fernandes
M H
MH
Pestana
M
M
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism / Q000493:pharmacokinetics; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000666:Amphotericin B / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D004298:Dopamine / Q000096:biosynthesis*; D005110:Extracellular Space / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism; D007700:Kinetics; D007980:Levodopa / Q000378:metabolism / Q000493:pharmacokinetics; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000502:physiology*; D017923:Sodium-Hydrogen Exchangers
D002352:Carrier Proteins; D008996:Monoamine Oxidase Inhibitors; D017923:Sodium-Hydrogen Exchangers; D015102:3,4-Dihydroxyphenylacetic Acid; D007980:Levodopa; D010042:Ouabain; D000584:Amiloride; D000666:Amphotericin B; D012964:Sodium; D004298:Dopamine; C039614:ethylisopropylamiloride