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1 Institute of Pharmacology & Therapeutics, Faculty of Medicine, Porto, Portugal
* To whom correspondence should be addressed. E-mail: psoaresdasilva{at}netcabo.pt.
This study evaluated in SHR and WKY the response to salt loading of the renal dopaminergic system and transcript abundance of Na+-independent (LAT1 and LAT2) and Na+-dependent (ASCT2 and B0AT1) amino acid transporters potentially involved in renal tubular uptake of L-DOPA. Rats were fed normal (NS) or high (HS - 1% saline as drinking water) salt diets for 24 hours. Transcript abundance of amino acid transporters was age dependent, differently regulated in WKY and SHR and responded differently to dietary salt. HS intake similarly increased urinary dopamine in 4-week old SHR and WKY. At 12 weeks of age, HS intake increased urinary dopamine in SHR, but not in WKY. Changes in urinary dopamine paralleled changes in the uptake of L-DOPA in isolated renal tubules from 4- and 12-week old WKY and SHR on NS and HS intake. At 12 weeks of age, HS intake was accompanied by decreases in LAT1 and LAT2 transcript abundance in WKY and SHR. ASCT2 and B0AT1 expression was significantly decreased in both 4- and 12-week old WKY and in 4-week old SHR on HS intake. By contrast, HS intake increased ASCT2 and B0AT1 expression in 12-week old SHR. It is concluded that salt sensitive mechanisms influence LAT1, LAT2, ASCT2 and B0AT1 gene transcription. Differences in urinary dopamine and tubular uptake of L-DOPA between WKY and SHR during HS intake, namely in 12-week old animals, may result from increases in the ASCT2 and B0AT1 mRNA levels and less pronounced decreases in LAT2 expression.
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