Regulation of Renal LAT2 and 4F2hc Expression by Aldosterone

Abstract

In the spontaneous hypertensive rat, overexpression of the renal Na +-independent L-amino acid transporter LAT2 is organ specific, precedes the onset of hypertension, correlates negatively with plasma aldosterone, and parallels the enhanced ability to take up L-DOPA and form renal dopamine. The present study evaluated the role of aldosterone on transcript and protein abundance of Na +-independent and Na +-dependent amino acid transporters. Na +-independent heterodimeric amino acid transporters LAT1/4F2hc, LAT2/4F2hc and a Na +-dependent transporter ASCT2 transcript and protein abundance was determined in the renal cortex of normotensive Wistar rats chronically treated with aldosterone (1.5 mg), spironolactone (200 mg) or aldosterone plus spironolactone. Aldosterone significantly increased renal cortical LAT2 mRNA levels (45 % increase), with no changes in LAT1, 4F2hc and ASCT2 transcript levels. The effect of aldosterone upon LAT2 mRNA levels was completely prevented by spironolactone. At the protein level, aldosterone treatment did not significantly affect LAT1 and LAT2 expression, but markedly reduced (51 % decrease) the abundance of 4F2hc and the urinary excretion of dopamine and DOPAC. The effect of aldosterone upon 4F2hc protein abundance was not reversed by spironolactone. Increases in renal LAT2 transcript during chronic treatment with aldosterone occur through a spironolactone-sensitive genomic mechanism. This effect parallels with a decrease in LAT2 functionality, resulting from decreases in 4F2hc protein abundance, which appears to be either a non-genomic effect or an indirect effect of aldosterone. The decrease in LAT2 functionality by aldosterone correlates well with the reduction in urinary dopamine.

Renal amino acid transport systems and essential hypertension

“…At the protein level, aldosterone treatment did not significantly affect LAT1 and LAT2 expression, but markedly reduced the abundance of 4F2hc, although reduced levels were not reversed by spironolactone. The decrease in LAT2 functionality (related to the decrease of 4F2hc abundance) correlated well with the reduction in urinary dopamine (96). Taken together, these results suggested that the transcript abundance of AATs is age dependent and can be modulated by aldosterone.…”

“…Attempts were made to determine whether treatment with aldosterone had an effect on L‐DOPA uptake and LAT2 expression in WKY and SHR PTE cells and in Madin‐Darby canine kidney epithelial cells, but no differences were observed in the treatment time frame of the study (unpublished results). On the other hand, 8‐wk‐old normotensive Wistar rats chronically treated for 8 d with aldosterone had increased renal cortical LAT2 mRNA levels with no changes in LAT1, 4F2hc, and ASCT2 transcript levels (96). The effect of aldosterone on LAT2 mRNA levels was completely prevented by spironolactone, a mineralocorticoid receptor antagonist.…”

Characterization of l‐type Amino Acid Transporter 2 from Crucian Carp, Carassius auratus

“…Thus, the regulation of transfer activities by substrates needs to be elucidated in further research. Pinho et al reported that LAT2 and 4Fhc could be downregulated by aldosterone suggesting that LAT2 participates in dopamine metabolism (Amaral et al 2008;Pinho et al 2009). In addition, it has been shown that the function of LAT2 in nervous activity regulation is controlled by steroid hormone.…”