Genomic regulation of intestinal amino acid transporters by aldosterone.
Overexpression of renal LAT2, a Na+ -independent L-amino acid transporter, in spontaneous hypertensive rats (SHR) is organ specific and precedes the onset of hypertension (Pinho et al., Hypertension, 42:613-618, 2003). However, the expression of LAT2 correlates negatively with plasma aldosterone levels after high sodium intake (Pinho et al., Am J Physiol Ren Physiol 292:F1452-F1463, 2007). The present study evaluated the expression of Na+ -independent LAT1, LAT2, and 4F2hc and Na+ -dependent ASCT2 amino acid transporters in the intestine of normotensive Wistar rats chronically treated with aldosterone. In conditions of high salt intake, to keep endogenous aldosterone to a minimum, rats were implanted with aldosterone or spironolactone tablets. In aldosterone-treated and aldosterone + spironolactone-treated rats, aldosterone plasma levels were increased by fourfold. At the protein level, aldosterone treatment significantly increased LAT1 (62%), LAT2 (49%), 4F2hc (48%), and ASCT2 (65%) expression. The effect of aldosterone upon LAT1, LAT2, 4F2hc, and ASCT2 protein abundance was completely reversed by spironolactone. Aldosterone significantly increased intestinal LAT2 and 4F2hc mRNA levels (27% and 35% increase, respectively), with no changes in LAT1 and ASCT2 transcript levels. In conclusion, increases in intestinal Na+ -independent LAT1 and LAT2 and Na+ -dependent ASCT2 transcript and protein abundance during chronic treatment with aldosterone occur through a spironolactone-sensitive genomic mechanism.
Amaral
João S
JS
Faculty of Medicine, Institute of Pharmacology and Therapeutics, 4200-319 Porto, Portugal.
Pinho
Maria João
MJ
Soares-da-Silva
Patrício
P
D000450:Aldosterone / Q000097:blood / Q000494:pharmacology*; D026905:Amino Acid Transport Systems / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D016678:Genome / Q000187:drug effects / Q000235:genetics*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects*; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008297:Male; D009994:Osmolar Concentration; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000097:blood; D017673:Sodium Chloride, Dietary / Q000494:pharmacology; D013148:Spironolactone / Q000494:pharmacology
D026905:Amino Acid Transport Systems; D012333:RNA, Messenger; D017673:Sodium Chloride, Dietary; D013148:Spironolactone; D000450:Aldosterone; D012964:Sodium