Amaral João S, Pinho Maria João, Soares-da-Silva Patrício
Faculty of Medicine, Institute of Pharmacology and Therapeutics, 4200-319 Porto, Portugal.
Mol Cell Biochem. 2008 Jun;313(1-2):1-10. doi: 10.1007/s11010-008-9735-3. Epub 2008 Mar 18.
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.
钠非依赖性L-氨基酸转运体肾LAT2在自发性高血压大鼠（SHR）中过表达具有器官特异性，且先于高血压发作（皮尼奥等人，《高血压》，42:613 - 618，2003年）。然而，高钠摄入后LAT2的表达与血浆醛固酮水平呈负相关（皮尼奥等人，《美国生理学杂志：肾脏生理学》292:F1452 - F1463，2007年）。本研究评估了醛固酮长期治疗的正常血压Wistar大鼠肠道中钠非依赖性LAT1、LAT2和4F2hc以及钠依赖性ASCT2氨基酸转运体的表达。在高盐摄入条件下，为使内源性醛固酮降至最低，给大鼠植入醛固酮或螺内酯片。在醛固酮治疗组和醛固酮 + 螺内酯治疗组大鼠中，血浆醛固酮水平增加了四倍。在蛋白质水平上，醛固酮治疗显著增加了LAT1（62%）、LAT2（49%）、4F2hc（48%）和ASCT2（65%）的表达。螺内酯完全逆转了醛固酮对LAT1、LAT2、4F2hc和ASCT2蛋白丰度的影响。醛固酮显著增加肠道LAT2和4F2hc mRNA水平（分别增加27%和35%），而LAT1和ASCT2转录水平无变化。总之，醛固酮长期治疗期间肠道中钠非依赖性LAT1和LAT2以及钠依赖性ASCT2转录本和蛋白丰度的增加是通过螺内酯敏感的基因组机制实现的。
