Renal amino acid transport systems and essential hypertension

FASEB Journal

Volumn 27, Issue 8, 2013, Pages 2927-2938

  Pinto, Vanda ^a,b   Pinho, Maria João ^a   Soares Da Silva, Patrício ^a  

^a University of Porto   (Portugal)

^b UNIVERSITY OF PORTO   (Portugal)

Author keywords

Blood pressure; Dopamine; Kidney; Nitric oxide

Indexed keywords

AMINO ACID TRANSPORTER; ARGININE; DOPAMINE; EXCITATORY AMINO ACID TRANSPORTER 3; IMINO ACID; MEMBRANE PROTEIN; MESSENGER RNA; OXIDIZED LOW DENSITY LIPOPROTEIN; PROTEIN SLC1A5; PROTEIN SLC3A2; UNCLASSIFIED DRUG; LEVODOPA;

AGING; BIOAVAILABILITY; BIOTRANSFORMATION; BLOOD BRAIN BARRIER; BLOOD PRESSURE REGULATION; BRUSH BORDER; CATALYSIS; CYSTINURIA; DOPAMINERGIC SYSTEM; ESSENTIAL HYPERTENSION; HARTNUP DISEASE; HUMAN; HYPERAMMONEMIA; HYPERTENSION; KIDNEY BLOOD FLOW; KIDNEY CORTEX; KIDNEY DYSFUNCTION; KIDNEY EPITHELIUM; KIDNEY FUNCTION; KIDNEY MEDULLA; KIDNEY PROXIMAL TUBULE; LYSINURIC PROTEIN INTOLERANCE; MICROSATELLITE MARKER; MUTATIONAL ANALYSIS; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN TRANSPORT; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; REVIEW; RISK ASSESSMENT; SALT LOADING; SMALL INTESTINE; UPREGULATION; ANIMAL; BIOLOGICAL MODEL; KIDNEY; METABOLISM; RAT; SPONTANEOUSLY HYPERTENSIVE RAT;

AMINO ACID TRANSPORT SYSTEMS; ANIMALS; DOPAMINE; HUMANS; HYPERTENSION; KIDNEY; LEVODOPA; MODELS, BIOLOGICAL; RATS; RATS, INBRED SHR;

EID: 84881192710     PISSN: None     EISSN: 15306860     Source Type: Journal    
DOI: 10.1096/fj.12-224998     Document Type: Review

References (98)

1. Kearney, P. M., Whelton, M., Reynolds, K., Muntner, P., Whelton, P. K., and He, J. (2005) Global burden of hypertension: analysis of worldwide data. Lancet 365, 217-223
2. Chobanian, A. V., Bakris, G. L., Black, H. R., Cushman, W. C., Green, L. A., Izzo, J. L., Jr., Jones, D. W., Materson, B. J., Oparil, S., Wright, J. T., Jr., and Roccella, E. J. (2003) The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 289, 2560-2572
3. Taler, S. J. (2008) Secondary causes of hypertension. Primary Care 35, 489-500
4. Levy, D., Garrison, R. J., Savage, D. D., Kannel, W. B., and Castelli, W. P. (1990) Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N. Engl. J. Med. 322, 1561-1566
5. Haddy, F. J. (2006) Role of dietary salt in hypertension. Life Sci. 79, 1585-1592
6. Bianchi, G., Fox, U., Di Francesco, G. F., Giovanetti, A. M., and Pagetti, D. (1974) Blood pressure changes produced by kidney cross-transplantation between spontaneously hypertensive rats and normotensive rats. Clin. Sci. Mol. Med. 47, 435-448
7. Dahl, L. K., Heine, M., and Thompson, K. (1974) Genetic influence of the kidneys on blood pressure. Evidence from chronic renal homografts in rats with opposite predispositions to hypertension. Circ. Res. 40, 94-101
8. Heller, J., Schubert, G., Havlickova, J., and Thurau, K. (1993) The role of the kidney in the development of hypertension: a transplantation study in the Prague hypertensive rat. Pflügers Arch. 425, 208-212
9. Grisk, O., and Rettig, R. (2001) Renal transplantation studies in genetic hypertension. News Physiol. Sci. 16, 262-265
10. Ortiz, P. A., and Garvin, J. L. (2001) Intrarenal transport and vasoactive substances in hypertension. Hypertension 38, 621-624
11. Hussain, T., and Lokhandwala, M. F. (2003) Renal dopamine receptors and hypertension. Exp. Biol. Med. (Maywood) 228, 134-142
12. Gomes, P., and Soares-da-Silva, P. (2008) Dopamine. In Cardiovascular Hormone Systems: From Molecular Mechanisms to Novel Therapeutics (Baden, M., ed) pp. 251-293, Wiley-VCH, Weinheim.
13. Soares-da-Silva, P., and Fernandes, M. H. (1991) A study on the renal synthesis of dopamine in aged rats. Acta Physiol. Scand. 143, 287-293
14. Pestana, M., and Soares-da-Silva, P. (1994) The renal handling of dopamine originating from L-dopa and gamma-glutamyl-Ldopa. Br. J. Pharmacol. 112, 417-422
15. Zeng, C., Zhang, M., Asico, L. D., Eisner, G. M., and Jose, P. A. (2007) The dopaminergic system in hypertension. Clin. Sci. (Lond.) 112, 583-597
16. Zeng, C., Sanada, H., Watanabe, H., Eisner, G. M., Felder, R. A., and Jose, P. A. (2004) Functional genomics of the dopaminergic system in hypertension. Physiol. Genomics 19, 233-246
17. Jose, P. A., Raymond, J. R., Bates, M. D., Aperia, A., Felder, R. A., and Carey, R. M. (1992) The renal dopamine receptors. J. Am. Soc. Nephrol. 2, 1265-1278
18. Zeng, C., and Jose, P. A. (2011) Dopamine receptors: important antihypertensive counterbalance against hypertensive factors. Hypertension 57, 11-17
19. Nishi, A., Bertorello, A. M., and Aperia, A. (1992) High salt diet down-regulates proximal tubule Na+, K(+)-ATPase activity in Dahl salt-resistant but not in Dahl salt-sensitive rats: evidence of defective dopamine regulation. Acta Physiol. Scand. 144, 263-267
20. DeFeo, M. L., Jadhav, A. L., and Lokhandwala, M. F. (1987) Dietary sodium intake and urinary dopamine and sodium excretion during the course of blood pressure development in Dahl salt-sensitive and salt-resistant rats. Clin. Exp. Hypertension A 9, 2049-2060
21. Cowley, A. W., Jr. (1997) Role of the renal medulla in volume and arterial pressure regulation. Am. J. Physiol. 273, R1-15
22. Zhang, Q., Lin, L., Lu, Y., Liu, H., Duan, Y., Zhu, X., Zou, C., Manning, R. D., Jr., and Liu, R. (2013) Interaction between nitric oxide and superoxide in the macula densa in aldosteroneinduced alterations of tubuloglomerular feedback. Am. J. Physiol. Renal Physiol. 304, F326-F332
23. Nakanishi, K., Mattson, D. L., and Cowley, A. W., Jr. (1995) Role of renal medullary blood flow in the development of L-NAME hypertension in rats. Am. J. Physiol. 268, R317-R323
24. Mattson, D. L., Lu, S., Nakanishi, K., Papanek, P. E., and Cowley, A. W., Jr. (1994) Effect of chronic renal medullary nitric oxide inhibition on blood pressure. Am. J. Physiol. 266, H1918-H1926
25. Miyata, N., and Cowley, A. W., Jr. (1999) Renal intramedullary infusion of L-arginine prevents reduction of medullary blood flow and hypertension in Dahl salt-sensitive rats. Hypertension 33, 446-450
26. Verrey, F., Singer, D., Ramadan, T., Vuille-dit-Bille, R. N., Mariotta, L., and Camargo, S. M. (2009) Kidney amino acid transport. Pflügers Arch. 458, 53-60
27. Broer, S. (2008) Amino acid transport across mammalian intestinal and renal epithelia. Physiol. Rev. 88, 249-286
28. Broer, A., Klingel, K., Kowalczuk, S., Rasko, J. E., Cavanaugh, J., and Broer, S. (2004) Molecular cloning of mouse amino acid transport system B0, a neutral amino acid transporter related to Hartnup disorder. J. Biol. Chem. 279, 24467-24476
29. Romeo, E., Dave, M. H., Bacic, D., Ristic, Z., Camargo, S. M., Loffing, J., Wagner, C. A., and Verrey, F. (2006) Luminal kidney and intestine SLC6 amino acid transporters of B0AT-cluster and their tissue distribution in Mus musculus. Am. J. Physiol. Renal Physiol. 290, F376-383
30. Kleta, R., Romeo, E., Ristic, Z., Ohura, T., Stuart, C., Arcos-Burgos, M., Dave, M. H., Wagner, C. A., Camargo, S. R., Inoue, S., Matsuura, N., Helip-Wooley, A., Bockenhauer, D., Warth, R., Bernardini, I., Visser, G., Eggermann, T., Lee, P., Chairoungdua, A., Jutabha, P., Babu, E., Nilwarangkoon, S., Anzai, N., Kanai, Y., Verrey, F., Gahl, W. A., and Koizumi, A. (2004) Mutations in SLC6A19, encoding B0AT1, cause Hartnup disorder. Nat. Genet. 36, 999-1002
31. Singer, D., Camargo, S. M., Huggel, K., Romeo, E., Danilczyk, U., Kuba, K., Chesnov, S., Caron, M. G., Penninger, J. M., and Verrey, F. (2009) Orphan transporter SLC6A18 is renal neutral amino acid transporter B0A T3. J. Biol. Chem. 284, 19953-19960
32. Parks, L. D., and Barfuss, D. W. (2002) Transepithelial transport and metabolism of glycine in S1, S2, and S3 cell types of the rabbit proximal tubule. Am. J. Physiol. Renal Physiol. 283, F1208-F1215
33. Danilczyk, U., Sarao, R., Remy, C., Benabbas, C., Stange, G., Richter, A., Arya, S., Pospisilik, J. A., Singer, D., Camargo, S. M., Makrides, V., Ramadan, T., Verrey, F., Wagner, C. A., and Penninger, J. M. (2006) Essential role for collectrin in renal amino acid transport. Nature 444, 1088-1091
34. Malakauskas, S. M., Quan, H., Fields, T. A., McCall, S. J., Yu, M. J., Kourany, W. M., Frey, C. W., and Le, T. H. (2007) Aminoaciduria and altered renal expression of luminal amino acid transporters in mice lacking novel gene collectrin. Am. J. Physiol. Renal Physiol. 292, F533-F544
35. Singer, D., and Camargo, S. M. (2011) Collectrin and ACE2 in renal and intestinal amino acid transport. Channels (Austin) 5, 410-423
36. Kowalczuk, S., Broer, A., Munzinger, M., Tietze, N., Klingel, K., and Broer, S. (2005) Molecular cloning of the mouse IMINO system: an Na+-and Cl-dependent proline transporter. Biochem. J. 386, 417-422
37. Takanaga, H., Mackenzie, B., Suzuki, Y., and Hediger, M. A. (2005) Identification of mammalian proline transporter SIT1 (SLC6A20) with characteristics of classical system imino. J. Biol. Chem. 280, 8974-8984
38. Wagner, C. A., Lang, F., and Broer, S. (2001) Function and structure of heterodimeric amino acid transporters. Am. J. Physiol. Cell Physiol. 281, C1077-C1093
39. Kanai, Y., and Hediger, M. A. (1992) Primary structure and functional characterization of a high-affinity glutamate transporter. Nature 360, 467-471
40. Hediger, M. A. (1999) Glutamate transporters in kidney and brain. Am. J. Physiol. 277, F487-F492
41. Zerangue, N., and Kavanaugh, M. P. (1996) Flux coupling in a neuronal glutamate transporter. Nature 383, 634-637
42. Verrey, F., Ristic, Z., Romeo, E., Ramadan, T., Makrides, V., Dave, M. H., Wagner, C. A., and Camargo, S. M. (2005) Novel renal amino acid transporters. Annu. Rev. Physiol. 67, 557-572
43. Kanai, Y., Segawa, H., Miyamoto, K., Uchino, H., Takeda, E., and Endou, H. (1998) Expression cloning and characterization of a transporter for large neutral amino acids activated by the heavy chain of 4F2 antigen (CD98). J. Biol. Chem. 273, 23629-23632
44. Prasad, P. D., Wang, H., Huang, W., Kekuda, R., Rajan, D. P., Leibach, F. H., and Ganapathy, V. (1999) Human LAT1, a subunit of system L amino acid transporter: molecular cloning and transport function. Biochem. Biophys. Res. Commun. 255, 283-288
45. Storey, B. T., Fugere, C., Lesieur-Brooks, A., Vaslet, C., and Thompson, N. L. (2005) Adenoviral modulation of the tumorassociated system L amino acid transporter, LAT1, alters amino acid transport, cell growth and 4F2/CD98 expression with cell-type specific effects in cultured hepatic cells. Int. J. Cancer 117, 387-397
46. Soares-da-Silva, P., and Serrao, M. P. (2004) High-and lowaffinity transport of L-leucine and L-DOPA by the hetero amino acid exchangers LAT1 and LAT2 in LLC-PK1 renal cells. Am. J. Physiol. Renal Physiol. 287, F252-F261
47. Pinho, M. J., Serrao, M. P., and Soares-da-Silva, P. (2007) High-salt intake and the renal expression of amino acid transporters in spontaneously hypertensive rats. Am. J. Physiol. Renal Physiol. 292, F1452-1463
48. Nakamura, E., Sato, M., Yang, H., Miyagawa, F., Harasaki, M., Tomita, K., Matsuoka, S., Noma, A., Iwai, K., and Minato, N. (1999) 4F2 (CD98) heavy chain is associated covalently with an amino acid transporter and controls intracellular trafficking and membrane topology of 4F2 heterodimer. J. Biol. Chem. 274, 3009-3016
49. Segawa, H., Fukasawa, Y., Miyamoto, K., Takeda, E., Endou, H., and Kanai, Y. (1999) Identification and functional characterization of a Na+-independent neutral amino acid transporter with broad substrate selectivity. J. Biol. Chem. 274, 19745-19751
50. Pineda, M., Fernandez, E., Torrents, D., Estevez, R., Lopez, C., Camps, M., Lloberas, J., Zorzano, A., and Palacin, M. (1999) Identification of a membrane protein, LAT-2, that Co-expresses with 4F2 heavy chain, an L-type amino acid transport activity with broad specificity for small and large zwitterionic amino acids. J. Biol. Chem. 274, 19738-19744
51. Deves, R., Chavez, P., and Boyd, C. A. (1992) Identification of a new transport system (y+L) in human erythrocytes that recognizes lysine and leucine with high affinity. J. Physiol. 454, 491-501
52. Eleno, N., Deves, R., and Boyd, C. A. (1994) Membrane potential dependence of the kinetics of cationic amino acid transport systems in human placenta. J Physiol. 479(Pt. 2), 291-300
53. Furesz, T. C., and Smith, C. H. (1997) Identification of two leucine-sensitive lysine transport activities in human placental basal membrane. Placenta 18, 649-655
54. Desjeux, J. F., Simell, R. O., Dumontier, A. M., and Perheentupa, J. (1980) Lysine fluxes across the jejunal epithelium in lysinuric protein intolerance. J. Clin. Invest. 65, 1382-1387
55. Rajantie, J., Simell, O., and Perheentupa, J. (1981) Lysinuric protein intolerance. Basolateral transport defect in renal tubuli. J. Clin. Invest. 67, 1078-1082
56. Bauch, C., Forster, N., Loffing-Cueni, D., Summa, V., and Verrey, F. (2003) Functional cooperation of epithelial heteromeric amino acid transporters expressed in madin-darby canine kidney cells. J. Biol. Chem. 278, 1316-1322
57. Dave, M. H., Schulz, N., Zecevic, M., Wagner, C. A., and Verrey, F. (2004) Expression of heteromeric amino acid transporters along the murine intestine. J. Physiol. 558, 597-610
58. Pfeiffer, R., Rossier, G., Spindler, B., Meier, C., Kuhn, L., and Verrey, F. (1999) Amino acid transport of y+L-type by heterodimers of 4F2hc/CD98 and members of the glycoproteinassociated amino acid transporter family. EMBO J. 18, 49-57
59. Torrents, D., Estevez, R., Pineda, M., Fernandez, E., Lloberas, J., Shi, Y. B., Zorzano, A., and Palacin, M. (1998) Identification and characterization of a membrane protein (y+L amino acid transporter-1) that associates with 4F2hc to encode the amino acid transport activity y+L. A candidate gene for lysinuric protein intolerance. J. Biol. Chem. 273, 32437-32445
60. Torrents, D., Mykkanen, J., Pineda, M., Feliubadalo, L., Estevez, R., de Cid, R., Sanjurjo, P., Zorzano, A., Nunes, V., Huoponen, K., Reinikainen, A., Simell, O., Savontaus, M. L., Aula, P., and Palacin, M. (1999) Identification of SLC7A7, encoding y+LAT-1, as the lysinuric protein intolerance gene. Nat. Genet. 21, 293-296
61. Borsani, G., Bassi, M. T., Sperandeo, M. P., De Grandi, A., Buoninconti, A., Riboni, M., Manzoni, M., Incerti, B., Pepe, A., Andria, G., Ballabio, A., and Sebastio, G. (1999) SLC7A7, encoding a putative permease-related protein, is mutated in patients with lysinuric protein intolerance. Nat. Genet. 21, 297-301
62. Tanner, L. M., Nanto-Salonen, K., Venetoklis, J., Kotilainen, S., Niinikoski, H., Huoponen, K., and Simell, O. (2007) Nutrient intake in lysinuric protein intolerance. J. Inherit. Metab. Dis. 30, 716-721
63. Utsunomiya-Tate, N., Endou, H., and Kanai, Y. (1996) Cloning and functional characterization of a system ASC-like Na+-dependent neutral amino acid transporter. J. Biol. Chem. 271, 14883-14890
64. Avissar, N. E., Ryan, C. K., Ganapathy, V., and Sax, H. C. (2001) Na(+)-dependent neutral amino acid transporter ATB(0) is a rabbit epithelial cell brush-border protein. Am. J. Physiol. Cell Physiol. 281, C963-C971
65. Fuchs, B. C., and Bode, B. P. (2005) Amino acid transporters ASCT2 and LAT1 in cancer: partners in crime? Semin. Cancer Biol. 15, 254-266
66. Palmer, R. M., Rees, D. D., Ashton, D. S., and Moncada, S. (1988) L-arginine is the physiological precursor for the formation of nitric oxide in endothelium-dependent relaxation. Biochem. Biophys. Res. Commun. 153, 1251-1256
67. Morris, S. M., Jr. (2009) Recent advances in arginine metabolism: roles and regulation of the arginases. Br. J. Pharmacol. 157, 922-930
68. Kakoki, M., Wang, W., and Mattson, D. L. (2002) Cationic amino acid transport in the renal medulla and blood pressure regulation. Hypertension 39, 287-292
69. Pinho, M. J., Gomes, P., Serrao, M. P., Bonifacio, M. J., and Soares-da-Silva, P. (2003) Organ-specific overexpression of renal LAT2 and enhanced tubular L-DOPA uptake precede the onset of hypertension. Hypertension 42, 613-618
70. Pinho, M. J., Serrao, M. P., Gomes, P., Hopfer, U., Jose, P. A., and Soares-da-Silva, P. (2004) Over-expression of renal LAT1 and LAT2 and enhanced L-DOPA uptake in SHR immortalized renal proximal tubular cells. Kidney Int. 66, 216-226
71. Pinho, M. J., Serrao, M. P., Jose, P. A., and Soares-da-Silva, P. (2007) Organ specific underexpression renal of Na+-dependent B0AT1 in the SHR correlates positively with overexpression of NHE3 and salt intake. Mol. Cell. Biochem. 306, 9-18
72. Pinho, M. J., Pinto, V., Serrao, M. P., Jose, P. A., and Soares-da-Silva, P. (2007) Underexpression of the Na+-dependent neutral amino acid transporter ASCT2 in the spontaneously hypertensive rat kidney. Am. J. Physiol. 293, R538-547
73. Lo, M., Liu, K. L., Clemitson, J. R., Sassard, J., and Samani, N. J. (2002) Chromosome 1 blood pressure QTL region influences renal function curve and salt sensitivity in SHR. Physiol. Genomics 8, 15-21
74. Quan, H., Athirakul, K., Wetsel, W. C., Torres, G. E., Stevens, R., Chen, Y. T., Coffman, T. M., and Caron, M. G. (2004) Hypertension and impaired glycine handling in mice lacking the orphan transporter X T2. Mol. Cell. Biol. 24, 4166-4173
75. Eslami, B., Kinboshi, M., Inoue, S., Harada, K., Inoue, K., and Koizumi, A. (2006) A nonsense polymorphism (Y319X) of the solute carrier family 6 member 18 (SLC6A18) gene is not associated with hypertension and blood pressure in Japanese. Tohoku J. Exp. Med. 208, 25-31
76. Yoon, Y. H., Seol, S. Y., Heo, J., Chung, C. N., Park, I. H., and Leem, S. H. (2008) Analysis of VNTRs in the solute carrier family 6, member 18 (SLC6A18) and lack of association with hypertension. DNA Cell Biol. 27, 559-567
77. Seol, S. Y., Lee, S. Y., Kim, Y. D., Do, E. J., Kwon, J. A., Kim, S. I., Chu, I. S., and Leem, S. H. (2008) Minisatellite polymorphisms of the SLC6A19: susceptibility in hypertension. Biochem. Biophys. Res. Commun. 374, 714-719
78. Wu, F., Cholewa, B., and Mattson, D. L. (2000) Characterization of L-arginine transporters in rat renal inner medullary collecting duct. Am. J. Physiol. 278, R1506-R1512
79. Rajapakse, N. W., Kuruppu, S., Hanchapola, I., Venardos, K., Mattson, D. L., Smith, A. I., Kaye, D. M., and Evans, R. G. (2012) Evidence that renal arginine transport is impaired in spontaneously hypertensive rats. Am. J. Physiol. Renal Physiol. 302, F1554-F1562
80. Zheng, H. Z., Wang, X. H., Liu, X. Y., Tang, C. S., and Liu, N. K. (2000) The changes in the heart and erythrocyte L-arginine transport of spontaneously hypertensive rats. Sheng Li Xue Bao 52, 323-328
81. Schlaich, M. P., Parnell, M. M., Ahlers, B. A., Finch, S., Marshall, T., Zhang, W. Z., and Kaye, D. M. (2004) Impaired L-arginine transport and endothelial function in hypertensive and genetically predisposed normotensive subjects. Circulation 110, 3680-3686
82. Mendes Ribeiro, A. C., and Brunini, T. M. (2004) L-arginine transport in disease. Curr. Med. Chem. Cardiovasc. Hematol. Agents 2, 123-131
83. Racasan, S., Braam, B., van der Giezen, D. M., Goldschmeding, R., Boer, P., Koomans, H. A., and Joles, J. A. (2004) Perinatal L-arginine and antioxidant supplements reduce adult blood pressure in spontaneously hypertensive rats. Hypertension 44, 83-88
84. Fleck, C., Schwertfeger, M., and Taylor, P. M. (2003) Regulation of renal amino acid (AA) transport by hormones, drugs and xenobiotics-a review. Amino Acids 24, 347-374
85. Agostinho, P., Duarte, C. B., and Oliveira, C. R. (1997) Impairment of excitatory amino acid transporter activity by oxidative stress conditions in retinal cells: effect of antioxidants. FASEB J. 11, 154-163
86. Conrad, M., and Sato, H. (2012) The oxidative stress-inducible cystine/glutamate antiporter, system xc +: cystine supplier and beyond. Amino Acids 42, 231-246
87. Uchiyama, T., Matsuda, Y., Wada, M., Takahashi, S., and Fujita, T. (2005) Functional regulation of Na+-dependent neutral amino acid transporter ASCT2 by S-nitrosothiols and nitric oxide in Caco-2 cells. FEBS Lett. 579, 2499-2506
88. Silva, E., and Soares-da-Silva, P. (2007) Reactive oxygen species and the regulation of renal Na+-K+-ATPase in opossum kidney cells. Am. J. Physiol. 293, R1764-R1770
89. Simao, S., Fraga, S., Jose, P. A., and Soares-da-Silva, P. (2008) Oxidative stress and alpha1-adrenoceptor-mediated stimulation of the Cl-/HCO3-exchanger in immortalized SHR proximal tubular epithelial cells. Br. J. Pharmacol. 153, 1445-1455
90. Simao, S., Fraga, S., Jose, P. A., and Soares-da-Silva, P. (2008) Oxidative stress plays a permissive role in alpha2-adrenoceptormediated events in immortalized SHR proximal tubular epithelial cells. Mol. Cell. Biochem. 315, 31-39
91. Pedrosa, R., Villar, V. A., Pascua, A. M., Simao, S., Hopfer, U., Jose, P. A., and Soares-da-Silva, P. (2008) H2O2 stimulation of the Cl-/HCO3-exchanger by angiotensin II and angiotensin II type 1 receptor distribution in membrane microdomains. Hypertension 51, 1332-1338
92. Pinto, V., Pinho, M. J., Jose, P. A., and Soares-da-Silva, P. (2010) Role of H(2)O(2) on the kinetics of low-affinity high-capacity Na(+)-dependent alanine transport in SHR proximal tubular epithelial cells. Biochem. Biophys. Res. Commun. 398, 553-558
93. Simao, S., Gomes, P., Pinho, M. J., and Soares-da-Silva, P. (2011) H2 O2 stimulates Cl-/HCO 3-exchanger activity through oxidation of thiol groups in immortalized SHR renal proximal tubular epithelial cells. J. Cell. Biochem. 112, 3660-3665
94. Yasuhara, A., Wada, J., Malakauskas, S. M., Zhang, Y., Eguchi, J., Nakatsuka, A., Murakami, K., Kanzaki, M., Teshigawara, S., Yamagata, K., Le, T. H., and Makino, H. (2008) Collectrin is involved in the development of salt-sensitive hypertension by facilitating the membrane trafficking of apical membrane proteins via interaction with soluble N-ethylmaleiamide-sensitive factor attachment protein receptor complex. Circulation 118, 2146-2155
95. Spindler, B., Mastroberardino, L., Custer, M., and Verrey, F. (1997) Characterization of early aldosterone-induced RNAs identified in A6 kidney epithelia. Pflügers Arch. 434, 323-331
96. Pinho, M., Amaral, J., Pinto, V., Serrão, M., and Soares-da-Silva, P. (2009) Regulation of renal LAT2 and 4F2hc expression by aldosterone. J. Epithelial Biol. Pharmacol. 2, 36-43
97. Melk, A., Mansfield, E. S., Hsieh, S. C., Hernandez-Boussard, T., Grimm, P., Rayner, D. C., Halloran, P. F., and Sarwal, M. M. (2005) Transcriptional analysis of the molecular basis of human kidney aging using cDNA microarray profiling. Kidney Int. 68, 2667-2679
98. Pinto, V., Amaral, J., Silva, E., Simao, S., Cabral, J. M., Afonso, J., Serrao, M. P., Gomes, P., Pinho, M. J., and Soares-da-Silva, P. (2011) Age-related changes in the renal dopaminergic system and expression of renal amino acid transporters in WKY and SHR rats. Mech. Ageing Dev. 132, 298-304