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Volume 272, Number 50, Issue of December 12, 1997
pp. 31213-31216
(Received for publication, August 27, 1997, and in revised form, October 8, 1997)
From the Immunohistochemistry of porcine pulmonary artery
endothelial cells (PAEC) with antibodies specific for caveolin,
endothelial nitric-oxide synthase (eNOS), and the arginine transporter
(CAT1) demonstrates that all of these proteins co-localize in plasma membrane caveolae. When incubated with solubilized PAEC plasma membrane
proteins, eNOS-specific antibody immunoprecipitates CAT1-mediated arginine transport. These results document the existence of a caveolar
complex between CAT1 and eNOS in PAEC that provides a mechanism for the
directed delivery of substrate arginine to eNOS. Direct transfer of
extracellular arginine to membrane-bound eNOS accounts for the
"arginine paradox" and explains why caveolar localization of eNOS
is required for optimal nitric oxide production by endothelial
cells.
COMMUNICATION:
A Caveolar Complex between the Cationic Amino Acid
Transporter 1 and Endothelial Nitric-oxide Synthase May Explain the
"Arginine Paradox"
,
Department of Biochemistry and Molecular
Biology and the Center for Structural Biology and the ¶ Department
of Medicine and the Gainesville VA Medical Center, University of
Florida College of Medicine, Gainesville, Florida 32610-0245
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C. B. Cymeryng, S. P. Lotito, C. Colonna, C. Finkielstein, Y. Pomeraniec, N. Grion, L. Gadda, P. Maloberti, and E. J. Podesta Expression of Nitric Oxide Synthases in Rat Adrenal Zona Fasciculata Cells Endocrinology, April 1, 2002; 143(4): 1235 - 1242. [Abstract] [Full Text] [PDF]
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R. Sala, B. M. Rotoli, E. Colla, R. Visigalli, A. Parolari, O. Bussolati, G. C. Gazzola, and V. Dall'Asta Two-way arginine transport in human endothelial cells: TNF-alpha stimulation is restricted to system y+ Am J Physiol Cell Physiol, January 1, 2002; 282(1): C134 - C143. [Abstract] [Full Text] [PDF]
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S. Chowdhary, S. L. Nuttall, J. H. Coote, and J. N. Townend L-Arginine Augments Cardiac Vagal Control in Healthy Human Subjects Hypertension, January 1, 2002; 39(1): 51 - 56. [Abstract] [Full Text] [PDF]
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L. D. Nelin, H. E. Nash, and L. G. Chicoine Cytokine treatment increases arginine metabolism and uptake in bovine pulmonary arterial endothelial cells Am J Physiol Lung Cell Mol Physiol, November 1, 2001; 281(5): L1232 - L1239. [Abstract] [Full Text] [PDF]
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C. E. P. de Figueiredo, B. E. P. da Costa, L. Comerlato, E. Micheli, and E. Barros Low dose L-arginine reduces blood pressure and endothelin-1 production in hypertensive uraemic rats Nephrol. Dial. Transplant., October 1, 2001; 16(10): 2110 - 2111. [Full Text] [PDF]
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M. Jayachandran, T. Hayashi, D. Sumi, A. Iguchi, and V. M. Miller Temporal effects of 17{beta}-estradiol on caveolin-1 mRNA and protein in bovine aortic endothelial cells Am J Physiol Heart Circ Physiol, September 1, 2001; 281(3): H1327 - H1333. [Abstract] [Full Text] [PDF]
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S. Xiao, L. Wagner, J. Mahaney, and C. Baylis Uremic levels of urea inhibit L-arginine transport in cultured endothelial cells Am J Physiol Renal Physiol, June 1, 2001; 280(6): F989 - F995. [Abstract] [Full Text] [PDF]
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 V. Hadkar and R. A. Skidgel Carboxypeptidase D Is Up-Regulated in RAW 264.7 Macrophages and Stimulates Nitric Oxide Synthesis by Cells in Arginine-Free Medium Mol. Pharmacol., April 16, 2001; 59(5): 1324 - 1332. [Abstract] [Full Text]
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S. I. Zharikov, A. A. Sigova, S. Chen, M. R. Bubb, and E. R. Block Cytoskeletal regulation of the L-arginine/NO pathway in pulmonary artery endothelial cells Am J Physiol Lung Cell Mol Physiol, March 1, 2001; 280(3): L465 - L473. [Abstract] [Full Text] [PDF]
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H. Li, S. Brodsky, M. Basco, V. Romanov, D. A. De Angelis, and M. S. Goligorsky Nitric Oxide Attenuates Signal Transduction : Possible Role in Dissociating Caveolin-1 Scaffold Circ. Res., February 2, 2001; 88(2): 229 - 236. [Abstract] [Full Text] [PDF]
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R. Govers and T. J. Rabelink Cellular regulation of endothelial nitric oxide synthase Am J Physiol Renal Physiol, February 1, 2001; 280(2): F193 - F206. [Abstract] [Full Text] [PDF]
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 L. J. Van Winkle Amino Acid Transport Regulation and Early Embryo Development Biol Reprod, January 1, 2001; 64(1): 1 - 12. [Abstract] [Full Text]
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R. E. Rumbaut, J. Wang, and V. H. Huxley Differential effects of L-NAME on rat venular hydraulic conductivity Am J Physiol Heart Circ Physiol, October 1, 2000; 279(4): H2017 - H2023. [Abstract] [Full Text] [PDF]
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J. P. Cooke Does ADMA Cause Endothelial Dysfunction? Arterioscler. Thromb. Vasc. Biol., September 1, 2000; 20(9): 2032 - 2037. [Abstract] [Full Text] [PDF]
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P. T.-Y. Ayuk, C. P. Sibley, P. Donnai, S. D'Souza, and J. D. Glazier Development and polarization of cationic amino acid transporters and regulators in the human placenta Am J Physiol Cell Physiol, June 1, 2000; 278(6): C1162 - C1171. [Abstract] [Full Text] [PDF]
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 F. H. Guo, S. A. A. Comhair, S. Zheng, R. A. Dweik, N. T. Eissa, M. J. Thomassen, W. Calhoun, and S. C. Erzurum Molecular Mechanisms of Increased Nitric Oxide (NO) in Asthma: Evidence for Transcriptional and Post-Translational Regulation of NO Synthesis J. Immunol., June 1, 2000; 164(11): 5970 - 5980. [Abstract] [Full Text] [PDF]
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 C. D. Fike, M. R. Kaplowitz, L. A. Rehorst-Paea, and L. D. Nelin L-Arginine increases nitric oxide production in isolated lungs of chronically hypoxic newborn pigs J Appl Physiol, May 1, 2000; 88(5): 1797 - 1803. [Abstract] [Full Text] [PDF]
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P. G. Lloyd and C. D. Hardin Sorting of metabolic pathway flux by the plasma membrane in cerebrovascular smooth muscle cells Am J Physiol Cell Physiol, April 1, 2000; 278(4): C803 - C811. [Abstract] [Full Text] [PDF]
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L. Eckmann, F. Laurent, T. D. Langford, M. L. Hetsko, J. R. Smith, M. F. Kagnoff, and F. D. Gillin Nitric Oxide Production by Human Intestinal Epithelial Cells and Competition for Arginine as Potential Determinants of Host Defense Against the Lumen-Dwelling Pathogen Giardia lamblia J. Immunol., February 1, 2000; 164(3): 1478 - 1487. [Abstract] [Full Text] [PDF]
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E. I. Closs, J.-S. Scheld, M. Sharafi, and U. Förstermann Substrate Supply for Nitric-Oxide Synthase in Macrophages and Endothelial Cells: Role of Cationic Amino Acid Transporters Mol. Pharmacol., January 1, 2000; 57(1): 68 - 74. [Abstract] [Full Text]
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A. A. Ogonowski, W. H. Kaesemeyer, L. Jin, V. Ganapathy, F. H. Leibach, and R. W. Caldwell Effects of NO donors and synthase agonists on endothelial cell uptake of L-Arg and superoxide production Am J Physiol Cell Physiol, January 1, 2000; 278(1): C136 - C143. [Abstract] [Full Text] [PDF]
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S. I. Zharikov and E. R. Block Association of L-arginine transporters with fodrin: implications for hypoxic inhibition of arginine uptake Am J Physiol Lung Cell Mol Physiol, January 1, 2000; 278(1): L111 - L117. [Abstract] [Full Text] [PDF]
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M. Teubl, K. Groschner, S. D. Kohlwein, B. Mayer, and K. Schmidt Na+/Ca2+ Exchange Facilitates Ca2+-dependent Activation of Endothelial Nitric-oxide Synthase J. Biol. Chem., October 8, 1999; 274(41): 29529 - 29535. [Abstract] [Full Text] [PDF]
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M. Higaki and K. Shimokado Phosphatidylinositol 3-Kinase Is Required for Growth Factor–Induced Amino Acid Uptake by Vascular Smooth Muscle Cells Arterioscler. Thromb. Vasc. Biol., September 1, 1999; 19(9): 2127 - 2132. [Abstract] [Full Text] [PDF]
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J. Leiper and P. Vallance Biological significance of endogenous methylarginines that inhibit nitric oxide synthases Cardiovasc Res, August 15, 1999; 43(3): 542 - 548. [Abstract] [Full Text] [PDF]
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H. Drexler Nitric oxide and coronary endothelial dysfunction in humans Cardiovasc Res, August 15, 1999; 43(3): 572 - 579. [Full Text] [PDF]
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P. Musialek, D. J Paterson, and B. Casadei Changes in extracellular pH mediate the chronotropic responses to L-arginine Cardiovasc Res, August 15, 1999; 43(3): 712 - 720. [Abstract] [Full Text] [PDF]
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