The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
Glutamine transport by the blood-brain barrier: a possible mechanism for nitrogen removal
Abstract
Glutamine and glutamate transport activities were measured in isolated luminal and abluminal plasma membrane vesicles derived from bovine brain endothelial cells. Facilitative systems for glutamine and glutamate were almost exclusively located in luminal-enriched membranes. The facilitative glutamine carrier was neither sensitive to 2-aminobicyclo(2,2,1)heptane-2-carboxylic acid inhibition nor did it participate in accelerated amino acid exchange; it therefore appeared to be distinct from the neutral amino acid transport system L1. Two Na-dependent glutamine transporters were found in abluminal-enriched membranes: systems A and N. System N accounted for ∼80% of Na-dependent glutamine transport at 100 μM. Abluminal-enriched membranes showed Na-dependent glutamate transport activity. The presence of 1) Na-dependent carriers capable of pumping glutamine and glutamate from brain into endothelial cells, 2) glutaminase within endothelial cells to hydrolyze glutamine to glutamate and ammonia, and 3) facilitative carriers for glutamine and glutamate at the luminal membrane may provide a mechanism for removing nitrogen and nitrogen-rich amino acids from brain.
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“Transporters of neutral and excitatory AA, glycine, taurine, and GABA are enriched abluminally and with high-affinity transport from brain-to-endothelium in a sodium-dependent fashion, and then, these AA are transported across the luminal membrane of the BBB into the blood via low-affinity transporters mediating AA clearance of nitrogen-rich and acidic AA into the circulation (351, 453).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [351]
In the citing paper
“Glutamine is transported into endothelium via sodium-coupled neutral AA transporter 1, 2, 3, and 5 (SNAT1/2/3/5) and then hydrolyzed in endothelium to glutamate via glutaminase, and removed into circulation (351).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [351]
Citations
Cites
Fine structural localization of glutamine synthetase in astrocytes of rat brain
Norenberg, M. D., & Martinez-Hernandez, A. (1979) · Brain Research · doi:10.1016/0006-8993(79)90071-4 · Cited by 1,349
Primary structure and functional characterization of a high-affinity glutamate transporter
Kanai, Y., & Hediger, M. A. (1992) · Nature · doi:10.1038/360467a0 · Cited by 1,337
Cloning and expression of a rat brain L-glutamate transporter
Pines, G., Danbolt, N. C., Bjørås, M., Zhang, Y., Bendahan, A., Eide, L., Koepsell, H., Storm‐Mathisen, J., Seeberg, E. C., & Kanner, B. I. (1992) · Nature · doi:10.1038/360464a0 · Cited by 1,242
Storck, T., Schulte, S., Hofmann, K., & Stoffel, W. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.22.10955 · Cited by 1,193
Biochemistry and physiology of brain ammonia.
Cooper, A. J. L., & Plum, F. (1987) · Physiological Reviews · doi:10.1152/physrev.1987.67.2.440 · Cited by 841
Distinct Mediating Systems for the Transport of Neutral Amino Acids by the Ehrlich Cell
Oxender, D. L., & Christensen, H. N. (1963) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)75327-7 · Cited by 834
Amino acid assignment to one of three blood-brain barrier amino acid carriers
Oldendorf, W., & Szabo, J. (1976) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1976.230.1.94 · Cited by 594
Kinetics of Neutral Amino Acid Transport Across the Blood‐Brain Barrier
Smith, Q. R., Momma, S., Aoyagi, M., & Rapoport, S. I. (1987) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1987.tb01039.x · Cited by 454
Kilberg, M. S., Handlogten, M. E., & Christensen, H. N. (1980) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)85625-9 · Cited by 428
James, J. H., Jeppsson, B. W., Ziparo, V., & Fischer, J. (1979) · The Lancet · doi:10.1016/s0140-6736(79)92119-6 · Cited by 414
The metabolic fate of 13N-labeled ammonia in rat brain.
Cooper, A. J. L., McDonald, J. M., Gelbard, A. S., Gledhill, R. F., & Duffy, T. E. (1979) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)50550-0 · Cited by 353
Curthoys, N. P., & Lowry, O. H. (1973) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)44458-x · Cited by 326
Shaw, P. J., Forrest, V., Ince, P. G., Richardson, J., & Wastell, H. (1995) · Neurodegeneration · doi:10.1006/neur.1995.0026 · Cited by 269
Castillo, J., Dávalos, A., Naveiro, J., & Noya, M. (1996) · Stroke · doi:10.1161/01.str.27.6.1060 · Cited by 258
Glutamine: A Key Substrate for the Splanchnic Bed
Souba, W. W. (1991) · Annual Review of Nutrition · doi:10.1146/annurev.nu.11.070191.001441 · Cited by 247
The Use of N-Methylation to Direct the Route of Mediated Transport of Amino Acids
Christensen, H. N., Oxender, D. L., Liang, M., & Vatz, K. A. (1965) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)97187-5 · Cited by 243
Regional distribution and extracellular levels of amino acids in rat central nervous system
Tossman, U., JONSSON, G., & Ungerstedt, U. (1986) · Acta Physiologica Scandinavica · doi:10.1111/j.1748-1716.1986.tb07938.x · Cited by 209
Recent Advances in Mammalian Amino Acid Transport
Kilberg, M. S., Stevens, B. R., & Novak, D. (1993) · Annual Review of Nutrition · doi:10.1146/annurev.nu.13.070193.001033 · Cited by 192
del Pino, M. M. S., Peterson, D. R., & Hawkins, R. A. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.25.14913 · Cited by 120
Self-citationCangiano, C., Cardelli‐Cangiano, P., James, J. H., Fanelli, F. R., Patrizi, M., Brackett, K. A., Ström, R., & Fischer, J. E. (1983) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)32149-5 · Cited by 110
[38] Distinguishing amino acid transport systems of a given cell or tissue
Christensen, H. N. (1989) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(89)73040-8 · Cited by 110
The identification of neutral amino acid transport systems
Barker, G., & Ellory, J. (1990) · Experimental Physiology · doi:10.1113/expphysiol.1990.sp003382 · Cited by 101
del Pino, M. M. S., Hawkins, R. A., & Peterson, D. R. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.25.14907 · Cited by 92
Self-citationCharacterization and distribution of the neuronal glutamate transporter EAAC1 in rat brain
Velaz-Faircloth, M., McGraw, T. S., alandro, M. S., Fremeau, R. T., Kilberg, M. S., & Anderson, K. J. (1996) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1996.270.1.c67 · Cited by 87
Ammonia selectively stimulates neutral amino acid transport across blood-brain barrier
Mans, A. M., Biebuyck, J. F., & Hawkins, R. A. (1983) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1983.245.1.c74 · Cited by 81
Self-citationLeighton, B., Curi, R., Hussein, A., & Newsholme, E. A. (1987) · FEBS Letters · doi:10.1016/0014-5793(87)81137-7 · Cited by 74
Neutral amino acid transport by the blood-brain barrier. Membrane vesicle studies.
del Pino, M. M. S., Hawkins, R. A., & Peterson, D. R. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)35701-6 · Cited by 73
Self-citationNet amino acid transport between plasma and erythrocytes and perfused dog brain.
Drewes, L. R., Conway, W. P., & Gilboe, D. (1977) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1977.233.4.e320 · Cited by 70
High-affinity transport of glutamate in rat brain microvessels
Hutchison, H. T., Eisenberg, H. M., & Haber, B. (1985) · Experimental Neurology · doi:10.1016/0014-4886(85)90216-x · Cited by 53
Hawkins, R. A., DeJoseph, M. R., & Hawkins, P. A. (1995) · Cell and Tissue Research · doi:10.1007/bf00583389 · Cited by 51
Self-citationSystem A-mediated amino acid transport: metabolic control at the plasma membrane
Kilberg, M. S. (1986) · Trends in Biochemical Sciences · doi:10.1016/0968-0004(86)90138-6 · Cited by 49
Characterization of amino acid transport in human endothelial cells
Bussolati, O., Sala, R., Astorri, A., Rotoli, B. M., Dall’Asta, V., & Gazzola, G. C. (1993) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1993.265.4.c1006 · Cited by 48
Glutamate is transported across the rat blood-brain barrier by a sodium-independent system
Benrabh, H., & Lefauconnier, J.-M. (1996) · Neuroscience Letters · doi:10.1016/0304-3940(96)12635-5 · Cited by 43
Characterization of glutamine transport by liver plasma membrane vesicles
Jacob, R., Rosenthal, N. R., & Barrett, E. J. (1986) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1986.251.5.e509 · Cited by 37
Glutamine transport in human skeletal muscle
Ahmed, A., Maxwell, D. L., Taylor, P. M., & Rennie, M. J. (1993) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1993.264.6.e993 · Cited by 32
Changes in brain metabolism in hepatic encephalopathy
Hawkins, R. A., Mans, A. M., & Biebuyck, J. F. (1987) · Neurochemical Pathology · doi:10.1007/bf02833600 · Cited by 31
Self-citationCharacterization of Na(+)-independent glutamine transport in rat liver
Pacitti, A. J., Inoue, Y., & Souba, W. W. (1993) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1993.265.1.g90 · Cited by 20
Flagged first, then by citations
Research works printed but not linked: 4
- Ahmed A., 1993, Am. J. Physiol., 264, E993
- Drewes L. R., 1977, Am. J. Physiol., 233, E320
- Jacob R., 1986, Am. J. Physiol., 251, E509
- Pacitti A. J., 1993, Am. J. Physiol., 265, G90
Cited by
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Quantitative flux analysis reveals folate-dependent NADPH production
Fan, J., Ye, J., Kamphorst, J. J., Shlomi, T., Thompson, C. B., & Rabinowitz, J. D. (2014) · Nature · doi:10.1038/nature13236 · Cited by 1,114
Munger, J. C., Bennett, B. D., Parikh, A., Feng, X., McArdle, J., RABITZ, H. A., Shenk, T. E., & Rabinowitz, J. D. (2008) · Nature Biotechnology · doi:10.1038/nbt.1500 · Cited by 641
Liu, X., Olszewski, K. L., Zhang, Y., Lim, E. W., Shi, J., Zhang, X., Zhang, J., Lee, H., Koppula, P., Lei, G., et al. (2020) · Nature Cell Biology · doi:10.1038/s41556-020-0496-x · Cited by 603
Fructose-1,6-bisphosphatase opposes renal carcinoma progression
Li, B., Qiu, B., Lee, D. S. M., Walton, Z. E., Ochocki, J. D., Mathew, L. K., Mancuso, A., Gade, T. P. F., Keith, B., Nissim, I., et al. (2014) · Nature · doi:10.1038/nature13557 · Cited by 535
Metadata
- Authors
- Lee, W.-J., Hawkins, R. A., Viña, J. R., & Peterson, D. R.
- Affiliations
- Department of Physiology and Biophysics, Finch University of Health Science/The Chicago Medical School, North Chicago, Illinois 60064-3095; and
- Departamento de Bioquı́mica y Biologı́a Molecular, Facultades de Medicina y Farmacia, Universitat de Valencia, Valencia 46010, Spain
- ORCID
- Hawkins, Richard A.
- Venue
- American Journal of Physiology-Cell Physiology
- Publisher
- American Physiological Society
- Published
- 1998-04-01
- Volume
- 274
- Issue
- 4
- Pages
- C1101-C1107
- ISSN
- 0363-6143 (ISSN-L)
- 1522-1563
- OpenAlex
- W2243408637
- Cited by
- 191
- References
- 37
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 5 · 2023: 2 · 2022: 5 · 2021: 14 · 2020: 7 · 2019: 7 · 2018: 4 · 2017: 9 · 2016: 6 · 2015: 3 · 2014: 7 · 2013: 6 · 2012: 6
- FWCI
- 5.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Cell Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ns031017-03, 5r01ns016389-15)
- National Institute of Neurological Disorders and Stroke (NS-31017, NS16389)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Keywords
- glutamine transport, blood-brain barrier, glutamate uptake, brain endothelial cells, nitrogen removal, glutaminase, sodium-dependent transport, plasma membrane vesicles, system N, system A, ammonia removal, amino acid substitutions
- MeSH terms
- Animals, Biological Transport, Blood-Brain Barrier, Brain, Cattle, Cell Membrane, Endothelium, Vascular, Glutaminase, Glutamine, Nitrogen, Sodium, Glutamic Acid
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