Skip to main content
SpringerLink
Log in

Application of Rapid Dual Tracer Dilution Techniques for the Study of Endothelial Cell Amino Acid Transport in Perfused Microcarrier Cultures

  • Chapter
Cell Membrane Transport

Abstract

Endothelial cells play an important role in the regulation of vascular tone, blood coagulation, platelet aggregation and leukocyte traffic by means of cell surface reactions and secreted mediators such as, prostacyclin (PGI2) and endothelium-derived relaxing factor (EDRF) (Moncada et al., 1976; Furchgott & Zawadzki, 1980; Pearson & Gordon, 1984; Gordon et al., 1986; Gordon & Pearson, 1987; Van de Voorde et al., 1987; Luscher et al., 1990; see reviews Furchgott, 1990 and Moncada & Higgs, 1990). EDRF induces vascular relaxation and inhibits platelet aggregation and adhesion by activating soluble guanylate cyclase in vascular smooth muscle (see Griffiths et al., 1985). Recent studies with perfused aortic endothelial cell microcarrier cultures have now identified EDRF as nitric oxide (Palmer et al., 1987), and suggested that a novel NADPH-dependent enzyme may be involved in the generation of nitric oxide from the terminal nitrogen atom(s) of L-arginine (Palmer & Moncada, 1989).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Allen, L.A. & Gerritsen, M.E. 1986. Regulation of glucose transport in cultured bovine retinal microvessel endothelium by insulin. Exp.o Res. 43: 679–686.

    CAS  Google Scholar 

  • Aisaka, K., Gross, S.S., Griffith, O.W. & Levi, R. 1990. Role of L-arginine in blood pressure regulation. Arch. Intern. Pharmacody. Therap. 305: 226 P.

    Google Scholar 

  • Bassingthwaighte, J.B. & Sparks, H.V. 1986. Indicator dilution estimation of capillary endothelial transport. Ann. Rev. Physiol. 48: 321–334.

    Article  CAS  Google Scholar 

  • Baydoun, A.R., Emery, P.W., Pearson, J.D. & Mann, G.E. (1990). Modulation of intracellular amino acid concentrations in cultured bovine aortic endothelial cells deprived of exogenous L-arginine. J. Physiol. (abstract in press).

    Google Scholar 

  • Betz, A.L., Gilboe, D.D. & Drewes, L.R. 1975. Kinetics of unidirectional leucine transport into brain: effects of isoleucine, valine and anoxia. Am. J. Physiol. 228, 895–900.

    PubMed  CAS  Google Scholar 

  • Betz, A.L., Gibloe, D.D., Yudilevich, D.L. & Drewes, L.R. 1973. Kinetics of unidirectional glucose transport into the isolated dog brain. Am. J. Physiol. 225: 586–592.

    PubMed  CAS  Google Scholar 

  • Betz, A.L. & Goldstein, G.W. 1986. Specialized properties and solute transport in brain capillaries. Ann. Rev. Physiol. 48: 241–250.

    Article  CAS  Google Scholar 

  • Boje, K.M. & Fung, H-L. 1990. Endothelial cell nitric oxide generating enzyme(s) in the bovine aorta: Subcellular location and metabolic characterization. J. Pharmacol. Therap. 253: 20–26.

    CAS  Google Scholar 

  • Boyd, C.A.R. & Parsons, D.S. 1979. Movement of monosaccharides between blood and tissue of vascularly perfused small intestine. J. Physiol. 287: 371–391.

    PubMed  CAS  Google Scholar 

  • Busse, R., Trogisch, G. & Bassenge, E. 1985. The role of endothelium in the control of vascular tone. Basic Res. Cardiol. 80: 475–490.

    Article  PubMed  CAS  Google Scholar 

  • Cancilla, M.D. & Debault, L.E. 1983. Neutral amino acid transport properties of cerebral endothelial cells in vitro. J. Neuropathol. Exp. Neurol, 42: 191–199.

    Article  PubMed  CAS  Google Scholar 

  • Cardelli-Cangiano, P., Fiori, A., Cangiano, C., Barberini, F., Allegra, P., Peresemmpio, V. & Strom, R. 1987. Isolated brain microvessels as in vitro equivalents of the blood-brain barrier: Selective removal by collagenase of the A-system of neutral amino acid transport. J. Neurochem. 49: 1667–1675.

    Article  PubMed  CAS  Google Scholar 

  • Christensen, H.N. & Kilberg, M. 1987. Amino acid transport across the plasma membrane: role of regulation in interorgan flows. In: Amino Acid Transport in Animal Cells, ed. Christensen, H.N. & Kilberg, M, pp. 1–46. Manchester University Press.

    Google Scholar 

  • Corkey, R.F., Corkey, B.E. & Gimbone, M.A. 1981. Hexose transport in normal and SV-40 transformed human endothelial cells in culture. J. Cell Physiol, 106: 425–434.

    Article  PubMed  CAS  Google Scholar 

  • Deneke, S.M., Steiger, V, Fanburg, B.L. 1987. Effect of hyperoxia on glutathione levels and glutamic acid uptake in endothelial cells. J. Appl. Physiol. 63: 1966–1971.

    PubMed  CAS  Google Scholar 

  • Ewadh, M.J.A., Tuball, N. & Rose, F.A. 1988. Transport of L-cystine in human umbilical vein endothelial cells in culture. Bioscience Reports 8: 449–453.

    Article  PubMed  CAS  Google Scholar 

  • Furchgott, R.F. 1990. Studies on the endothelium-dependent vasodilatation and the endothelium-derived relaxing factor. Acta Physiol. Scand. 139: 257–270.

    Article  PubMed  CAS  Google Scholar 

  • Furchgott, R.F. & Zawadski J.V. 1980. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288: 373–376.

    Article  PubMed  CAS  Google Scholar 

  • Garthwaite, J., Charles, G.L. & Chess-Williams, R. 1988. Endothelium-derived relaxing factor release on activation of NMDA receptors suggests role as intracellular messenger in the brain. Nature 336: 385–388.

    Article  PubMed  CAS  Google Scholar 

  • Gerritsen, M.E., Burke, T.M. & Allen, L.A. 1988. Glucose starvation is required for insulin stimulation of glucose uptake and metabolism in cultured microvascular endothelial cells. Microvase. Res. 35: 153–166.

    Article  CAS  Google Scholar 

  • Gerritsen, M.E. & Cheli, C.D. 1983. Arachidonic acid and prostaglandin endoperoxide metabolism in isolated rabbit coronary microvessels and isolated and cultivated coronary microvessel endothelial cells. J. Clin. Invest. 72: 1658–1671.

    Article  PubMed  CAS  Google Scholar 

  • Gillis, C.N. 1986. Pharmacological aspects of metabolic processes in the pulmonary circulation. Ann. Rev. Pharmacol. Toxicol. 26: 183–200.

    Article  CAS  Google Scholar 

  • Gold, M.E., Bush, P.A. & Ignarro, L.J. 1989. Depletion of arterial L-arginine causes reversible tolerance to endothelium-derived relaxation. Biochem. Biophys. Res. Commun. 164: 714–721.

    Article  PubMed  CAS  Google Scholar 

  • Gordon, J.L. & Pearson, J.D. 1987. Biology of the vascular endothelium. In: Haemostasis and Thrombosis, eds. Gordon, J.L. & Pearson, J.D, pp. 303–311, Churchill Livingstone.

    Google Scholar 

  • Gordon, E.L., Pearson, J.D. & Slakey, L.L. 1986. The hydrolysis of extracellular adenine nucleotides by cultured endothelial cells from pig aorta. Feed-forward inhibition of adenosine production at the cell surface. J. Biol. Chem. 261: 15496–15504.

    PubMed  CAS  Google Scholar 

  • Griffiths, T.M., Edwards, D.H., Lewis, M.J. & Henderson, A.H. 1985. Evidence that cyclic guanosine monophosphate (cGMP) mediates endothelium-dependent relaxation. Eur. J. Pharmacol. 112: 195–202.

    Article  Google Scholar 

  • Hibbs, J.B., Taintor, R.R. & Vavrin, Z. 1987. Macrophage cytotoxicity: role of L-arginine deiminase and imino nitrogen oxidation to nitrate. Science 235: 473–476.

    Article  PubMed  CAS  Google Scholar 

  • Ignarro, L.J., Gold, M.E., Buga, G.M., Byrns, R.E., Wood, K.S., Chaudhuri, G. & Frank, G. 1989. Basic polyamino acids rich in arginine, lysine or ornithine cause both enhancement of and refractoriness to formation of endothelium-derived nitric oxide in pulmonary artery and vein. Circ. Res. 64: 315–329.

    Article  PubMed  CAS  Google Scholar 

  • Iyengar, R., Stuehr, D.J. & Marletta, M.A. 1987. Macrophage synthesis of nitrite, nitrate and N-nitrosamines: precursors and role of respiratory burst. Proc. Natl. Acad. Sci. USA 84: 6369–6373.

    Article  PubMed  CAS  Google Scholar 

  • Jaffe, E.A., Nachman, R.L., Becker, C.G. & Minick, C.R. 1973. Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J. Clin. Invest. 52: 2745–2756.

    Article  PubMed  CAS  Google Scholar 

  • King, G.L., Buzney, S.M., Kahn, C.R., Hetu, N., Buchwald, S., Macdonald, S.G. & Rand, L.I. 1983. Differential responsiveness to insulin of endothelial and support cells from micro-and macrovessels. J Clin. Invest. 71: 974–979.

    Article  PubMed  CAS  Google Scholar 

  • Knowles, R.G., Palacios, M., Palmer, R.M.J. & Moncada, S. 1989. Formation of nitric oxide from L-arginine in the central nervous system: A transduction mechanism for stimulation of the soluble guanylate cyclase. Proc. Natl. Acad. Sci. USA 86: 5159–5162.

    Article  PubMed  CAS  Google Scholar 

  • Luckhoff, A., Pohl, U., Mulsch, A. & Busse, R. 1988. Differential role of extra-and intracellular calcium in the release of EDRF and prostacyclin from cultured endothelial cells. Br. J. Pharmacoj. 95: 189–196.

    Article  CAS  Google Scholar 

  • Luscher, T.F., Richard, V., Tschudi, M., Yang, Z. & Boulanger, C. 1990. Endothelial control of vascular tone in large and small coronary arteries. J. Am. Coll. Cardiol. 15: 519–527.

    Article  PubMed  CAS  Google Scholar 

  • Mann, G.E., Munoz, M. & Peran, S. 1986. Fasting and refeeding modulate neutral amino acid transport activity in the basolateral membrane of the rat exocrine pancreatic epithelium: fasting-induced insulin insensitivity. Biochim. Biophys. Acta 862: 119–126.

    Article  PubMed  CAS  Google Scholar 

  • Mann, G.E., Norman, P.S.R. & Smith, I.C.H. 1989a. Amino acid efflux in the isolated perfused rat exocrine pancreas: Trans-stimulation by extracellular amino acids. J. Physiol. 416: 485–502.

    PubMed  CAS  Google Scholar 

  • Mann, G.E., Pearson, J.D., Sheriff, C-J. & Toothill, V.J. 1988. Characterization of amino acid and glucose transport in cultured endothelial cells. Pflugers Arch. 411: R42.

    Article  Google Scholar 

  • Mann, G.E., Pearson, J.D., Sheriff, C-J. & Toothill, V.J. 1989b. Expression of amino acid transport systems in cultured human umbilical vein endothelial cells. J. Physiol. 410: 325–339.

    PubMed  CAS  Google Scholar 

  • Mann, G.E. & Peran, S. 1986. Basolateral amino acid transport systems in the perfused exocrine pancreas: sodium-dependency and kinetic interactions between influx and efflux mechanisms. Biochim. Biophys. Acia 858: 263–274.

    CAS  Google Scholar 

  • Mann, G.E., Sheriff, C-J. & Pearson, J.D. 1990. N°-monomethyl-L-arginine and cationic amino acids inhibit L-arginine transport in perfused microcarrier cultures of aortic endothelial cells. In: Nitric Oxide from L-Arginine: A Bioregulatory System, ed. Moncada, S. & Higgs, E.A., pp. 331–339. Amsterdam: Excerpta Medica.

    Google Scholar 

  • Maruka, C., Spatz, M., Ueki, Y., Nagatsu, I. & Bembray, J. 1984. Cerebrovascular endothelial cell culture: Metabolism and synthesis of 5-hydroxytryptamine. L Neurochem. 43: 316–319.

    Article  Google Scholar 

  • Moncada, S. & Higgs, E.A. 1990. Nitric Oxide from L-Arginine: A Bioregulatory System. pp. 1–512 Excerpta Medica, Amsterdam.

    Google Scholar 

  • Moncada, S., Gryglewski, R.J., Bunting, S. & Vane, J.R. 1976. An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation. Nature 263: 663–665.

    Article  PubMed  CAS  Google Scholar 

  • Myers, P.R., Guerra, R. & Harrison, D.G. 1989. Release of NO and EDRF from cultured bovine aortic endothelial cells. Am. J. Physiol. 256: H1030 - H1037.

    PubMed  CAS  Google Scholar 

  • Needham, L., Cusack, N.J., Pearson, J.D. & Gordon, J.L. 1987. Characteristics of the PZ purinoceptor that mediates prostacyclin production by pig aortic endothelial cells. Eur. J. Ph. rmacol. 134: 199–209.

    CAS  Google Scholar 

  • Norman, P.S.R., Habara, Y. & Mann, G.E. 1989. Paradoxical effects of endogenous and exogenous insulin on amino acid transport activity in the isolated rat pancreas: somatostatin-14 inhibits insulin action. Diabetologia 32: 177–184.

    Article  PubMed  CAS  Google Scholar 

  • Norman, P.S.R. & Mann, G.E. 1987. Ionic dependence of amino acid transport in the exocrine pancreatic epithelium: calcium dependence of insulin action. L Membrane Biol. 96: 153–163.

    Article  CAS  Google Scholar 

  • Palmer, R.M.J. & Moncada, S. 1989. A novel citrulline-forming enzyme implicated in the formation of nitric oxide by vascular endothelial cells. Biochem. Biophys. Res. Comm. 158: 348–353.

    Article  PubMed  CAS  Google Scholar 

  • Palmer, R.M.J., Ferrige, A.G. & Moncada, S. 1987.. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327: 524–526.

    Google Scholar 

  • Palmer, R.M.J., Rees, D.R., Ashton, D.S. & Moncada, S. 1988. L-arginine is the physiological precursor for the formation of nitric oxide in endothelium-dependent relaxation. Biochem. Biophys. Res. Comm. 153: 1251–1256.

    Article  PubMed  CAS  Google Scholar 

  • Pardridge, W.M. 1983. Brain metabolism: a perspective from the blood-brain barrier. Physiol. Rev. 63: a1481–1535.

    Google Scholar 

  • Pearson, J.D. & Gordon, J.L. 1984. Metabolism of serotonin and adenosine. In: Biology of Endothelial Cells, ed. Pearson, J.D. & Gordon, J.L, pp. 330–342. Martinus Nijholt.

    Google Scholar 

  • Peran, S. & McGee, M.P. 1986. Unidirectional flux of phenylalanine into Vero cells. Measurement using paired tracers in perfused cultures. Biochim. Biophys. Acta 856: 231–236.

    Article  PubMed  CAS  Google Scholar 

  • Schmidt, H.H.H.W., Klein, M.M., Niroomand, F. & Bohme, E. 1988. Is arginine a physiological precursor of endothelium-derived nitric oxide? Eur. J. Pharmacol. 148: 293–295.

    Article  PubMed  CAS  Google Scholar 

  • Shepro, D. & Dunham, B. 1986. Endothelial cell metabolism of biogenic amines. Ann. Rev. Physiol. 48, 335–345.

    Article  CAS  Google Scholar 

  • Sheriff, C-J., Pearson, J.D. & Mann, G.E. 1990. Characteristics of amino acid transporters in perfused endothelial cell microcarrier cultures: Role of L-arginine in nitric oxide synthesis. J. Physiol. 423: 6 P.

    Google Scholar 

  • Smith, Q.R., Momma, S., Aoyagi, M. & Rapoport, S.I. 1987. Kinetics of neutral amino acid transport across the blood-brain barrier. J. Neurochem, 49: 1651–1658.

    Article  PubMed  CAS  Google Scholar 

  • Sneddon, J.M., Bearpark, T.M., Galton, S.A. & Vane, J.R. 1990. Transport and metabolism of L-arginine by bovine aortic endothelial cells. In: Nitric Oxide from L-Arginine: A Bioregulatory System, eds. Moncada, S. & E.A. Higgs, pp. 457–461. Amsterdam: Excerpta Medica.

    Google Scholar 

  • Steiger, V., Deneke, S.M. & Fanburg, B.L. 1987. Characterization of glutamic acid uptake by bovine pulmonary arterial endothelial cells. J. Appl. Physiol. 63: 1961–1965.

    PubMed  CAS  Google Scholar 

  • Strum, J.M. & Junod, A.F. 1972. Radioautographic demonstration of 5hydroxytryptamine-[3H] uptake by pulmonary endothelial cells. J. Cell Biol. 54: 456–467.

    Article  PubMed  CAS  Google Scholar 

  • Syrota, A., Girault, M., Pocidalo, J-J. & Yudilevich, D.L. 1982. Endothelial uptake of amino acids, sugars, lipids and prostaglandins in rat lung. Am. J. Physiol. 243: C20 - C26.

    PubMed  CAS  Google Scholar 

  • Takasoto, Y., Momma, S. & Smith, Q.R. 1985. Kinetic analysis of cerebrovascular isoleucine transport from saline and plasma. J. Neurochem. 45: 1013–1020.

    Article  Google Scholar 

  • Thomas, G., Hecker, M. & Ramwell, P.W. 1989. Vascular activity of polycations and basic amino acids: L-arginine does not specifically elicit endothelium-dependent relaxation. Biochem. Biophys. Res. Comm. 158: 177–180.

    Article  PubMed  CAS  Google Scholar 

  • Van de Voorde, J., Vanderstichele, H. & Leusen, I. 1987. Release of endothelium-derived relaxing factor from human umbilical vessels. Circ. Res. 60: 517–522.

    Article  PubMed  Google Scholar 

  • Vinters, H.V., Beck, D.W., Bready, J.V., Maxwell, K., Berliner, J.A., Hart, M.N. & Cancilla, P.A. 1985. Uptake of glucose analogues into cultured cerebral microvessel endothelium. J. Neuropathol. Exp. Neurol. 5: 445–458.

    Article  Google Scholar 

  • Wade, L.A. & Katzman, R. 1975. Synthetic amino acids and the nature of L-DOPA transport at the blood-brain barrier. J. Neurochem. 25: 837–842.

    Article  PubMed  CAS  Google Scholar 

  • Yudilevich, D.L. & Boyd, C.A.R. 1987. Amino Acid Transport in Animal Cells, Manchester: Manchester Univ. Press.

    Google Scholar 

  • Yudilevich, D.L. & Mann, G.E. 1982. Unidirectional uptake of substrates at the blood side of secretory epithelia: stomach, salivary gland and pancreas. Fed. Proc. 41: 3045–3053.

    PubMed  CAS  Google Scholar 

  • Zetter, B.R. 1980. Migration of capillary endothelial cells is stimulated by tumour-derived factors. Nature 285: 41–43.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Biomedical Sciences Division, King’s College London, Campden Hill Road, London, W8 7AH, UK

    G. E. Mann & C-J. Sheriff

  2. Section of Vascular Biology, MRC Clinical Research Centre, Harrow, UK

    V. J. Toothill & J. D. Pearson

Authors
  1. G. E. Mann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C-J. Sheriff
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. V. J. Toothill
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. D. Pearson
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of London, London, UK

    David L. Yudilevich

  2. University of Chile, Santiago, Chile

    Rosa Devés

  3. University of Málaga, Málaga, Spain

    Salvador Perán

  4. The Hebrew University of Jerusalem, Jerusalem, Israel

    Z. Ioav Cabantchik

Rights and permissions

Reprints and permissions

Copyright information

© 1991 Springer Science+Business Media New York

About this chapter

Cite this chapter

Mann, G.E., Sheriff, CJ., Toothill, V.J., Pearson, J.D. (1991). Application of Rapid Dual Tracer Dilution Techniques for the Study of Endothelial Cell Amino Acid Transport in Perfused Microcarrier Cultures. In: Yudilevich, D.L., Devés, R., Perán, S., Cabantchik, Z.I. (eds) Cell Membrane Transport. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-9601-8_23

Download citation

  • DOI: https://doi.org/10.1007/978-1-4757-9601-8_23

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4757-9603-2

  • Online ISBN: 978-1-4757-9601-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation