The Processing and Transport of Peptide Hormones Across Endothelial Cell Barriers

  • Donald P. Bottaro
  • George L. King


Transcytosis is the transcellular transport of substances from one side of the cell to the other side within vesicles. Transported substances are taken up by endocytosis at one plasma membrane surface and are released via exocytosis at a different surface, which allows these substances to bypass intercellular junctions. The term was originally proposed for vesicular transport across endothelial cells (1), where the transcellular route is the main route of vesicle traffic, especially in capillaries with a continuous endothelium like those of skeletal and cardiac muscle, and brain. Transcytosis is also observed in many other types of cells, such as the transport of IgG from the lumen of the intestine to the perivascular space in the newborn rat (2), and the transport of IgA from the vascular front to the bile capillary front by hepatocytes (3,4).


Endothelial Cell Insulin Receptor Phorbol Ester Aortic Endothelial Cell Insulin Binding 
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  1. 1.
    Simionescu, N. 1979. The microvascular endothelium: Segmental differentiations, transcytosis, selective distribution of anionic sites. Adv Inflammation Res 1: 64–70.Google Scholar
  2. 2.
    Rodewald, R. 1980. Distribution of immunoglobulin G receptors in the small intestine of the young rat. J Cell Biol 85: 18–32.PubMedCrossRefGoogle Scholar
  3. 3.
    Renston, R.H., A.L. Jones, W.D. Christiansen, G. Hradeck, and B.J. Underdown. 1980. Evidence for a vesicular transport mechanism in hepatocytes for biliary secretion of immunoglobulin A. Science 208: 1276–1278.PubMedCrossRefGoogle Scholar
  4. 4.
    Nagura, H., P.K. Nakame, and W.R. Brown. 1979. Translocation of dimeric IgA through neoplastic colon cells in vitro. J Immunol 123: 2359–2368.Google Scholar
  5. 5.
    Shea, S.M., M.J. Karnovsky, and W.H. Bossert. 1969. Vesicle transport across endothelium: Simulation of a diffusion model. J Theoret Biol 24: 30–42.CrossRefGoogle Scholar
  6. 6.
    Casley-Smith, J.R. 1969. The dimensions and numbers of small vesicles in cells, endothelial and mesothelial and the significance of these for endothelial permeability. J Microsc 90: 251–269.PubMedCrossRefGoogle Scholar
  7. 7.
    Palade, G.E., M. Simionescu, and N. Simionescu. 1979. Structural aspects of the permeability of the microvascular endothelium. Acta Physiol Scand Suppl 463: 11–32.PubMedGoogle Scholar
  8. 8.
    Vasile, E., M. Simionescu, and N. Simionescu. 1983. Visualization of the binding, endocytosis, and transcytosis of low-density lipoprotein in the arterial endothelium in situ. J Cell Biol 96: 1677–1689.PubMedCrossRefGoogle Scholar
  9. 9.
    King, G.L., and S.M. Johnson. 1985. Receptor-mediated transport of insulin across endothelial cells. Science 227: 1583–1586.PubMedCrossRefGoogle Scholar
  10. 10.
    Ghitescu, L., A. Fixman, M. Simionescu, and N. Simionescu. 1986. Specific binding sites for albumin restricted to plasma lemmal vesicles of continuous capillary endothelium: Receptor-mediated transcytosis. J Cell Biol 102: 1304–1311.PubMedCrossRefGoogle Scholar
  11. 11.
    Marshall, S. 1985. Kinetics of insulin receptor internalization and recycling in adipocytes. Shunting of receptors to a degradative pathway by inhibitors of recycling. J Biol Chem 260: 4136–4144.PubMedGoogle Scholar
  12. 12.
    Malaisse, W.J. 1984.. Stimulus-secretion coupling in the pancreatic B-cell. Experientia 40: 1025–1164.Google Scholar
  13. 13.
    Goldstein, J.L., R.G.W. Anderson, and M.S. Brown. 1979. Coated pits, coated vesicles, and receptor-mediated endocytosis. Nature (Lond) 5715: 679–685.CrossRefGoogle Scholar
  14. 14.
    King, G.L. Unpublished observations.Google Scholar
  15. 15.
    Mostov, K.E., and D.L. Deitcher. 1986. Polymeric immunoglobulin receptor expressed in MDCK cells transcytoses IgA. Cell 46: 613–621.PubMedCrossRefGoogle Scholar
  16. 16.
    Von Bondsdorff, C.H., S.D. Fuller, and K. Simons. 1985. Apical and basolateral endocytosis in Madin-Darby canine kidney (MDCK) cells grown on nitrocellulose filters. EMBO J 4: 2781–2792.Google Scholar
  17. 17.
    Pesonen, M., W. Ansorge, and K. Simons. 1984. Transcytosis of the G protein of vesicular stomatitis virus after implantation into the apical plasma membrane of Madin-Darby canine kidney cells. I Involvement of endosomes and lysosomes. J Cell Biol 99: 796–802.PubMedCrossRefGoogle Scholar
  18. 18.
    Herzog, V. 1983. Preparation of inside-out thyroid follicles for studies on transcellular transport (transcytosis). Methods Enzymol 98: 447–458.PubMedCrossRefGoogle Scholar
  19. 19.
    Herzog, V. 1983. Transcytosis in thyroid follicle cells. J Cell Biol 97: 607–617.PubMedCrossRefGoogle Scholar
  20. 20.
    Bar, R.S., M.L. Peacock, R.G. Spanheimer, R. Veenstra and J.C. Hoak. 1980. Differential binding of insulin to human arterial and venous endothelial cells in primary culture. Diabetes 29: 991–995.PubMedCrossRefGoogle Scholar
  21. 21.
    Frank, H.J.L., and W.M. Pardridge. 1981. A direct in vitro demonstration of insulin binding to isolated brain microvessels. Diabetes 30: 757–761.PubMedCrossRefGoogle Scholar
  22. 22.
    King, G.L., S.M. Buzney, C.R. Kahn, N. Hetu, S. Buchwald, S.G. MacDonald, and L.I. Rand. 1983. Differential responsiveness to insulin of endothelial and support cells from micro-and macrovessels. J Clin Invest 71: 974–979.PubMedCrossRefGoogle Scholar
  23. 23.
    Bar, R.S., and M. Boes. 1984. Distinct receptors for IGF-I, IGF-II, and insulin are present on bovine capillary endothelial cells and large vessel endothelial cells. Biochem Biophys Res Commun 124: 203–209.PubMedCrossRefGoogle Scholar
  24. 24.
    King, G.L., A.D. Goodman, S. Buzney, A. Moses, and C.R. Kahn. 1985. Receptors and growth-promoting effects of insulin and insulin-like growth factors on cells from bovine retinal capillaries and aorta. J Clin Invest 75: 1028–1036.PubMedCrossRefGoogle Scholar
  25. 25.
    Jialal, I., M. Crettaz, H.L. Hachiya, C.R. Kahn, A.C. Moses, S.M. Buzney, and G.L. King. 1985. Characterization of the receptors for insulin and the insulin-like growth factors on micro- and macrovascular tissues. Endocrinology 117: 1222–1229.PubMedCrossRefGoogle Scholar
  26. 26.
    Kasuga, M., F.A. Karlsson, and C.R. Kahn. 1982. Insulin stimulates the phosphorylation of the 95,000-dalton subunit of its own receptor. Science 215: 185–187.PubMedCrossRefGoogle Scholar
  27. 27.
    White, M.F., R. Maron, and C.R. Kahn. 1985. Insulin rapidly stimulates tyrosine phosphorylation of a Mr-185,000 protein in intact cells. Nature 318: 183–186.PubMedCrossRefGoogle Scholar
  28. 28.
    Kasuga, M., E. Van Obberghen, S.P. Nissley, and M.M. Rechler. 1981. Demonstration of two subtypes of insulin-like growth factor receptors by affinity cross-linking. J Biol Chem 256: 5305–5308.PubMedGoogle Scholar
  29. 29.
    Massague, J., and M. Czech. 1982. The subunit structures of two distinct receptors for insulin-like growth factors I and II and their relationship to the insulin receptor. J Biol Chem 257: 5038–5045.PubMedGoogle Scholar
  30. 30.
    Bar, R.S., A. DeRose, A. Sandra, M.L. Peacock, and W.G. Owen. 1983. Insulin binding to microvascular endothelium: A kinetic and morphometric analysis. Am J Physiol 244: E447–E452.PubMedGoogle Scholar
  31. 31.
    Banskota, N.K., J.L. Carpentier, and G.L. King. 1986. Processing and release of insulin and insulin-like growth factor I by macro-and microvascular endothelial cells. Endocrinology 119: 1904–1913.PubMedCrossRefGoogle Scholar
  32. 32.
    Maxfield, F. 1982. Weak bases and ionophores rapidly and reversibly raise the pH of endocytic vesicles in cultured mouse fibroblasts. J Clin Biol 95: 676–681.CrossRefGoogle Scholar
  33. 33.
    Marshall, S. 1985. Dual pathways for the intracellular processing of insulin. Relationship between retroendocytosis of intact hormone and the recycling of insulin receptors. J Biol Chem 260: 13524–13531.PubMedGoogle Scholar
  34. 34.
    Hachiya, H.L., J.L. Carpentier, and G.L. King. 1986. Comparative studies on insulin-like growth factor-II and insulin processing by vascular endothelial cells. Diabetes 35: 1065–1072.PubMedCrossRefGoogle Scholar
  35. 35.
    Hachiya, H.L., S. Takayama, M.F. White, and G.L. King. 1987. Regulation of insulin receptor internalization in vascular endothelial cells by insulin and phorbol ester. J Biol Chem In press.Google Scholar
  36. 36.
    Klausner, R.D., J. Harford, and J. Van Renswoude. 1984. Rapid internalization of the transferrin receptor in K562 cells is triggered by ligand binding or treatment with a phorbol ester. Proc Natl Acad Sci USA 81: 3005–3009.PubMedCrossRefGoogle Scholar
  37. 37.
    Lee, L.S., and I.B. Weinstein. 1978. Tumor-promoting phorbol esters inhibit binding of epidermal growth factor to cellular receptors. Science 202: 313–315.PubMedCrossRefGoogle Scholar
  38. 38.
    Magnum, B.E., I.M. Matrisian, and G.T. Bowden. 1980. Epidermal growth factor. Ability of tumor promotor to alter its degradation, receptor affinity and receptor number. J Biol Chem 255: 6373–6381.Google Scholar
  39. 39.
    Beguinot, L., J.A. Hanover, S. Ito, N.D. Richert, M.C. Willingham, and J. Pastan. 1985. Phorbol esters induce transient internalization without degradation of unoccupied epidermal growth factor receptors. Proc Natl Acad Sci USA 82: 2774–2778.PubMedCrossRefGoogle Scholar
  40. 40.
    Kelleher, D.J., J.E. Pessin, A.E. Rusho, and G.L. Johnson. 1984. Phorbol ester induces desensitization of adenylate cyclase and phosphorylation of the ß-adrenergic receptor in turkey erythrocytes. Proc Natl Acad Sci USA 81: 4316–4320.PubMedCrossRefGoogle Scholar
  41. 41.
    Nambi, P., J.R. Peters, D.R. Silbey, and R.J. Lefkowitz. 1985. Desensitization of the turkey erythrocyte ß-adrenergic receptor in a cell-free system. Evidence that multiple protein kinases can phosphorylate and desensitize the receptor. J Biol Chem 260: 2165–2171.PubMedGoogle Scholar
  42. 42.
    Bottaro, D.P., and G.L. King. 1987. Insulin receptor recycling in microvessel endothelial cells and its regulation by insulin and phorbol ester. Manuscript in preparation.Google Scholar
  43. 43.
    Haskell, J.F., E. Meezan, and D.J. Pillion. 1984. Identification and characterization of the insulin receptor of bovine retinal microvessels. Endocrinology 115: 698–704.PubMedCrossRefGoogle Scholar
  44. 44.
    Haskell, J.F., E. Meezan, and D.J. Pillion. 1985. Identification of the insulin receptor of cerebral microvessels. Am J Physiol 248: E115–E125.PubMedGoogle Scholar
  45. 45.
    Pardridge, W.M. 1986. Receptor-mediated peptide transport through the blood-brain barrier. Endocrine Rev 7: 314–330.CrossRefGoogle Scholar
  46. 46.
    Frank, H.J.L., W.M. Pardridge, W.L. Morris, R.G. Rosenfeld, and T.B. Choi. 1986. Binding and internalization of insulin and insulin-like growth factors by isolated brain microvessels. Diabetes 35: 654–661.PubMedCrossRefGoogle Scholar
  47. 47.
    Wallum, B.J., G.J. Taborsky, D. Porte, D.P. Figlewicz, L. Jacobson, J.C. Beard, W.K. Ward, and D. Dorsa. 1987. Cerebrospinal fluid insulin levels increase during intravenous insulin infusions in man. J Clin Endocrinol Metab 64: 190–194.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • Donald P. Bottaro
    • 1
  • George L. King
    • 1
  1. 1.Research Division, Joslin Diabetes Center, Department of Medicine, Brigham and Women’s HospitalHarvard Medical SchoolBostonUSA

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