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Epidermal growth factor does not cross the blood-brain barrier

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Summary

To measure the passage of epidermal growth factor (EGF) through the blood-brain barrier (BBB) 125Ilabeled EGF was injected intravenously into adult rats. The distribution of 125I-EGF in the blood and cerebrospinal fluid (CSF) was determined over a time period of several hours. Between 2 to 6 h a stable distribution of intact 125IEGF in CSF was measured to be approximately 1/500 of the blood-borne EGF, an equilibrium value below those obtained by other investigators for BBB-impermeable compounds, such as inulin and bovine serum albumin. Our data indicate that 125I-EGF, although clearly detectable in the CSF, does not cross the BBB at a higher rate or in higher quantities than would be expected from its molecular size.

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Abbreviations

BBB :

blood-brain barrier

BSA :

bovine serum albumin

CSF :

cerebrospinal fluid

EGF :

epidermal growth factor

PBS :

phosphate-buffered saline

SDS-PAGE :

sodium dodecylsulfate polyacrylamide gel electrophoresis

TBS :

Tris-buffered saline

References

  • Adamson ED, Dettler MJ, Warshaw JB (1981) Functional EGF receptors are present on mouse embryo tissues. Nature 291:656–659

    Google Scholar 

  • Angeletti RH, Angeletti PU, Levi-Montalcini R (1972) Selective accumulation of 125I labelled nerve growth factor in sympathet- ic ganglia. Brain Res 46:421–425

    Google Scholar 

  • Barnes D, Colowich S (1976) Stimulation of sugar uptake in cultured fibroblasts by epidermal growth factor (EGF) and EGF- binding arginine esterase. J Cell Physiol 89:633–640

    Google Scholar 

  • Brunk U, Schellens J, Westermark B (1976) Influence of epidermal growth factor (EGF) on ruffling activity, pinocytosis and prolif- eration of cultivated human glial cells. Exp Cell Res 103:295–302

    Google Scholar 

  • Byyny RL, Orth DN, Cohen S, Doyne ES (1974) Epidermal growth factor: effects of androgens and adrenergic agents. Endocrinology 95:776–782

    Google Scholar 

  • Carpenter G, Cohen S (1976) Human epidermal growth factor and the proliferation of human fibroblasts. J Cell Physiol 88:227–237

    Google Scholar 

  • Carpenter G, Cohen S (1979) Epidermal growth factor. Ann Rev Biochem 48:193–216

    Google Scholar 

  • Chisolm GM, Silva CA, Hmiel SD (1981) Measurements of the degradation products of radioiodinated proteins. Anal Biochem 111:212–219

    Google Scholar 

  • Cohen S, Fava RA, Sawyer ST (1982) Purification and characterization of epidermal growth factor receptor/protein kinase from normal mouse liver. Proc Natl Acad Sci USA 79:6237–6241

    Google Scholar 

  • Das M (1982) Epidermal growth factor: mechanisms of action. Int Rev Cytol 78:233–256

    Google Scholar 

  • Das M, Miyakawa T, Fox CF, Pruss RM, Aharonov A, Herschman HR (1977) Specific radiolabeling of a cell surface receptor for epidermal growth factor. Proc Natl Acad Sci USA 74:2790–2794

    Google Scholar 

  • Dziegielewska KM, Evans CAN, Fossan G, Corscheider FL, Malinowska DH, Mollgard K, Reynolds ML, Saundes NR, Wilkinson S (1980) Proteins in cerebrospinal fluid and plasma of fetal sheep during development. J Physiol 300:441–455

    Google Scholar 

  • Eng J, Yalow RS (1980) Insulin recoverable from tissues. Diabetes 29:105–109

    Google Scholar 

  • Fallon JH, Serrogy KB, Loughlin SE, Morrison RS, Bradshaw RA, Knauer DJ, Cunningham DD (1984) Epidermal growth factor immunoreactive material in the central nervous system: location and development. Science 224:1107–1109

    Google Scholar 

  • Fischer G (1984) Growth requirements of immature astrocytes in serum-free hormonally defined media. J Neurosci Res 12:543–552

    Google Scholar 

  • Fleming JC, Ting JYP, Stohlman SA, Weiner LP (1983) Improvements in obtaining and characterizing mouse cerebrospinal fluid. J Neuroimmunol 4:129–140

    Google Scholar 

  • Gospodarowizc D, Moran J (1976) Growth factors in mammalian cultures. Ann Rev Biochem 45:531–538

    Google Scholar 

  • Herschman HR, Goodman R, Chandler C, Simpson D, Cawley D, Cole R, Vellis J (1983) Is epidermal growth factor a modulator of nervous system function? In: Haber B, Perez Polo JR, Stella AMG, Paul NW (eds) Nervous system regeneration. Birth defects original article series 19. Alan R Liss, Inc, New York, pp 79–94

    Google Scholar 

  • Hirata Y, Moore GW, Bertagna C, Orth DN (1980) Plasma concentrations of immunoreactive human epidermal growth factor (urogastrone) in man. J Clin Endocrinol Metab 50:440–444

    Google Scholar 

  • Hirata Y, Uchihashi M, Nakajima H, Fujita T, Matsukura S (1982) Presence of epidermal growth factor in human cerebrospinal fluid. J Clin Endocrinol Metab 55:1174–1177

    Google Scholar 

  • Honegger P, Guentert-Lauber B (1983) Epidermal growth factor (EGF) stimulation of cultured brain cells. I. Enhancement of the developmental increase in glial enzymatic activity. Brain Res 11:245–252

    Google Scholar 

  • Hunter WM, Greenwood FC (1962) Preparation of iodine-131 la- belled growth hormone of high specificity. Nature (London) 194:495–496

    Google Scholar 

  • Keefe O'E, Hollenberg MD, Cuatrecasas P (1974) Epidermal growth factor: Characteristics of specific binding in membranes from liver placenta and other target tissues. Arch Biochem Biophys 164:518–526

    Google Scholar 

  • Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685

    PubMed  Google Scholar 

  • Leutz A, Schachner M (1981) Epidermal growth factor (EGF) stimulates DNA-synthesis of astrocytes in primary cerebellar cultures. Cell Tissue Res 220:393–404

    Google Scholar 

  • Leutz A, Schachner M (1982) Cell type specificity of epidermal growth factor (EGF) binding in primary cultures of early post- natal mouse cerebellum. Neurosci Lett 30:179–182

    Google Scholar 

  • Margolis RU, Altszuler N (1967) Insulin in the cerebrospinal fluid. Nature 215:1375–1376

    Google Scholar 

  • Murdoch GH, Potter E, Nicolaisen AK, Evans RM, Rosenfeld MG (1982) Epidermal growth factor rapidly stimulates prolactin gene transcription. Nature 300:192–194

    Google Scholar 

  • Oldendorf WH (1971) Brain uptake of radiolabeled amino acids, amines and hexose after arterial injection. Am J Physiol 221:1629–1639

    Google Scholar 

  • Pardridge WM (1983) Neuropeptides and the blood-brain barrier. Ann Rev Physiol 45:73–82

    Google Scholar 

  • Raff MC, Abney ER, Cohen J, Lindsay R, Noble M (1983) Two types of astrocytes in cultures of developing rat white matter: differences in morphology, surface gangliosides, and growth characteristics. J Neurosci 3:1289–1300

    Google Scholar 

  • Reed DJ, Woodbury DM (1963) Kinetics of movement of iodide, sucrose, inulin and radioidinated serum albumin in the central nervous system and cerebrospinal fluid of the rat. J Physiol 169:816–850

    Google Scholar 

  • Rothman AR, Freireich EJ, Gaskins JR, Patlak CS, Rall DP (1961) Exchange of inulin and dextran between blood and cerebrospi- nal fluid. Am J Physiol 201:1145–1148

    Google Scholar 

  • Rozengurt E, Heppel L (1975) Serum rapidly stimulates ouabain- sensitive 86Rb+ influx in quiescent 3T3 cells. Proc Natl Acad Sci USA 72:4492–4495

    Google Scholar 

  • Savage CR, Cohen S (1972) Epidermal growth factor and a new derivate. J Biol Chem 247:7609–7611

    Google Scholar 

  • Severs WB, Changaris DG, Keil LC, Summy-Long JY, Klase PA, Kapsha JM (1978) Pharmacology of angiotensin-induced drinking behavior. Fed Proc 37:2699–2703

    Google Scholar 

  • Woods SC, Porte D (1977) Relationship between plasma and cerebrospinal fluid insulin levels of dogs. Am J Physiol 233 (4):E331-E334

    Google Scholar 

Download references

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Author notes

  1. Klaus Armin Nave

    Present address: Scripps Clinic and Research Foundation, 92037, La Jolla, CA, USA

Authors and Affiliations

  1. Department of Neurobiology, University of Heidelberg, Heidelberg, Germany

    Klaus Armin Nave, Rainer Probstmeier & Melitta Schachner

Authors
  1. Klaus Armin Nave
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  2. Rainer Probstmeier
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  3. Melitta Schachner
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Nave, K.A., Probstmeier, R. & Schachner, M. Epidermal growth factor does not cross the blood-brain barrier. Cell Tissue Res. 241, 453–457 (1985). https://doi.org/10.1007/BF00217193

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