Cellular and Sub-Cellular Localization of Brain Neurotensin Receptors

  • Alain Beaudet
  • Eva Szigethy
  • Jean Pierre Kessler
  • Corinne Dana
  • Jean Mazella
  • Emmanuel Moyse
Part of the Biochemical Endocrinology book series (BIOEND)


Neurotensin (NT) is a tridecapeptide which was first isolated (Carraway and Leeman, 1973) and sequenced (Carraway and Leeman, 1975) from bovine hypothalamus and later shown by radioimmunoassay (Carraway and Leeman, 1976; Uhl and Snyder, 1976; Kobayashi et al., 1977) and immunohistochemistry (Jennes et al., 1982; Uhl et al., 1977; Uhl et al., 1979) to be distributed throughout the central nervous system (CNS) of various mammalian species, including man. Biochemical and electrophysiological evidence support the view that NT acts as a neurotransmitter/neuromodulator in the mammalian CNS. It is concentrated in synaptosomal fractions (Uhl and Snyder, 1976), is released in a Ca++-dependent manner by depolarizing stimuli (Iversen et al., 1978; Maeda and Frohman, 1981), and is rapidly inactivated by synaptosomal enzymatic systems (Checler et al., 1983, 1984, 1985). It was shown to exert powerful depolarizing effects on neurons in several brain regions (Young et al., 1978; Henry, 1982; Pinnock, 1985) and to activate intracellular second messenger systems both in cell cultures (Amar et al., 1985) and in brain slices (Gilbert et al., 1984; Goedert et al., 1984).


Substantia Nigra Ventral Tegmental Area Basal Forebrain Nucleus Basalis Nodose Ganglion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Amar, S., Mazella, J., Checler, F., Kitabgi, P. and Vincent, J.P., 1985, Regulation of cyclic GMP levels by neurotensin in neuroblastoma clone N1E115. Biochem. Biophys. Res. Commun., 129: 117–125.PubMedCrossRefGoogle Scholar
  2. Andrade, R. and Aghajanian, G.K., 1981, Neurotensin selectively activates dopaminergic neurons of the substantia nigra. Soc. Neurosci. Abst., 7: 573.Google Scholar
  3. Beaudet, A., Hamel, E., Leonard, K., Vial, M., Moyse, E., Kitabgi, P., Vincent, J.P. and Rostène, W., 1988, Autoradiographic localization of brain peptide receptors at the electron microscopic level, in: “Neurotransmitters and Cortical Function: From Molecules to Mind”, M. Avoli, T.A. Reader, R.Y. Dykes and P. Gloor, eds., Plenum Press, New York, pp. 547–563.CrossRefGoogle Scholar
  4. Blackett, N.M. and Parry, D.M., 1977, A simplified method of “hypothetical grain” analysis of electron microscope autoradiographs. J. Histochem. Cytochem., 25: 206–214.Google Scholar
  5. Carraway, R.E. and Leeman, S.E., 1973, The isolation of a new hypotensive peptide, neurotensin, from bovine hypothalami. J. Biol. Chem., 248: 6854–6861.Google Scholar
  6. Carraway, R.E. and Leeman, S.E., 1975, The amino acid sequence of a hypothalamic peptide, neurotensin. J. Biol. Chem., 250: 1907–1911.Google Scholar
  7. Carraway, R.E. and Leeman, S.E., 1976, Characterization of radioimmunoassayable neurotensin in the rat. Its diferential distribution in the central nervous system, small intestine and stomach. J. Biol. Chem., 251: 7045–7052.Google Scholar
  8. Checler, F., Emson, P.C., Vincent, J.P. and Kitabgi, P., 1984, Irjaptivation of neurotensin by rat brain synaptic membranes. Cleavage at the pro10 -tyr11 bond by endo peptidase 24.11 (enkephalinase) and a peptidase different from proline endo peptidase. J. Neurochem., 43: 1295–1301.PubMedCrossRefGoogle Scholar
  9. Checler, F., Vincent, J.P. and Kitabgi, P., 1983, Degradation of neurotensin by rat synaptic membranes: involvement of a thermolysin-like metallo-endopeptidase (enkephalinase), angiotensin-converting enzyme and other unidentified peptidase. J. Neurochem., 41: 375–384.PubMedCrossRefGoogle Scholar
  10. Checler, F., Vincent, J.P. and Kitabgi, P., 1985, Inactivation of neurotensin by rat brain synaptic membranes partly occurs through cleavage at ARG -ARG peptide bond by metalloendopeptidase. J. Neurochem., 45: 1509–1513.PubMedCrossRefGoogle Scholar
  11. Chubb, I.W., 1984, Acetylcholinesterase: multiple functions?, in: “Cholinesterases: Fundamental and Applied Aspects”, M. Brzen, T. Kiauta and E.A. Barnard, eds., Walter de Gruyter, Berlin, pp. 345–359.Google Scholar
  12. Chubb, W., Hodgson, A.J. and White G.H., 1980, Acetylcholinesterase hydrolyzes substance P. Neurosci., 5: 2065–2072.CrossRefGoogle Scholar
  13. Dahlstrom, A. and Fuxe, K., 1964, Evidence for the existence of monoamine-containing neurons in the central nervous system. I. Demonstration of monoamines in the cell bodies of brain stem neurons. Acta Physiol. Scand., 62: 1–55.Google Scholar
  14. Dana, C., Vial, M., Leonard, K., Beauregard, A., Kitabgi, P., Vincent, J.P., Rostène, W. and Beaudet, A. Electron microscopic localization of neurotensin receptors in the midbrain tegmentum of the rat. I. Ventral tegmental area and interfascicular nucleus. Submitted.Google Scholar
  15. Descarries, L. and Beaudet, A., 1983, The use of radioautography for investigating transmitter-specific neurons, in: “Handbook of Chemical Neuroanatomy, Vol. 1: Methods in Chemical Neuroanatomy”, A. Bjorklund and T. Hokfelt, eds., Elsevier, Amsterdam, pp. 286–364.Google Scholar
  16. Eckenstein, F. and Sofroniew, M.V., 1983, Identification of central cholinergic neurons containing both choline acetyl transferase and acetylcholinesterase and of central neurons containing only acetylcholinesterase. J. Neurosci., 3: 2286–2291.PubMedGoogle Scholar
  17. Gilbert, J.A., McKinney, M. and Richelson, F., 1984, Neurotensin stimulates cGMP formation in neuroblastoma clone N1E115 and rat cerebellum. Soc. Neurosci. Abst., 10: 378.Google Scholar
  18. Goedert, M., Pittaway, K. and Emson, P.C., 1984, Neurotensin receptors in the rat striatum: lesion studies. Brain Res., 299: 164–168.PubMedCrossRefGoogle Scholar
  19. Hamel, E. and Beaudet, A., 1984, Localization of opioid binding sites in rat brain by electron microscopic radioautography. J. Electron Microsc. Tech., 1: 317–329.Google Scholar
  20. Hamel, E. and Beaudet, A., 1987, Opioid receptors in rat neostriatum: radioautographic distribution at the electron microscopic level. Brain Res., 401: 239–257.PubMedCrossRefGoogle Scholar
  21. Henry, J.L., 1982, Electrophysiological studies on the neuroactive properties of neurotensin. Ann. N.Y. Acad. Sci., 400: 216–227.Google Scholar
  22. Iversen, L.L., Iversen, S.D., Bloom, F., Douglas, C., Brown, M. and Vale, W., 1978, Calcium-dependent release of somatostatin and neurotensin from rat brain “in vitro”. Nature (Lond.), 273: 161–163.CrossRefGoogle Scholar
  23. Jennes, L., Stumpf, W.E. and Kalivas, P.W., 1982, Neurotensin: topographical distribution in rat brain by immunohistochemistry. J. Comp. Neurol., 210: 211–224.PubMedCrossRefGoogle Scholar
  24. Kalivas, P.W., 1985, Interaction between neuropeptides and dopamine neurons in the ventromedial mesencephalon. Neurosci. & Behav. Rev., 9: 573–587.CrossRefGoogle Scholar
  25. Kessler, J.P. and Beaudet, A. Selective association of neurotensin binding sites with sensory and visceromotor components of the vagus nerve. Submitted.Google Scholar
  26. Kessler, J.P., Moyse, E., Kitabgi, P., Vincent, J.P. and Beaudet, A., 1987, Distribution of neurotensin binding sites in the caudal brainstem of the rat: a light microscopic radioautographic study. Neurosci., 23: 189–198.CrossRefGoogle Scholar
  27. Kitabgi, P., Checler F., Mazella, J. and Vincent, J.P., 1985, Pharmacology and biochemistry of neurotensin receptors. Rev. Clin. Bas. Pharmacol., 5: 397–486.Google Scholar
  28. Kobayashi, R.M., Brown, M. and Vale, W., 1977, Regional distribution of neurotensin and somatostatin in rat brain. Brain Res., 126: 584–588.PubMedCrossRefGoogle Scholar
  29. Laduron, P., 1987, Axonal transport of neuroreceptors: possible involvement in long-term memory. Neurosci., 22: 767–779.CrossRefGoogle Scholar
  30. Lazarus, L.H., Brown, M.R. and Perrin, M.H., 1977, Distribution, localization and characterization of neurotensin binding sites in rat brain. Neuropharmacol., 16: 625–629.CrossRefGoogle Scholar
  31. Levey, A.I., Wainer, B.H., Mufson, E.J. and Mesulam, M.-M., 1983, Co-localization of acetylcholinesterase and choline acetyltransferase in the rat cerebrum. Neurosci., 9: 9–22.CrossRefGoogle Scholar
  32. Maeda, K. and Frohman, L.A., 1981, Neurotensin release by rat hypothalamic fragments in vitro. Brain Res., 210: 261–269.PubMedCrossRefGoogle Scholar
  33. Moyse, E., Rostène, W., Vial, M., Loenard, K., Mazella, J., Kitabgi, P., Vincent, J.P. and Beaudet, A., 1987, Distribution of neurotensin bindkug sites in rat brain: a light microscopic radioauto graphic study using monoiodo (I)Tyr3-neurotensin. Neurosci., 22: 525–536.CrossRefGoogle Scholar
  34. Myers, R.D. and Lee, T.F., 1983, In vivo release of dopamine during perfusion of neurotensin in substantia nigra of unrestrained rat. Peptides, 4: 955–961.PubMedCrossRefGoogle Scholar
  35. Pinnock, R.D., 1985, Neurotensin depolarizes substantia nigra dopaminergic neurons. Brain Res., 338: 151–154.PubMedCrossRefGoogle Scholar
  36. Porter, C., Barnard, E.A. and Chiu, T.H., 1973, The ultrastructural localization and quantitation of cholinergic receptors at the mouse motor endplate. J. Membrane Biol., 14: 383–402.CrossRefGoogle Scholar
  37. Quirion, R., Gaudreau, P., St-Pierce, S., Rioux, F. and Pert, C.B., 1982, Autoradiographic distribution of (3H)neurotensin receptors in rat brain: visualization by tritium sensitive film. Peptides, 3: 757–763.PubMedCrossRefGoogle Scholar
  38. Sadoul, J.L., Mazella, J., Amar, S., Kitabgi, P. and Vincent, J.P., 1984, Preparation of neurotensin selectively iodinated on the tyrosine 3 residue. Biological activity and binding properties on mammalian neurotensin receptors. Biochem. Biophys. Res. Commun., 120: 812–819.PubMedCrossRefGoogle Scholar
  39. Salpeter, M.M., Fertuck, H.C. and Salpeter, E.E., 1977, Resolution in electron microscope autoradiography. III. Iodine-125, the effect of heavy metal staining, and a reassessment of critical parameters. J. Cell Biol., 72: 161–173.PubMedCrossRefGoogle Scholar
  40. Salpeter, M.M., McHenry, F.A. and Salpeter, E.E., 1978, Resolution in electron microscope autoradiography. IV. Application to analysis of autoradio graphs. J. Cell. Biol., 76: 127–145.PubMedCrossRefGoogle Scholar
  41. Sarrieau, A., Javoy-Agid, F., Kitabgi, P., Dussaillant, M., Vial, M., Vincent, J.P., Agid, Y. and Rostène, W.H., 1985, Characterization and autoradiographic distribution of neurotensin binding sites in the human brain. Brain Res., 348: 375–380.PubMedCrossRefGoogle Scholar
  42. Satoh, K., Armstrong, D.M. and Fibiger, H.C., 1983, A comparison of the distribution of central cholinergic neurons as demonstrated by acetylcholinesterase pharmacohistochemistry and choline acetyl transferase immunohistochemistry. Brain Res Bull., 11: 693–720.PubMedCrossRefGoogle Scholar
  43. Schmitt, F.O., 1984, Molecular regulators of brain function: a new view. Neurosci., 13: 991–1001.CrossRefGoogle Scholar
  44. Szigethy, E. and Beaudet, A., 1987, Selective association of neurotensin receptors with cholinergic neurons in the rat basal forebrain. Neurosci. Lett., 83: 47–52.PubMedCrossRefGoogle Scholar
  45. Szigethy, E. and Beaudet, A. Correspondence between high affinity 125I-neurotensin binding sites and dopaminergic neurons in the rat substantia nigra and ventral tegmental area: a combined radioautographic and immunohistochemical light microscopic study. Submitted.Google Scholar
  46. Uhl, G.R., 1982, Distribution of neurotensin and its receptors in the central nervous system. Ann. N.Y. Acad. Sci., 400: 132–149.PubMedCrossRefGoogle Scholar
  47. Uhl, G.R., Goodman, R.R. and Snyder, S.H., 1979, Neurotensin-containing cell bodies, fibers and nerve terminals in the brain stem of the rat: immunohistochemical mapping. Brain Res., 167: 77–91.PubMedCrossRefGoogle Scholar
  48. Uhl, G.R., Kuhar, M.J. and Snyder, S.H., 1977, Neurotensin: immunohistochemical localization in rat central nervous system. Proc. Natl. Acad. Sci. U.S.A., 74: 4059–4063.PubMedCrossRefGoogle Scholar
  49. Uhl, G.R. and Snyder, S.H., 1976, Regional and subcellular distributions of brain neurotensin. Life Sci., 19:1827–1832.PubMedCrossRefGoogle Scholar
  50. Williams, M.A., 1969, The assessment of electron microscopic autoradiography, in: “Advances in Optical and Electron Microscopy”, R. Barer and V.E. Cosslett, eds., Academic Press, London, 3: 219–272.Google Scholar
  51. Young, W.S., III and Kuhar, M.J., 1979, Neurotensin receptors: autoradiographic localization in rat CNS. Eur. J. Pharmacol., 59: 161–163.PubMedCrossRefGoogle Scholar
  52. Young, W.S., III, Uhl, G.R. and Kuhar, M.J., 1978, Iontophoresis of neurotensin in the area of the locus coeruleus. Brain Res., 150: 431–435.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Alain Beaudet
    • 1
  • Eva Szigethy
    • 1
  • Jean Pierre Kessler
    • 1
  • Corinne Dana
    • 2
  • Jean Mazella
    • 3
  • Emmanuel Moyse
    • 1
  1. 1.Montreal Neurological InstituteMontrealCanada
  2. 2.INSERM U.55Centre de Recherches Saint-AntoineParis, Cedex 12France
  3. 3.Centre de Biochimie du CNRSUniversité de NiceNice, CedexFrance

Personalised recommendations