Skip to main content
SpringerLink
Log in
Book cover

Neurotransmitters and Cortical Function pp 547–563Cite as

Autoradiographic Localization of Brain Peptide Receptors at the Electron Microscopic Level

  • Chapter

Abstract

Neurotransmitters and related drugs exert their biochemical, electrophysiological, and, ultimately, behavioral effects by acting upon specific receptor molecules embedded in neuronal and, in some cases, perhaps also glial plasma membranes. This interaction involves: (1) recognition of a specific binding site on the surface of the receptor and (2) translation of the recognition information into a response signal. Pioneering studies by Clark (1933) demonstrated that the binding of drugs (ligands) to receptors was reversible, obeyed the law of mass action, and occurred at very low concentrations of ligand. Considerable progress in our understanding of receptor mechanisms was later to emerge from the development of sensitive methods for measuring the receptor-specific binding of radiolabeled ligand probes (Snyder and Bennett, 1976). Not only did the availability of such methods greatly facilitate the biophysical, pharmacological, and molecular characterization of receptors for neurotransmitters, but it also made possible their localization in situ, using autoradiographic techniques.

This is a preview of subscription content, 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   84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
Price excludes VAT (USA)
  • Compact, lightweight 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

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Altschuler, R. A., Betz, H., Parakkal, M. H., Reeks, K. A., and Wenthold, R. J., 1986, Identification of glycinergic synapses in the cochlear nucleus through immunocytochemical localization of the postsynaptic receptor, Brain Res. 369:316–320.

    Article  PubMed  CAS  Google Scholar 

  • Antkiewicz-Michaluk, L., Havemann, U., Vetulani, J., Wellstein, A, and Kuschinsky, K., 1984, Opioid-specific recognition sites of the mu- and the delta-type in rat striatum after lesions with kainic acid, Life Sci. 35:347–355.

    Article  PubMed  CAS  Google Scholar 

  • Arimatsu, Y., Seto, A., and Amano, T., 1978, Localization of α-bungarotoxin binding sites in mouse brain by light and electron microscopic autoradiography, Brain Res. 147:165–169.

    Article  PubMed  CAS  Google Scholar 

  • Atweh, S. F., and Kuhar, M. J., 1977, Autoradiographic localization of opiate receptors in rat brain. III. The telencephalon, Brain Res. 134:393–405.

    Article  PubMed  CAS  Google Scholar 

  • Beaudet, A., and Descarries, L., 1978, The monoamine innervation of rat cerebral cortex: Synaptic and nonsynaptic axon terminals, Neuroscience 3:851–860.

    Article  PubMed  CAS  Google Scholar 

  • Beaudet, A., Trémeau, O., Ménez, A., and Droz, B., 1979, Visualisation des récepteurs aux opiacés dans le locus coeruleus du rat: Étude radioautographique à haute resolution après administration d’un analogue tritié de la met-enképhaline, CR. Acad. Sci. 289:591–594.

    CAS  Google Scholar 

  • Beaudet, A., Leonard, K., Vial, M., Moyse, E., Kitabgi, P., Vincent, J. P., and Rostène W., 1987, Electron microscopic localization of neurotensin receptors in the substantia nigra of the rat, Soc. Neurosci. Abstr. 13:563.

    Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Bowen, W. D., Pert, C. B., and Pert, A., 1982, Nigral 6-hydroxydopamine lesions equally decrease μ and δ opiate binding to striatal patches: Further evidence for a conformationally malleable type 1 opiate receptor, Life Sci. 31:1679–1682.

    Article  PubMed  CAS  Google Scholar 

  • Chang, K. J., Cooper, B. R., Hazum, E., and Cuatrecasas, P., 1979, Multiple opiate receptors: Different regional distribution in the brain and differential binding of opiates and opioid peptides, Mol. Pharmacol. 16:91–104.

    PubMed  CAS  Google Scholar 

  • Childers, S. R., Schwarcz, R., Coyle, J. T., and Snyder, S. H., 1978, Radioimmunoassay of enkephalins: Levels of methionine- and leucine-enkephalin in morphine dependent and kainic acid lesioned rat brains, in: Advances in Biochemical Psychopharmacology, Vol. 18 (E. Costa and M. Trabucchi, eds.), Raven Press, New York, pp. 161–173.

    Google Scholar 

  • Clark, A. J., 1933, The Mode of Action of Drugs on Cells, Arnold, London.

    Google Scholar 

  • Cuello, A. C., 1983, Nonclassical neuronal communication, Fed. Proc. Fed. Am. Soc. Exp. Biol. 42:2912–2922.

    CAS  Google Scholar 

  • Dana, C, Vial, M., Kitabgi, P., Leonard, K., Beaudet, A., and Rostène, W., 1985, Distribution radioautographique et ultrastructurale des sites de liaison de la neurotensine dans le cerveau de rat, Ann. Endocrinol. 46:16N.

    Google Scholar 

  • Dana, C, Leonard, K., Vial, M., Rostène, W., and Beaudet, A., 1987, Autoradiographic localization of neurotensin binding sites in rat ventral tegmental area at the electron microscopic level, Neuroscience 22:5785.

    Google Scholar 

  • Demoliou-Mason, C. D., and Barnard, E. A., 1986, Distinct subtypes of the opioid receptor with allosteric interactions in brain membranes, J. Neurochem. 46:1118–1128.

    Article  PubMed  CAS  Google Scholar 

  • Descarries, L., and Beaudet, A., 1983, The use of radioautography for investigating transmitter-specific neurons, in: Handbook of Chemical Neuroanatomy, Vol. 1 (A. Björklund and T. Hökfelt, eds.), Elsevier, Amsterdam, pp. 286–364.

    Google Scholar 

  • Descarries, L., Beaudet, A., and Watkins, K. C., 1975, Serotonin nerve terminals in adult rat neocortex, Brain Res. 100:563–588.

    Article  PubMed  CAS  Google Scholar 

  • Gardner, E. L., Zukin, S. R., and Makman, M. H., 1980, Modulation of opiate receptor binding in striatum and amygdala by selective mesencephalic lesions, Brain Res. 194:232–239.

    Article  PubMed  CAS  Google Scholar 

  • Goodman, R. R., Snyder, S. H., Kuhar, M. J., and Young, W. S., III, 1980, Differentiation of delta and mu opiate receptor localizations by light microscopic autoradiography, Proc. Natl. Acad. Sci. USA 77:6239–6243.

    Article  PubMed  CAS  Google Scholar 

  • Hamel, E., and Beaudet, A., 1984a, Localization of opioid binding sites in rat brain by electron microscopic radioautography, J. Electron Microsc. Tech. 1:317–329.

    Article  CAS  Google Scholar 

  • Hamel, E., and Beaudet, A., 1984b, Electron microscopic autoradiographic localization of opioid receptors in rat neostriatum, Nature 312:155–157.

    Article  PubMed  CAS  Google Scholar 

  • Hamel, E., and Beaudet, A., 1987, Opioid receptors in rat neostriatum: Radioautographic distribution at the electron microscopic level, Brain Res. 401:239–257.

    Article  PubMed  CAS  Google Scholar 

  • Hazum, E., Chang, K.-J., and Cuatrecasas, P., 1980, Cluster formation of opiate (enkephalin) receptors in neuroblastoma cells: Differences between agonists and antagonists and possible relationships to biological functions, Proc. Natl. Acad. Sci. USA 77:3038–3041.

    Article  PubMed  CAS  Google Scholar 

  • Herkenham, M., 1984, Autoradiographic demonstration of receptor distributions, in: Brain Receptor Methodologies, Part A (P. J. Marangos, I. C. Campbell, and R. M. Cohen, eds.), Academic Press, New York, pp. 127–152.

    Google Scholar 

  • Herkenham, M., and McLean, S., 1986, Mismatches between receptor and transmitter localizations in the brain, in: Quantitative Receptor Autoradiography, Vol. 19 (C. A. Boast, E. A. Snowhill, and C. A. Altar, eds.), Liss, New York, pp. 137–171.

    Google Scholar 

  • Herkenham, M., and Pert, C.B., 1982, Light microscopic localization of brain opiate receptors: A general auto-radiographic method which preserves tissue quality, J. Neurosci. 2:1129–1149.

    PubMed  CAS  Google Scholar 

  • Hökfelt, T., Everitt, B. J., Theodorsson-Norheim, E., and Goldstein, M., 1984, Occurrence of neurotensinlike immunoreactivity in subpopulations of hypothalamic, mesencephalic, and medullary catecholamine neurons, J. Comp. Neurol. 222:543–559.

    Article  PubMed  Google Scholar 

  • Hollt, V., and Herz, A., 1978, In vivo receptor occupation by opiates and correlation to the pharmacological effect, Fed. Proc. Fed. Am. Soc. Exp. Biol. 37:158–161.

    CAS  Google Scholar 

  • Hunt, S. P., and Schmidt, J., 1978, The electron microscopic autoradiographic localization of α-bungarotoxin binding sites within the central nervous system of the rat, Brain Res. 142:152–159.

    Article  PubMed  CAS  Google Scholar 

  • Jacob, M. H., and Berg, D. K., 1983, The ultrastructural localization of α-bungarotoxin binding sites in relation to synapses on chick ciliary ganglion neurons, J. Neurosci. 3:260–271.

    PubMed  CAS  Google Scholar 

  • Jan, Y. N., and Jan, L. Y., 1983, A LHRH-like peptidergic neurotransmitter capable of ‘action at a distance’ in autonomic ganglia, Trends Neurosci. 6:320–325.

    Article  Google Scholar 

  • Kessler, J. P., Kitabgi, P., and Beaudet, A., 1986, High affinity neurotensin binding to afferent and efferent components of the vagal complex, Soc. Neurosci. Abstr. 12:811.

    Google Scholar 

  • Kitabgi, P., Poustis, C, Granier, C, Van Rietschoten, J., Rivier, J., Morgat, J. L., and Freychet, P., 1980, Neurotensin binding to extraneuronal and neural receptors: Comparison with biological activity and structure activity relationships, Mol. Pharmacol. 18:11–19.

    PubMed  CAS  Google Scholar 

  • Kitabgi, P., Checler, F., Mazella, J., and Vincent, J. P., 1985, Pharmacology and biochemistry of neurotensin receptors, Rev. Clin. Basic Pharmacol. 5:397–486.

    CAS  Google Scholar 

  • Kuhar, M. J., and Yamamura, H. I., 1974, Light microscopic autoradiographic localization of cholinergic muscarinic sites in rat brain, Proc. Soc. Neurosci. 4:29.

    Google Scholar 

  • Kuhar, M. J., Taylor, M., Wamsley, J. K., Hulme, E. C., and Birdsall, N. J. M., 1981, Muscarinic cholinergic receptor localization in brain by electron microscopic autoradiography, Brain Res. 216:1–9.

    Article  PubMed  CAS  Google Scholar 

  • Lentz, T. L., and Chester, J., 1977, Localization of acetylcholine receptors in central synapses, J. Cell Biol. 75:258–267.

    Article  PubMed  CAS  Google Scholar 

  • Lewis, M. E., Khachaturian, H., and Watson, S. J., 1985, Combined autoradiographic-immunocytochemical analysis of opioid receptors and opioid peptide neuronal systems in brain, Peptides 6:37–47.

    Article  PubMed  CAS  Google Scholar 

  • McLean, S., Rothman, R. B., and Herkenham, M., 1986, Autoradiographic localization of μ,- and δ-opiate receptors in the forebrain of the rat, Brain Res. 378:49–60.

    Article  PubMed  CAS  Google Scholar 

  • Miller, M. M., Billiar, R. B., and Beaudet, A., 1987, Ultrastructural distribution of alpha-bungarotoxin binding sites in the suprachiasmatic nucleus of the rat hypothalamus, Cell Tissue Res. (in press).

    Google Scholar 

  • Miller, R. J., Chang, K.-J., Leighton, J., and Cuatrecasas, P., 1978, Interaction of iodinated enkephalin analogs with opiate receptors, Life Sci. 22:379–388.

    Article  PubMed  CAS  Google Scholar 

  • Mohler, H., Richards, J. G., and Wu, J.-Y., 1981, Autoradiographic localization of benzodiazepine receptors in immunocytochemically identified γ-aminobutyrergic synapses, Proc. Natl. Acad. Sci. USA 78:1935–1938.

    Article  PubMed  CAS  Google Scholar 

  • Moyse, E., Vial, M., Leonard, K., Kitabgi, P., Vincent, J. P., Rostène, W., and Beaudet, A., 1985, Electron microscopic visualization of neurotensin binding sites in rat substantia nigra, Soc. Neurosci. Abstr. 11:415.

    Google Scholar 

  • Moyse, E., Pasquini, F., Quirion, R., and Beaudet, A., 1986, 125I-FK 33–824: A selective probe for radio-autographic labeling of μ opioid receptors in the brain, Peptides 7:351–355.

    Article  PubMed  CAS  Google Scholar 

  • Moyse, E., Rostène, W., Vial, M., Leonard, K., Mazella, J., Kitabgi, P., Vincent, J. P., and Beaudet, A., 1987, Regional distribution of neurotensin binding sites in rat brain: A light microscopic radioautographic study usingmonoiodo 125I-Tyr3-neurotensin, Neuroscience 22:525–536.

    Article  PubMed  CAS  Google Scholar 

  • Murrin, L. C., Coyle, J. T., and Kuhar, M. J., 1980, Striatal opiate receptors: Pre- and post-synaptic localization, Life Sci. 27:1175–1183.

    Article  PubMed  CAS  Google Scholar 

  • Palacios, J. M., and Kuhar, M. J., 1981, Neurotensin receptors are located on dopamine-containing neurons in rat midbrain, Nature 294:587–589.

    Article  PubMed  CAS  Google Scholar 

  • Palacios, J. M., Niehoff, D. L., and Kuhar, M. J., 1981, Receptor autoradiography with tritium-sensitive film: Potential for computerized densitometry, Neurosci. Lett. 25:101–105.

    Article  PubMed  CAS  Google Scholar 

  • Parenti, M., Titrone, F., Olgiati, V. R., and Gropetti, A., 1983, Presence of opiate receptors on striatal serotoninergic nerve terminals, Brain Res. 280:317–322.

    Article  PubMed  CAS  Google Scholar 

  • Pert, C. B., Kuhar, M. J., and Snyder, S. H., 1976, Opiate receptors: Autoradiographic localization in rat brain, Proc. Natl. Acad. Sci. USA 73:3729–3733.

    Article  PubMed  CAS  Google Scholar 

  • Pollard, H., Llorens, C, Schwartz, J. C., Gros, C, and Dray, F., 1978, Localization of opiate receptors and enkephalins in the rat striatum in relationship with nigrostriatal dopaminergic system: Lesion studies, Brain Res. 151:392–398.

    Article  PubMed  CAS  Google Scholar 

  • Polz-Tejera, G., Schmidt, J., and Karten, H. J., 1975, Autoradiographic localization of α-bungarotoxin-binding sites in the central nervous system, Nature 258:349–351.

    Article  PubMed  CAS  Google Scholar 

  • Porter, C, Barnard, E. A., and Chiu, T. H., 1973, The ultrastructural localization and quantitation of cholinergic receptors at the mouse motor endplate, J. Membr. Biol. 14:383–402.

    Article  PubMed  CAS  Google Scholar 

  • Quirion, R., 1983, Interactions between neurotensin and dopamine in the brain: An overview, Peptides 4:609–615.

    Article  PubMed  CAS  Google Scholar 

  • Quirion, R., Gaudreau, P., St. Pierre, 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.

    Article  PubMed  CAS  Google Scholar 

  • Reisine, T. D., Nagy, J. I., Beaumont, K., Fibiger, H. C., and Yamamura, H. I., 1979, The localization of receptor binding sites in the substantia nigra and striatum of the rat, Brain Res. 177:241–252.

    Article  PubMed  CAS  Google Scholar 

  • Richards, J. G., Schoch, P., Häring, P., Takacs, B., and Möhler, H., 1987, Resolving GABAA/benzodiazepine receptors: cellular and subcellular localization in the CNS with monoclonal antibodies, J. Neurosci. 7:1866–1886.

    PubMed  CAS  Google Scholar 

  • Roemer, D., Buescher, H. H., Hill, R. C., Pless, J., Bauer, W., Cardinaux, F., Closse, A., Hauser, D., and Huguenin, R., 1977, A synthetic enkephalin analogue with prolonged parenteral and oral analgesic activity, Nature 268:547–549.

    Article  PubMed  CAS  Google Scholar 

  • Rotter, A., Birdsall, N. J. M., Burgen, A. S. V., Field, P. M., and Raisman, G., 1977, Axotomy causes loss of muscarinic receptors and loss of synaptic contacts in the hypoglossal nucleus, Nature 266:734–735.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Salpeter, M. M., McHenry, F. A., and Salpeter, E. E., 1978, Resolution in electron microscope autoradiography. IV. Application to analysis of autoradiographs, J. Cell Biol. 76:127–145.

    Article  PubMed  CAS  Google Scholar 

  • Schmidt, F. O., 1984, Molecular regulators of brain function: A new view, Neuroscience 13:991–1001.

    Article  Google Scholar 

  • Schubert, P., Höllt, V., and Herz, A., 1975, Autoradiographic evaluation of the intracerebral distribution of 3H-etorphine in the mouse brain, Life Sci. 16:1855–1856.

    Article  PubMed  CAS  Google Scholar 

  • Seidah, N. G., Dennis, M., Corvol, R., Rochemont, J., and Chrétien, M., 1980, A rapid high-performance liquid chromatography purification method of iodinated polypeptide hormones, Anal. Biochem. 109:185–191.

    Article  PubMed  CAS  Google Scholar 

  • Snyder, S. H., and Bennett, J. P., Jr., 1976, Neurotransmitter receptors in the brain: Biochemical identification, Annu. Rev. Physiol. 38:153–175.

    Article  PubMed  CAS  Google Scholar 

  • Strader, C. D., Pickel, V. M., Joh, T. H., Strohsacker, M. W., Shorr, R. G. L., Lefkowitz, R. J., and Caron, M. G., 1983, Antibodies to the α-adrenergic receptor: Attenuation of catecholamine-sensitive adenylate cyclase and demonstration of postsynaptic receptor localization in brain, Proc. Natl. Acad. Sci. USA 80:1840–1844.

    Article  PubMed  CAS  Google Scholar 

  • Szigethy, E., Kitabgi, P., and Beaudet, A., 1986, Localization of neurotensin binding sites to dopaminergic and putative cholinergic neurons in rat central nervous system, Soc. Neurosci. Abstr. 12:1003.

    Google Scholar 

  • Trémeau, O., Faure, G., Boulain, J. C., Bouet, F., Ménez, A., Lecocq, G., Morgat, J. L., and Fromageot, P.,1981, Liaison d’un analogue enképhalinergique (FK 33–824) tritié à une fraction mitochondriale de cerveau de rat, Biochimie 63:477–484.

    Article  PubMed  Google Scholar 

  • Triller, A., Cluzeaud, F., Pfeiffer, F., Betz, H., and Korn, H., 1985, Distribution of glycine receptors at central synapses: An immunoelectron microscopy study, J. Cell Biol. 101:683–688.

    Article  PubMed  CAS  Google Scholar 

  • Uhl, G. R., 1982, Distribution of neurotensin and its receptors in the central nervous system, Ann. N.Y. Acad. Sci. 400:132–149.

    Article  PubMed  CAS  Google Scholar 

  • Van Loon, G. R., and George, S. R., 1983, Uptake/internalization of met-enkephalin by brain synaptosomes, Life Sci. 33:145–148.

    Article  PubMed  Google Scholar 

  • Williams, M. A., 1969, The assessment of electron microscopic autoradiography, in: Advances in Optical and Electron Microscopy, Vol. 3 (R. Barer and V. E. Cosslett, eds.), Academic Press, New York, pp. 219–272.

    Google Scholar 

  • Young, W. S., III, and Kuhar, M. J., 1979a, A new method for receptor autoradiography: [3H]opioid receptors in rat brain, Brain Res. 179:255–270.

    Article  PubMed  CAS  Google Scholar 

  • Young, W. S., III, and Kuhar, M. J., 1979b, Neurotensin receptors: Autoradiographic localization in rat CNS, Eur. J. Pharmacol. 59:161–163.

    Article  PubMed  Google Scholar 

  • Young, W. S., III, and Kuhar, M. J., 1981, Neurotensin receptor localization by light microscopic autoradiography in rat brain, Brain Res. 206:272–285.

    Article  Google Scholar 

  • Young, W. S., Wamsley, J. K., Zarbin, M. A., and Kuhar, M. J., 1980, Opioid receptors undergo axonal transport, Science 210:76–77.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Montreal Neurological Institute, McGill University, Montreal, Quebec, H3A 2B4, Canada

    A. Beaudet, E. Hamel, K. Leonard & E. Moyse

  2. INSERM U-55, Hôpital St. Antoine, 75012, Paris, France

    M. Vial & W. Rostène

  3. Centre de Biochimie du CNRS, Université de Nice, 06034, Nice Cedex, France

    P. Kitabgi & J. P. Vincent

Authors
  1. A. Beaudet
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. Hamel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K. Leonard
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Vial
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. E. Moyse
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. P. Kitabgi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J. P. Vincent
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. W. Rostène
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. McGill University and Montreal Neurological Institute, Montreal, Quebec, Canada

    Massimo Avoli  & Pierre Gloor  & 

  2. University of Montreal, Montreal, Quebec, Canada

    Tomás A. Reader

  3. McGill University and Royal Victoria Hospital, Montreal, Quebec, Canada

    Robert W. Dykes

Rights and permissions

Reprints and permissions

Copyright information

© 1988 Plenum Press, New York

About this chapter

Cite this chapter

Beaudet, A. et al. (1988). Autoradiographic Localization of Brain Peptide Receptors at the Electron Microscopic Level. In: Avoli, M., Reader, T.A., Dykes, R.W., Gloor, P. (eds) Neurotransmitters and Cortical Function. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-0925-3_35

Download citation

  • DOI: https://doi.org/10.1007/978-1-4613-0925-3_35

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4612-8248-8

  • Online ISBN: 978-1-4613-0925-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation