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Molecular Neuroanatomy of Neurotransmitter Receptors: The Use of in situ Hybridization Histochemistry for the Study of Their Anatomical and Cellular Localization

  • M. T. Vilaró
  • M. I. Martinez-Mir
  • M. Sarasa
  • M. Pompeiano
  • J. M. Palacios
  • G. Mengod
Chapter

Abstract

The concept of neurotransmitter receptor is now nearly a hundred years old. It was proposed initially by Ehrlich and Langley, to explain the mechanism of action of some drugs. The extreme selectivity of some cellular components to recognize members of a given chemical family led these investigators to propose that a ‘receptive substance’ or ‘receptor’ existed (Parascandola, 1980). It was not until the 1930s, with the work of A. J. Clark, that the first quantitative expression of drug-receptor interactions was provided (Brimblecombe 1974). Since then, the receptor concept has developed and those ‘receptive substances’ are today known to be actual molecules. Initially, receptors were defined operationally in preparations of isolated organs by the differential response of those organs to series of drugs belonging to different chemical classes. It was through using this kind of preparation that the difference between muscarinic and nicotinic and between alpha and beta adrenergic receptors was found and the existence of these subtypes was proposed. With the introduction of radiolabeled molecules at the beginning of the 1970s, it was possible directly to label the receptor molecules in cell-free preparations, particularly in membranes. Little by little, the receptors were assuming a molecular aspect and, to quote E. J. Ariëns (1979), evolved ‘from fiction to fact’. Thanks to the development of more and more selective compounds, it was possible to isolate the first receptor proteins. All this work has culminated in the last few years in the isolation and molecular cloning of the genes or cDNAs coding for many of these neurotransmitter receptors. The goal of the present review is to examine the impact that this progress in our understanding of the molecular nature of the receptors has had on our knowledge of neurotransmitter receptor localization.

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References

  1. Akagi, H. and Miledi, R. (1988). Heterogeneity of glycine receptors and their messenger RNAs in rat brain and spinal cord. Science, N. Y., 242, 270–273CrossRefGoogle Scholar
  2. Albert, P., Zhou, Q. Y., Van Tol, H. H. M., Bunzow, J. R. and Civelli, O. (1990). Cloning, functional expression and mRNA tissue distribution of the rat 5-hydroxytryptamine1A receptor gene. J. Biol. Chem., 265, 5825–5832PubMedGoogle Scholar
  3. Angerer, L. M., Stoler, M. H. and Angerer, R. C. (1987). In situ hybridization with RNA probes: an annotated recipe. In In situ Hybridization. Applications to Neurobiology (ed. K. L. Valentino, J. H. Eberwine and J. D. Barchas). Oxford University Press, OxfordGoogle Scholar
  4. Ariëns, E. J. (1979). Receptors: from fiction to fact. Trends Pharmacol. Sci., 1, 11–15CrossRefGoogle Scholar
  5. Barnard, E. A., Darlison, M. G. and Seeburg, P. (1987). Molecular biology of the GABAA receptor: the receptor/channel superfamily. Trends Neurosci., 10, 502–509CrossRefGoogle Scholar
  6. Betz, H. (1987). Biology and structure of the mammalian glycine receptor. Trends Neurosci., 10, 113–117CrossRefGoogle Scholar
  7. Bonner, T. I. (1989). The molecular basis of muscarinic receptor diversity. Trends Neurosci., 12, 148–151PubMedCrossRefGoogle Scholar
  8. Bonner, T. I., Buckley, N. J., Young, A. C. and Brann, M. R. (1987). Identification of a family of muscarinic acetylcholine receptor genes. Science, N. Y., 237, 527–532CrossRefGoogle Scholar
  9. Bonner, T. I., Young, A. C., Brann, M. R. and Buckley, N. J. (1988). Cloning and expression of the human and rat m5 muscarinic acetylcholine receptor genes. Neuron, 1, 403–410PubMedCrossRefGoogle Scholar
  10. Boulter, J., Evans, K., Goldman, D., Martin, G., Treco, D., Heinemann, S. and Patrick, J. (1986). Isolation of a cDNA clone coding for a possible neural nicotinic acetylcholine receptor α-subunit. Nature, 319, 368–374PubMedCrossRefGoogle Scholar
  11. Brimblecombe, R. W. (1974). Historical introduction. In Drug Actions on Cholinergic Systems (Pharmacological Monographs) (ed. P. B. Bradley). Macmillan Press, London, pp. 1–18Google Scholar
  12. Buckley, N. J., Bonner, T. I. and Brann, M. R. (1988). Localization of a family of muscarinic receptor mRNAs in rat brain. J. Neurosci., 8, 4646–4652PubMedGoogle Scholar
  13. Buckley, N. J., Bonner, T. I., Buckley, C. M. and Brann, M. R. (1989). Antagonist binding properties of five cloned muscarinic receptors expressed in CHO-K1 cells. Molec. Pharmacol., 35, 469–476Google Scholar
  14. Bunzow, J. R., Van Toi, H. H. M., Grandy, D. K., Albert, P., Salon, J., Christie, M., Machida, C. A., Neve, K. A. and Civelli, O. (1988). Cloning and expression of a rat D2 dopamine receptor cDNA. Nature, 336, 783–787PubMedCrossRefGoogle Scholar
  15. Chio, C. L., Hess, G. F., Graham, R. S. and Huff, R. M. (1990). A second molecular form of D2 dopamine receptor in rat and bovine caudate nucleus. Nature, 343, 266–269PubMedCrossRefGoogle Scholar
  16. Clarke, P. B. S., Schwartz, R. D., Paul, S. M., Pert, C. B. and Pert, A. (1985). Nicotinic binding in rat brain: autoradiographic comparison of [3H]acetylcholine, [3H]nicotine, and [125I]-α-bungarotoxin. J. Neurosci., 5, 1307–1315PubMedGoogle Scholar
  17. Coghlan, J. P., Aldred, P., Haralambidis, J., Niall, H. D., Penschow, J. D. and Tregear, G. W. (1985). Hybridization histochemistry. Anal. Biochem., 149, 1–28PubMedCrossRefGoogle Scholar
  18. Cortés, R. and Palacios, J. M. (1986). Muscarinic cholinergic receptor subtypes in the rat brain. I. Quantitative autoradiographic studies. Brain Res., 362, 227–238PubMedCrossRefGoogle Scholar
  19. Dal Toso, R., Sommer, B., Ewert, M., Herb, A., Pritchett, D. B., Bach, A., Shivers, B. D. and Seeburg, P. H. (1989). The dopamine D2 receptor: two molecular forms generated by alternative splicing. EMBO Jl, 8, 4025–4034Google Scholar
  20. de Jonge, A., Doods, H. N., Riesbos, J. and van Zwieten, P. A. (1986). Heterogeneity of muscarinic binding sites in rat brain, submandibular gland and atrium. Br. J. Pharmacol., 89, Suppl.,551PGoogle Scholar
  21. Deneris, E. S., Boulter, J., Swanson, L. W., Patrick, J. and Heinemann, S. (1989). β3: a new member of nicotinic acetylcholine receptor gene family is expressed in brain. J. Biol. Chem., 264, 6268–6272PubMedGoogle Scholar
  22. Deneris, E. S., Connolly, J., Boulter, J., Wada, E., Wada, K., Swanson, L. W., Patrick, J. and Heinemann, S. (1988). Primary structure and expression of β2: a novel subunit of neuronal nicotinic acetylcholine receptors. Neuron, 1, 45-54Google Scholar
  23. Deutch, A. Y., Holliday, J., Roth, R. H., Chun, L. L. Y. and Hawrot, E. (1987). Immunohistochemical localization of a neuronal nicotinic acetylcholine receptor in mammalian brain. Proc. Natl Acad. Sci. USA, 84, 8697–8701PubMedPubMedCentralCrossRefGoogle Scholar
  24. Dohlman, H. G., Caron, M. G. and Lefkowitz, R. J. (1987). A family of receptors coupled to guanine nucleotide regulatory proteins. Biochemistry, 26, 2657–2664PubMedCrossRefGoogle Scholar
  25. Duvoisin, R. M., Deneris, E. S., Patrick, J. and Heinemann, S. (1989). The functional diversity of the neuronal nicotinic acetylcholine receptors is increased by a novel subunit: β4. Neuron, 3, 487–496PubMedCrossRefGoogle Scholar
  26. Fargin, A., Raymond, J. R., Lohse, M. J., Kobilka, B. K., Caron, M. G. and Lefkowitz, R. J. (1988). The genomic clone G-21 which resembles a β-adrenergic receptor sequence encodes the 5-HT1A receptor. Nature, 335, 358–360PubMedCrossRefGoogle Scholar
  27. Garrett, K. M., Duman, R. S., Saito, N., Blume, A. J., Vitek, M. P. and Tallman, J. F. (1988).Google Scholar
  28. Isolation of a cDNA clone for the alpha subunit of the human GABA-A receptor. Biochem. Biophys. Res. Commun., 156, 1039–1045Google Scholar
  29. Giros, B., Sokoloff, P., Martres, M.-P., Riou, J.-F., Emorine, L. J. and Schwartz, J. C. (1989). Alternative splicing directs the expression of two D2 dopamine receptor isoforms. Nature, 342, 923–926PubMedCrossRefGoogle Scholar
  30. Gocayne, J., Robinson, D. A., Fitzgerald, M. G., Ghung, F.-Z., Kerlavage, A. R., Lentes, K.-U., Lai, J., Wang, Ch.-D., Fraser, C. M. and Venter, J. C. (1987). Primary structure of rat cardiac β-adrenergic and muscarinic cholinergic receptors obtained by automated DNA sequence analysis: Further evidence for a multigene family. Proc. Natl Acad. Sci. USA, 84, 8296–8300PubMedPubMedCentralCrossRefGoogle Scholar
  31. Goldman, D., Deneris, E., Luyten, W., Kochhar, A., Patrick, J. and Heinemann, S. (1987). Members of a nicotinic acetylcholine receptor gene family are expressed in different regions of the mammalian central nervous system. Cell, 48, 965–973PubMedCrossRefGoogle Scholar
  32. Goldman, D., Simmons, D., Swanson, L. W., Patrick, J. and Heinemann, S. (1986). Mapping of brain areas expressing RNA homologous to two different acetylcholine receptor α-subunit cDNAs. Proc. Natl Acad. Sci. USA, 83, 4076–4080PubMedPubMedCentralCrossRefGoogle Scholar
  33. Grandy, D. K., Marchionni, M. A., Makam, H., Stofko, R. E., Alfano, M., Frothingham, L., Fischer, J.B., Burke-Howie, K.J., Bunzow, J.R., Server, A.C. and Civelli, O. (1989). Cloning of the cDNA and gene for a human D2 dopamine receptor. Proc. Natl Acad. Sci. USA, 86, 9762–9766PubMedPubMedCentralCrossRefGoogle Scholar
  34. Gregor, P., Mano, I., Maoz, I., McKeown, M. and Teichberg, V. I. (1989). Molecular structure of the chick kainate-binding subunit of a putative glutamate receptor. Nature, 342, 689–692PubMedCrossRefGoogle Scholar
  35. Grenningloh, G., Rienitz, A., Schmitt, B., Methfessel, C., Zensen, M., Beyreuther, K., Gundelfinger, E. D. and Betz, H. (1987). The strychnine-binding subunit of the glycine receptor shows homology with nicotinic acetylcholine receptors. Nature, 328, 215–220PubMedCrossRefGoogle Scholar
  36. Hall, Z. W. (1987). Three of a kind: The β-adrenergic receptor, the muscarinic acetylcholine receptor, and rhodopsin. Trends Neurosci., 10, 99–101CrossRefGoogle Scholar
  37. Hamel, E. and Beaudet, A. (1984). Electron microscopic autoradiographic localization of opioid receptors in rat neostriatum. Nature, 312, 155–157PubMedCrossRefGoogle Scholar
  38. Hammer, R., Berrie, C. P., Birdsall, N. J. M., Burgen, A. S. V. and Hulme, E. C. (1980). Pirenzepine distinguishes between different subclasses of muscarinic receptors. Nature, 283, 90–92PubMedCrossRefGoogle Scholar
  39. Hammer, R., Giraldo, E., Schiavi, G. B., Monferini, E. and Ladinsky, H. (1986). Binding profile of a novel cardioselective muscarine receptor antagonist, AF-DX 116, to membranes of peripheral tissues and brain in the rat. Life Sci., 38, 1653–1662PubMedCrossRefGoogle Scholar
  40. Henderson, R. and Unwin, P. N. T. (1975). Three-dimensional model of purple membrane obtained by electron microscopy. Nature, 257, 28–32PubMedCrossRefGoogle Scholar
  41. Hirouchi, M., Kuwano, R., Katagiri, T., Takahashi, Y. and Kuriyama, K. (1989). Nucleotide and deduced amino acid sequences of the GABAA receptor α-subunit from human brain. Neurochem. Int., 15, 33–38PubMedCrossRefGoogle Scholar
  42. Hoch, W., Betz, H. and Becker, C.-M. (1989). Primary cultures of mouse spinal cord express the neonatal isoform of the inhibitory glycine receptor. Neuron, 3, 339–348PubMedCrossRefGoogle Scholar
  43. Hoffman, B. J. and Mezey, E. (1989). Distribution of serotonin 5-HT1C receptor mRNA in adult rat brain. FEBS Lett., 247, 453–462PubMedCrossRefGoogle Scholar
  44. Hollmann, M., O’Shea-Greenfield, A., Rogers, S. W. and Heinemann, S. (1989). Cloning by functional expression of a member of the glutamate receptor family. Nature, 342, 643–648PubMedCrossRefGoogle Scholar
  45. Hucho, F. (1986). The nicotinic acetylcholine receptor and its ion channel. Eur. J. Biochem., 158, 211–226PubMedCrossRefGoogle Scholar
  46. Julius, D., MacDermott, A. B., Axel, R. and Jessel, T. (1988). Molecular characterization of a functional cDNA encoding the serotonin 1c receptor. Science, NY., 241, 558–564CrossRefGoogle Scholar
  47. Kebabian, J. W. and Calne, D. B. (1979). Multiple receptors for dopamine. Nature, 277, 93–96PubMedCrossRefGoogle Scholar
  48. Khrestchatisky, M., MacLennan, A. J., Chiang, M.-Y., Xu, W., Jackson, M. B., Brecha, N., Sternini, C., Olsen, R. W. and Tobin, A. J. (1989). A novel α subunit in rat brain GABAA receptors. Neuron, 3, 745–753PubMedCrossRefGoogle Scholar
  49. Kobilka, B. K., Frielle, T., Collins, S., Yang-Feng, T., Kobilka, T. S., Francke, U., Lefkowitz, R. J. and Caron, M. G. (1987). An intronless gene encoding a potential member of the family of receptors coupled to guanine nucleotide regulatory proteins, Nature, 329, 75–79PubMedCrossRefGoogle Scholar
  50. Kubo, T., Fukuda, K., Mikami, A., Maeda, A., Takahashi, H., Mishina, M., Haga, T., Haga, K., Ichiyama,A., Kangawa, K., Kojima, M., Matsuo, H., Hirose,T. and Numa, S. (1986a). Cloning, sequencing and expression of complementary DNA encoding the muscarinic acetylcholine receptor. Nature, 323, 411–416PubMedCrossRefGoogle Scholar
  51. Kubo, T., Maeda, A., Sugimoto, K., Akiba, I., Mikami, A., Takahashi, H., Haga, T., Haga, K., Ichiyama, A., Kangawa, K., Matsuo, H., Hirose, T. and Numa, S. (1986b). Primary structure of porcine cardiac muscarinic acetylcholine receptor deduced from the cDNA sequence. FEBS Lett., 209, 367–372PubMedCrossRefGoogle Scholar
  52. Kuhar, M. J., De Souza, E. B. and Unnerstall, J. R. (1986). Neurotransmitter receptor mapping by autoradiography and other methods. Ann. Rev. Neurosci., 9, 27–59PubMedCrossRefGoogle Scholar
  53. Le Moine, C., Normand, E., Guitteny, A. F., Fouque, B., Teoule, R. and Bloch, B. (1990). Dopamine receptor gene expression by enkephalin neurons in rat forebrain. Proc. Natl Acad Sci. USA, 87, 230–234PubMedPubMedCentralCrossRefGoogle Scholar
  54. Levitan, E. S., Schofield, P. R., Burt, D. R., Rhee, L. M., Wisden, W., Kohler, M., Fujita, N., Rodriguez, H. F., Stephenson, A., Darlison, M. G., Barnard, E. A. and Seeburg, P. H. (1988). Structural and functional basis for GABAA receptor heterogeneity. Nature, 335, 76–79PubMedCrossRefGoogle Scholar
  55. Lewis, M. E., Krause II, R. G. and Roberts-Lewis, J. M. (1988). Recent developments in the use of synthetic oligonucleotides for in situ hybridization histochemistry. Synapse, 2, 308–316PubMedCrossRefGoogle Scholar
  56. Lolait, S. J., O’Carroll, A.-M., Kusano, K., Muller, J.-M., Brownstein, M. J. and Mahan, L. C. (1989). Cloning and expression of a novel rat GABAA receptor. FEBS Lett., 246, 145–148PubMedCrossRefGoogle Scholar
  57. Lübbert, H., Foguet, M., Hartikka, J., Merguin, L. and Staufenbiel, M. (1990). Molecular biology of the serotoninergic system in the rodent brain. J. Cell. Biochem., Suppl., 14F, CP 205Google Scholar
  58. McCarthy, M. P., Earnest, J. P., Young, E. F., Choe, S. and Stroud, R. M. (1986). The molecular neurobiology of the acetylcholine receptor. Ann. Rev. Neurosci., 9, 383–413PubMedCrossRefGoogle Scholar
  59. Maelicke, A. (1988). Structure and function of the nicotinic acetylcholine receptor. In Handbook of Experimental Pharmacology, Vol. 86, The Cholinergic Synapse (ed. V. P. Whittaker). Springer-Verlag, Berlin, HeidelbergGoogle Scholar
  60. Mamalaki, C., Stephenson, F. A. and Barnard, E. A. (1987). The GABAA/benzodiazepine receptor is a heterotetramer of homologous α and β subunits. EMBO Jl., 6, 561–565Google Scholar
  61. Meador-Woodruff, J. H., Mansour, A., Bunzow, J. R., Van Toi, H. H. M., Watson, S. J. Jr. and Civelli, O. (1989). Distribution of D2 dopamine receptor mRNA in rat brain. Proc. Natl Acad. Sci. USA, 86, 7625–7628PubMedPubMedCentralCrossRefGoogle Scholar
  62. Mengod, G., Martinez-Mir, M. I., Vilarö, M. T. and Palacios, J. M. (1989). Localization of the mRNA for the dopamine D2 receptor in the rat brain by in situ hybridization histochemistry. Proc. Natl Acad. Sci. USA, 86, 8560–8564PubMedPubMedCentralCrossRefGoogle Scholar
  63. Mengod, G., Nguyen, H., Le, H., Waeber, C., Lübbert, H. and Palacios, J. M. (1990a). The distribution and cellular localization of 5-HTlC receptor mRNA in the rodent brain examined by in situ hybridization histochemistry. Comparison with receptor binding distribution. Neuroscience, 35, 577–591PubMedCrossRefGoogle Scholar
  64. Mengod, G., Pompeiano, M., Martinez-Mir, M. L and Palacios, J. M. (1990b). Localization of the mRNA for the 5-HT2 receptor by in situ hybridization histochemistry. Correlation with the distribution of receptor sites. Brain Res. (in press)Google Scholar
  65. Michel, A. D., Delmendo, R., Stefanich, E. and Whiting, R. L. (1989a). Binding characteristics of the muscarinic receptor subtype of the NG108-15 cell line. Arch. Pharmacol., 340, 62–67Google Scholar
  66. Michel, A. D., Stefanich, E. and Whiting, R. L. (1989b). PC12 phaeochromocytoma cells contain an atypical muscarinic receptor binding site. Br. J. Pharmacol., 97, 914–920PubMedPubMedCentralCrossRefGoogle Scholar
  67. Mishina, M., Takai, T., Imoto, K., Noda, M., Takahashi, T., Numa, S., Methfessel, C. and Sakmann, B. (1986). Molecular distinction between fetal and adult forms of muscle acetylcholine receptor. Nature, 321, 406–411PubMedCrossRefGoogle Scholar
  68. Molineaux, S. M., Jessell, T. M., Axel, R. and Julius, D. (1989). 5-HT1C receptor is a prominent serotonin receptor subtype in the central nervous system. Proc. Natl Acad. Sci. USA, 86, 6793–6797PubMedPubMedCentralCrossRefGoogle Scholar
  69. Monsma, F. J. Jr, McVittie, L. D., Gerfen, C. R., Mahan, L. C. and Sibley, D. R. (1989). Multiple D2 dopamine receptors produced by alternative splicing. Nature, 342, 926–929PubMedCrossRefGoogle Scholar
  70. Mulle, C. and Changeux, J.-P. (1990). A novel type of nicotinic receptor in the rat central nervous system characterized by patch-clamp techniques. J. Neurosci., 10, 169–175PubMedGoogle Scholar
  71. Najlerahim, A., Barton, A. J. L., Harrison, P. J., Heffernan, J. and Pearson, R. C. A. (1989). Messenger RNA encoding the D2 dopamine receptor detected by in situ hybridization histochemistry in rat brain. FEBS Lett., 255, 335–339PubMedCrossRefGoogle Scholar
  72. Nef, P., Oneyser, C., Alliod, C., Couturier, S. and Ballivet, M. (1988). Genes expressed in the brain define three distinct neuronal nicotinic acetylcholine receptors. EMBO Jl, 7, 595–601Google Scholar
  73. Novotny, E. A. and Brann, M. R. (1989). Agonist pharmacology of cloned muscarinic receptors. Abstracts from the Fourth International Symposium on Subtypes of Muscarinic Receptors, Wiesbaden, No. 69, Trends Pharmacol. Sci. supplementGoogle Scholar
  74. O’Dowd, B. F., Lefkowitz, R. J. and Caron, M. G. (1989). Structure of the adrenergic and related receptors. Ann. Rev. Neurosci., 12, 67–83PubMedCrossRefGoogle Scholar
  75. Olsen, R. W. (1990). Molecular biology of GABAA receptors. FASEB J., 4, 1469–1480PubMedGoogle Scholar
  76. Olsen, R. W., McCabe, R. T. and Wamsley, J. K. (1990). GABAA receptor subtypes: autoradiographic comparison of GABA, benzodiazepine, and convulsant binding sites in rat central nervous system. J. Chem. Neuroanat., 3, 59–76PubMedGoogle Scholar
  77. Ovchinnikov, Y. A. (1982). Rhodopsin and bacteriorhodopsin: structure-function relationships. FEBS Lett., 148, 179–189PubMedCrossRefGoogle Scholar
  78. Palacios, J. M. and Dietl, M. M. (1988). Autoradiographic studies of serotonin receptors. In The Serotonin Receptors (ed. E. Sanders-Bush). Humana Press, Clifton, New Jersey, pp. 89–138CrossRefGoogle Scholar
  79. Palacios, J. M., Mengod, G., Vilaro, M. T., Wiederhold, K. H., Boddeke, H.W. G. M., Alvarez, F. J., Chinaglia, G. and Probst, A. (1990). Cholinergic receptors in the rat and human brain. Microscopic visualization. Progr. Brain. Res., 84, 343–353Google Scholar
  80. Palacios, J. M., Probst, A. and Cortés, R. (1986). Mapping receptors in the human brain. Trends Neurosci., 9, 284–289CrossRefGoogle Scholar
  81. Palacios, J. M., Wamsley, J. K. and Kuhar, M. J. (1981). High affinity GABA receptors— autoradiographic localization. Brain Res., 222, 285–307PubMedCrossRefGoogle Scholar
  82. Palacios, J. M., Young, W. S. III and Kuhar, M. J. (1980). Autoradiographic localization of γ-aminobutyric acid (GABA) receptors in the rat cerebellum. Proc. Natl Acad. Sci. USA, 77, 670–674PubMedPubMedCentralCrossRefGoogle Scholar
  83. Parascandola, J. (1980). Origins of the receptor theory. Trends Pharmacol. Sci., 1, 189–192CrossRefGoogle Scholar
  84. Peralta, E. G., Ashkenazi, A., Winslow, J. W., Smith, D. H., Ramachandran, J. and Capon, D. J. (1987a). Distinct primary structures, ligand-binding properties and tissue-specific expression of four human muscarinic acetylcholine receptors. EMBO Jl, 6, 3923–3929Google Scholar
  85. Peralta, E. G., Winslow, J. W., Peterson, G. L., Smith, D. H., Ashkenazi, A., Ramachandran, J., Schimerlik, M. I. and Capon, D. J. (1987b) Primary structure and biochemical properties of an M2 muscarinic receptor. Science, N. Y., 236, 600–605CrossRefGoogle Scholar
  86. Persohn, E., Malherbe, P., Pritchett, D. B., Bach, A. W. J., Wozny, M., Taleb, O., Dal Toso, R., Shin, J. C. and Seeburg, P. H. (1988). Structure and functional expression of cloned rat serotonin 5-HT-2 receptor. EMBO Jl, 7, 4135–4140Google Scholar
  87. Pritchett, D. B., Lüddens, H. and Seeburg, P. H. (1989a). Type I and Type II GABAA-benzodiazepine receptors produced in transfected cells. Science, N. Y., 245, 1389–1392CrossRefGoogle Scholar
  88. Pritchett, D. B., Sontheimer, H., Shivers, B. D., Ymer, S., Kettenmann, H., Schofield, P. R. and Seeburg, P. H. (1989b). Importance of a novel GABAA receptor subunit for benzodiazepine pharmacology. Nature, 338, 582–585PubMedCrossRefGoogle Scholar
  89. Quirion, R., Araujo, D., Regenold, W. and Boksa, P. (1989). Characterization and quantitative autoradiographic distribution of [3H]acetylcholine muscarinic receptors in mammalian brain. Apparent labelling of an M2-like receptor subtype. Neuroscience, 29, 271–289PubMedCrossRefGoogle Scholar
  90. Regenold, W., Araujo, D. M. and Quirion, R. (1989). Quantitative autoradiographic distribution of [3H]AF-DX 116 muscarinic-M2 receptor binding sites in rat brain. Synapse, 4, 115–125PubMedCrossRefGoogle Scholar
  91. Richards, J. G. (1990). In situ hybridization histochemistry reveals a diversity of GABAA receptor subunit mRNAs in neurons of the rat spinal cord and dorsal root ganglia. J. Neurosci. (in press)Google Scholar
  92. Richards, J. G., Schoch, P., Häring, P., Takacs, B. and Mönier, H. (1987). Resolving GABAA/benzodiazepine receptors: Cellular and subcellular localization in the CNS with monoclonal antibodies J. Neurosci., 1, 1866–1886Google Scholar
  93. Schofield, P. R., Darlison, M. G., Fujita, N., Burt, D. R., Stephenson, F. A., Rodriguez, H., Rhee, L. M., Ramachandran, J., Reale, V., Glencorse, T. A., Seeburg, P. H. and Barnard, E. A., (1987). Sequence and functional expression of the GABAA receptor shows a ligandgated receptor super-family. Nature, 328, 221–227PubMedCrossRefGoogle Scholar
  94. Schofield, P. R., Pritchett, D. B., Sontheimer, H., Kettenmann, H. and Seeburg, P. H. (1989). Sequence and expression of human GABAA receptor α1 and β1 subunits. FEBS Lett., 244, 361–364PubMedCrossRefGoogle Scholar
  95. Schofield, P. R., Shivers, B. D. and Seeburg, P. H. (1990). The role of receptor diversity in the CNS. Trends Neurosci., 13, 8–11PubMedCrossRefGoogle Scholar
  96. Selbie, L. A., Hayes, G. and Shine, J. (1989). The major dopamine D2 receptor: molecular analysis of the human D2A subtype. DNA, 8, 683–689PubMedCrossRefGoogle Scholar
  97. Séquier, J. M., Richards, J. G., Malherbe, P., Price, G. W., Mathews, S. and Mönier, H. (1988). Mapping of brain areas containing RNA homologous to cDNAs encoding the α and β subunits of the rat GABAA γ-aminobutyrate receptor. Proc. Natl Acad. Sci. USA, 85, 7815–7819PubMedPubMedCentralCrossRefGoogle Scholar
  98. Sheldon, P. W. and Aghajanian, G. K. (1990). Serotonin (5-HT) induces IPSPs in pyramidal layer cells of rat piriform cortex: evidence for the involvement of a 5-HT2-activated interneuron. Brain Res., 506, 62–69PubMedCrossRefGoogle Scholar
  99. Shivers, B. D., Killisch, I., Sprengel, R., Sontheimer, H., Kohler, M., Schofield, P. R. and Seeburg, P. H. (1989). Two novel GABAA receptor subunits exist in distinct neuronal subpopulations. Neuron, 3, 327–337PubMedCrossRefGoogle Scholar
  100. Siegel, R. E. (1988). The mRNAs encoding GABAA/benzodiazepine receptor subunits are localized in different cell populations of the bovine cerebellum. Neuron, 1, 579–584PubMedCrossRefGoogle Scholar
  101. Singer, R. H., Bentley Lawrence, J. and Rashtchian, R. N. (1987). Toward a rapid and sensitive in situ hybridization methodology using isotopic and nonisotopic probes. In In situ Hybridization. Applications to Neurobiology. (ed. K. L. Valentino, J. H. Eberwine and J. D. Barchas). Oxford University Press, OxfordGoogle Scholar
  102. Spencer, D. G. Jr., Horváth, E. and Traber, J. (1986). Direct autoradiographic determination of Ml and M2 muscarinic acetylcholine receptor distribution in the rat brain: relation to cholinergic nuclei and projections. Brain Res., 380, 59–68PubMedCrossRefGoogle Scholar
  103. Steinbach, J. H. and Ifune, C. (1989). How many kinds of nicotinic acetylcholine receptor are there? Trends Neurosci., 12, 3–6PubMedCrossRefGoogle Scholar
  104. Stevens, C. F. (1987). Channel families in the brain. Nature, 328, 198–199PubMedCrossRefGoogle Scholar
  105. Suhanara, R. K., Niznik, H. B., Weiner., D. M., Storman, T. M., Brann, M. R., Kennedy, J. L., Gelernter, J. E., Rozmahell, R., Yang, Y., Israel, Y., Seeman, P. and O’Dowd, B. F. (1990). The human dopamine D1 receptor locus to an intronless gene on chromosome. 5 Nature, in pressGoogle Scholar
  106. Swanson, L. W., Simmons, D. M., Whiting, P. J. and Lindstrom, J. (1987). Immunohistochemical localization of neuronal nicotinic receptors in the rodent central nervous system. J. Neurosci., 7, 3334–3342PubMedGoogle Scholar
  107. Tecott, L. H., Eberwine, J. H., Barchas, J. D. and Valentino, K. L. (1987). Methodological considerations in the utilization of in situ hybridization. In In situ Hybridization. Applications to Neurobiology (ed. K. L. Valentino, J. H. Eberwine and J. D. Barchas). Oxford University Press, OxfordGoogle Scholar
  108. Unnerstall, J. R., Kuhar, M. J., Niehoff, D. L. and Palacios, J. M. (1981). Benzodiazepine receptors are coupled to a subpopulation of γ-aminobutyric acid (GABA) receptors: evidence from a quantitative autoradiographic study. J. Pharmacol. Exp. Ther., 218, 797–804PubMedGoogle Scholar
  109. Vilaró, M. T., Boddeke, H. W. G. M., Wiederhold, K.-H., Kischka, U., Mengod, G. and Palacios, J. M. (1989). Regional expression of muscarinic receptor (MChR) subtypes in rat brain: an in situ hybridization/receptor autoradiography study. Abstracts from the Fourth International Symposium on Subtypes of Muscarinic Receptors, Wiesbaden, No. 68, Trends Pharmacol. Sci. supplementGoogle Scholar
  110. Vilaró, M. T., Palacios, J. M. and Mengod, G. (1990a). Localization of m5 muscarinic receptor mRNA in rat brain examined by in situ hybridization histochemistry. Neurosci. Lett., 114, 154–159PubMedCrossRefGoogle Scholar
  111. Vilaró, M. T., Wiederhold, K.-H., Palacios, J. M. and Mengod, G. (1990b). Muscarinic cholinergic receptors in the rat caudate putamen and olfactory tubercle belong predominantly to the m4 class: In situ hybridization and receptor autoradiography evidence. Neuroscience, in pressGoogle Scholar
  112. Wada, K., Ballivet, M., Boulter, J., Connolly, J., Wada, E., Deneris, E. S., Swanson, L. W., Heinemann, S. and Patrick, J. (1988). Functional expression of a new pharmacological subtype of brain nicotinic acetylcholine receptor. Science, N. Y., 240, 330–334CrossRefGoogle Scholar
  113. Wada, K., Dechesne, C. J., Shimasaki, S., King, R. G., Kusano, K., Buonanno, A., Hampson, D. R., Banner, C., Wenthold, R. J. and Nakatani, Y. (1989). Sequence and expression of a frog brain complementary DNA encoding a kainate-binding protein. Nature, 342, 684–689PubMedCrossRefGoogle Scholar
  114. Wada, E., Wada, K., Boulter, J., Deneris, E., Heinemann, S., Patrick, J. and Swanson, L. W. (1989). Distribution of alpha2, alpha3, alpha4, and beta2 neuronal nicotinic receptor subunits mRNAs In the central nervous system: a hybridization histochemical study in the rat. J. Comp. Neurol., 284, 314–335PubMedCrossRefGoogle Scholar
  115. Watson, S. J., Sherman, T. G., Kelsey, J. E. Burke, S. and Akil, H. (1987). Anatomical localization of mRNA: in situ hybridization of neuropeptide systems. In In situ Hybridization. Applications to Neurobiology (ed. K. L. Valentino, J. H. Eberwine and J. D. Barchas), Oxford University Press, OxfordGoogle Scholar
  116. Weiner, D. M. and Brann, M. R. (1989). The distribution of a dopamine D2 receptor mRNA in rat brain. FEBS Lett., 253, 207–213PubMedCrossRefGoogle Scholar
  117. Whiting, P. J. and Lindstrom, J. M. (1986). Purification and characterization of a nicotinic acetylcholine receptor from chick brain. Biochemistry, 25, 2082–2093PubMedCrossRefGoogle Scholar
  118. Whiting, P. and Lindstrom, J. (1987). Purification and characterization of a nicotinic acetylcholine receptor from rat brain. Proc. Natl Acad. Sci. USA, 84, 595–599PubMedPubMedCentralCrossRefGoogle Scholar
  119. Wisden, W., Morris, B. J., Darlison, M. G., Hunt, S. P. and Barnard, E. A. (1988). Distinct GABAA receptor a subunit mRNAs show differential patterns of expression in bovine brain. Neuron, 1, 937–947PubMedCrossRefGoogle Scholar
  120. Wisden, W., Morris, B. J., Darlison, M. G., Hunt, S. P. and Barnard, E. A. (1989). Localization of GABAA receptor α-subunit mRNAs in relation to receptor subtypes. Molec. Brain Res., 5, 305–310PubMedCrossRefGoogle Scholar
  121. Ymer, S., Schofield, P. R., Draguhn, A., Werner, P., Kohler, M. and Seeburg, P. H. (1989). GABAA receptor β subunit heterogeneity: functional expression of cloned cDNAs. EMBO Jl, 8, 1665–1670Google Scholar
  122. Young, W. S. III and Kuhar, M. J. (1979). Autoradiographic localisation of benzodiazepine receptors in the brains of humans and animals. Nature, 280, 393–395CrossRefGoogle Scholar

Copyright information

© Macmillan Publishers Limited 1991

Authors and Affiliations

  • M. T. Vilaró
    • 1
  • M. I. Martinez-Mir
    • 1
  • M. Sarasa
    • 1
  • M. Pompeiano
    • 1
  • J. M. Palacios
    • 1
  • G. Mengod
    • 1
  1. 1.Preclinical ResearchSandoz Pharma LtdBaselSwitzerland

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