Advertisement

Molecular Aspects of Central Neurotransmitter Function

  • Rory Mitchell
Conference paper
Part of the Basic and Clinical Aspects of Neuroscience book series (BASIC, volume 2)

Abstract

It is clear from the previous chapters that the list of substances that may be considered as possible neurotransmitters in the central nervous system is rapidly growing. In addition to the now ‘classical’ neurotransmitters such as acetylcholine, monoamines and amino acids (amongst which there are also new tentative candidates such as adrenaline and taurine), there are now scores of neuropeptide candidates. Few of these have been shown to fully satisfy the criteria for acceptance as neurotransmitters. Nevertheless, in many cases there is evidence fully consistent with, and suggestive of, a role in chemical neurotransmission. A general impression has developed that neural actions of peptides are inordinately slow in onset and offset and that they should therefore be regarded more as long-term neuromodulators than as true transmitters. This may relate in part to our limited ability to rapidly deliver adequate concentrations of peptides to the correct neuronal loci, due to factors such as poor ejection from micropipettes and the presence of powerful peptide-degrading enzymes in neuronal tissue [31].

Keywords

Phorbol Ester Neurotransmitter Action GABAA Receptor Complex Slow Depolarisation Clonal Pituitary Cell 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Aghajanian GK (1985) Modulation of a transient outward current in serotonergic neurones by α1-adrenoceptors. Nature 315: 501–503PubMedCrossRefGoogle Scholar
  2. 2.
    Albert KA, Helmer-Matyjek E, Nairn AC, Muller TH, Haycock JW, Greene LA, Goldstein M, Greengard P (1984) Calcium/ phospholipid-dependent protein kinase (protein kinase C) phosphorylates and activates tyrosine hydroxylase. Proc Natl Acad Sci USA 81: 7713–7717PubMedCrossRefGoogle Scholar
  3. 3.
    Alger BE, Nicoll RA (1982) Pharmacological evidence for two kinds of GABA receptor on rat hippocampal pyramidal cells studied in vitro. J Physiol (Lond) 328: 125–141Google Scholar
  4. 4.
    Anderson RA, Mitchell R (1986) Biphasic effect of GABAA receptor agonists on prolactin secretion: evidence for two types of GABAA receptor complex on lactotrophes. Eur J Pharmacol 124: 1–9PubMedCrossRefGoogle Scholar
  5. 5.
    Barinaga M, Bilezikjian LM, Vale WW, Rosenfeld MG, Evans RM (1985) Independent effects of growth hormone releasing factor on growth hormone release and gene transcription. Nature 314: 279–281PubMedCrossRefGoogle Scholar
  6. 6.
    Barker JL, Dufy B, Owen D, Segal M (1983) Excitable membrane properties of cultured CNS neurons and clonal pituitary cells. Cold Spring Harbor Symp Quant Biol 48: 259–268PubMedGoogle Scholar
  7. 7.
    Barker JL, Mathers DA (1981) GABA analogues activate channels of different duration on cultured mouse spinal neurons. Science 212: 358–361PubMedCrossRefGoogle Scholar
  8. 8.
    Barker JL, Ransom BR (1978) Amino acid pharmacology of mammalian central neurones grown in tissue culture. J Physiol (Lond) 280: 331–354Google Scholar
  9. 9.
    Berridge MJ, Dawson RMC, Downes CP, Heslop JP, Irvine RF (1983) Changes in the levels of inositol phosphates after agonist-dependent hydrolysis of membrane phospholipids. Biochem J 212: 473–482PubMedGoogle Scholar
  10. 10.
    Berridge MJ, Irvine RF (1984) Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature 312: 315–321PubMedCrossRefGoogle Scholar
  11. 11.
    Braestrup C (1982) Neurotransmitters and CNS disease: anxiety. Lancet ii: 1030–1034CrossRefGoogle Scholar
  12. 12.
    Brisson A, Unwin PNT (1985) Quaternary structure of the acetylcholine receptor. Nature 315: 474–477PubMedCrossRefGoogle Scholar
  13. 13.
    Brown DA (1983) Slow cholinergic excitation—a mechanism for increasing neuronal excitability. Trends Neurosci 6: 302–307CrossRefGoogle Scholar
  14. 14.
    Codina J, Hildebrandt JD, Sekura RD, Birnbaumer M, Bryan J, Manclark R, Iyengar R, Birnbaumer L (1984) Ns and Ni? the stimulatory and inhibitory regulatory components of adenyl cyclases: purification of the human erythrocyte proteins without the use of activating regulatory ligands. J Biol Chem 259: 5871–5886PubMedGoogle Scholar
  15. 15.
    DeRiemer SA, Strong JA, Albert KA, Greengard P, Kaczmarek LK (1985) Enhancement of calcium current in Aplysia neurones by phorbolester and protein kinase C. Nature 313: 313–316PubMedCrossRefGoogle Scholar
  16. 16.
    Detre JA, Nairn AC, Aswad DW, Greengard P (1984) Localization in mammalian brain of G-substrate, a specific substrate for guanosine 3′,5′-cyclic monophosphate-dependent protein kinase. J Neurosci 4: 2843–2849PubMedGoogle Scholar
  17. 17.
    Drummond AH (1985) Bidirectional control of cytosolic free calcium by thyrotropin-releasing hormone in pituitary cells. Nature 315: 752–755PubMedCrossRefGoogle Scholar
  18. 18.
    Drummond AH, Benson JA, Levitan IE (1980) Serotonin-induced hyperpolarisation of an identified Aplysia neuron is mediated by cyclic AMP. Proc Natl Acad Sci USA 77: 5013–5017PubMedCrossRefGoogle Scholar
  19. 19.
    Dunlap K, Fischbach GD (1981) Neurotransmitters decrease the calcium conductance activated by depolarisation of embryonic chick sensory neurones. J Physiol (Lond) 317: 519–535Google Scholar
  20. 20.
    Ewald DA, Williams A, Levitan IB (1985) Modulation of single Ca2+-dependent K+ channel activity by protein phosphorylation. Nature 315: 503–506PubMedCrossRefGoogle Scholar
  21. 21.
    Gonzales RA, Crews FT (1984) Characterisation of the cholinergic stimulation of phosphoinositide hydrolysis in rat brain slices. J Neurosci 4: 3120–3127PubMedGoogle Scholar
  22. 22.
    Greengard P (1978) Phosphorylated proteins as physiological effectors. Science 199: 146–152PubMedCrossRefGoogle Scholar
  23. 23.
    Hartzell HC (1981) Mechanisms of slow synaptic potentials. Nature 291: 539–544PubMedCrossRefGoogle Scholar
  24. 24.
    Havrankova J, Roth J, Brownstein M (1978) Insulin receptors are widely distributed in the central nervous system of the rat. Nature 272: 827–829PubMedCrossRefGoogle Scholar
  25. 25.
    Hazum E, Cuatrecasas P, Marian J, Conn PM (1980) Receptor-mediated internalisation of fluorescent gonadotropin-releasing hormone by pituitary gonadotropes. Proc Natl Acad Sci USA 77: 6692–6695PubMedCrossRefGoogle Scholar
  26. 26.
    Iversen LL (1983) Neuropeptides—what next? Trends Neurosci 6: 293–294CrossRefGoogle Scholar
  27. 27.
    Jan YN, Jan LY (1983) An LHRH-like peptidergic neurotrans-mitter capable of action at a distance in autonomic ganglia. Trends Neurosci 6: 320–325CrossRefGoogle Scholar
  28. 28.
    Johnson M, Mitchell R, Fink G (1986) The priming effect of LHRH: is protein kinase C involved? Proc Br Endocrine Soc, AprilGoogle Scholar
  29. 29.
    Kaczorowski GJ, Vandlen RL, Katz GM, Reuben JP (1983) Regulation of excitation-secretion coupling by thyrotropin-releasing hormone (TRH): evidence for TRH receptor-ion channel coupling in cultured pituitary cells. J Membr Biol 71: 109–118PubMedCrossRefGoogle Scholar
  30. 30.
    Kelleher DJ, Pessin JE, Ruoho AE, Johnson GL (1984) Phorbolester induces desensitisation of adenylate cyclase and phosphorylation of the β-adrenergic receptor in turkey erythrocytes. Proc Natl Acad Sci USA 81: 4316–4320PubMedCrossRefGoogle Scholar
  31. 31.
    Kelly JS (1982) Electrophysiology of peptides in the central nervous system. Br Med Bull 38: 283–290PubMedGoogle Scholar
  32. 32.
    Lapetina EG, Watson SP, Cuatrecasas P (1984) Myo-inositol 1,4,5-triphosphate stimulates protein phosphorylation in saponin-permeabilised human platelets. Proc Natl Acad Sci USA 81: 7431–7435PubMedCrossRefGoogle Scholar
  33. 33.
    Levitan IB, Lemos JT, Novak-Hofer I (1983) Protein phosphorylation and the regulation of ion channels. Trends Neurosci 6: 496–499CrossRefGoogle Scholar
  34. 34.
    Lundberg JM, Hokfelt T (1983) Coexistence of peptides and classical transmitters. Trends Neurosci 6: 325–333CrossRefGoogle Scholar
  35. 35.
    Madison DV, Nicholl RA (1982) Noradrenaline blocks accommodation of pyramidal cell discharge in the hippocampus. Nature 299: 636–638PubMedCrossRefGoogle Scholar
  36. 36.
    Matthews HR, Torre V, Lamb TD (1985) Effects on the photoresponse of calcium buffers and cyclic GMP incorporated into the cytoplasm of retinal rods. Nature 313: 582–584PubMedCrossRefGoogle Scholar
  37. 37.
    McAllister-Williams RH, Mitchell R (1985) Benzodiazepines regulate coupling to anion channels in only some GABAa receptor complexes. Br J Pharmacol 84: 60 PGoogle Scholar
  38. 38.
    McBurney RN (1983) New approaches to the study of rapid events underlying neurotransmitter action. Trends Neurosci 6: 297–302CrossRefGoogle Scholar
  39. 39.
    Michell RH (1975) Inositol phospholipids and cell surface receptor function. Biochim Biophys Acta 415: 81–147PubMedGoogle Scholar
  40. 40.
    Mitchell R, Anderson RA (1985) Antagonism by strychnine differentiates two subtypes of GABAA receptor complex. Biochem Soc Trans 13: 1216–1217Google Scholar
  41. 41.
    Mitchell R, Anderson RA (1985) Does an anion channel mediate the action of K opioid receptors? Regul Pept [Suppl] 4: 191–196Google Scholar
  42. 42.
    Mitchell R, Ogier S-A, Johnson M, Cleland A, Bennie J, Fink G (1986) Evidence for sex differences in GnRH receptors and mechanism of action. In: Neuroendocrine molecular biology. Ed: Fink G, Harmar AJ & McKerns KW Plenum, London, pp 91–100Google Scholar
  43. 43.
    Murdoch GH, Rosenfeld MG, Evans RM (1982) Eukaryotic transcriptional regulation and chromatin-associated phosphory-lation by cyclic AMP. Science 218: 1315–1317PubMedCrossRefGoogle Scholar
  44. 44.
    Naor Z, Amsterdam A, Catt KJ (1984) Binding and activation of gondadotropin-releasing hormone receptors in pituitary gonadotropes. In: Hormone receptors in growth and reproduction. Ed: Fink G, Harmar AJ & McKerns KW Raven, New York, pp 113–124Google Scholar
  45. 45.
    Neher E, Sakmann B (1976) Single-channel currents recorded from membrane of denervated frog muscle fibres. Nature 260: 799–802PubMedCrossRefGoogle Scholar
  46. 46.
    Newberry NR, Priestley T, Woodruff GN (1985) Pharmacological distinction between two muscarinic responses on the isolated superior cervical ganglion of the rat. Eur J Pharmacol 116: 191–192PubMedCrossRefGoogle Scholar
  47. 47.
    Nishizuka Y (1984) The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature 308: 693–698PubMedCrossRefGoogle Scholar
  48. 48.
    Noda M, Takahashi H, Tanabe T, Toyosato M, Kikyotani S, Furutani Y, Hirose T, Takashima H, Inayama S, Miyata T, Numa S (1983) Structural homology of Torpedo californica acetylcholine receptor subunits. Nature 302: 528–532PubMedCrossRefGoogle Scholar
  49. 49.
    Nowak LM, Macdonald RL (1982) Substance P: ionic basis for depolarising responses in cell culture. J Neurosci 2: 1119–1128PubMedGoogle Scholar
  50. 50.
    Olsen RW, Fischer JB, King RG, Ransom JY, Stauber GB (1984) Purification of the GABA/benzodiazepine/barbiturate receptor complex. Neuropharmacology 23 (7B): 853–855CrossRefGoogle Scholar
  51. 51.
    Oron Y, Dascal N, Nadler E, Lupu M (1985) Inositol 1,4,5-trisphosphate mimics muscarinic response in Xenopus oocytes. Nature 313: 141–143PubMedCrossRefGoogle Scholar
  52. 52.
    Osterreider W, Brum G, Hescheler J, Trautwein W, Flockerzi V, Hofmann F (1982) Injection of subunits of cyclic AMP-dependent protein kinase into cardiac myocytes modulates Ca2+ current. Nature 298: 576–578CrossRefGoogle Scholar
  53. 53.
    Paupardin-Tritsch D, Colombaioni L, Deterre P, Gerschenfeld HM (1985) Two different mechanisms of calcium spike modulation by dopamine. J Neurosci 5: 2522–2532PubMedGoogle Scholar
  54. 54.
    Rasmussen H, Barrett PQ (1984) Calcium messenger system—an integrated view. Physiol Rev 64: 938–984PubMedGoogle Scholar
  55. 55.
    Reuter H (1983) Calcium channel modulation by neurotransmitters, enzymes and drugs. Nature 301: 569–574PubMedCrossRefGoogle Scholar
  56. 56.
    Reyl-Desmars F, Lewin MJM (1982) Evidence for an intracellular somatostatin receptor in pancreas: a comparative study with reference to gastric mucosa. Biochem Biophys Res Comm 109: 1324–1331PubMedCrossRefGoogle Scholar
  57. 57.
    Rink TJ, Sanchez A, Hallam TJ (1983) Diacyl glycerol and phorbol ester stimulate secretion without raising cytoplasmic free calcium in human platelets. Nature 305: 317–319PubMedCrossRefGoogle Scholar
  58. 58.
    Rodbell M (1980) The role of hormone receptors and GTP-regulatory proteins in membrane transduction. Nature 284: 17–22PubMedCrossRefGoogle Scholar
  59. 59.
    Sagi-Eisenberg R, Lieman H, Pecht I (1985) Protein kinase C regulation of the receptor-coupled calcium signal in histamine-secreting rat basophilic leukaemia cells. Nature 313: 59–60PubMedCrossRefGoogle Scholar
  60. 60.
    Sakmann B, Methfessel C, Mishina M, Takahashi T, Takai T, Kurasaki M, Fukuda K, Numa S (1985) Role of acetylcholine receptor subunits in gating of the channel. Nature 318: 538–543PubMedCrossRefGoogle Scholar
  61. 61.
    Schwartzkroin PA (1975) Characteristics of CA I neurons recorded intracellularly in the hippocampal in vitro slice preparation. Brain Res 85: 423–426PubMedCrossRefGoogle Scholar
  62. 62.
    Sefton BM, Hunter T (1984) Tyrosine protein kinases. Adv Cyclic Nucleotide Protein Phosphorylation Res 18: 195–217PubMedGoogle Scholar
  63. 63.
    Siegelbaum SA, Camardo JS, Kandel ER (1982) Serotonin and cyclic AMP close single K+ channels in Aplysia sensory neurones. Nature 299: 413–417PubMedCrossRefGoogle Scholar
  64. 64.
    Siegelbaum SA, Tsien RW (1983) Modulation of gated ion channels as a mode of transmitter action. Trends Neurosci 6: 307–313CrossRefGoogle Scholar
  65. 65.
    Sigel E, Barnard EA (1984) A α-aminobutyric acid/benxodiazepine receptor complex from bovine cerebral cortex: improved purification with preservation of regulatory sites and their interactions. J Biol Chem 259: 7219–7223PubMedGoogle Scholar
  66. 66.
    Stanfield PR, Nakajima Y, Yamaguchi K (1985) Substance P raises neuronal membrane excitability by reducing inward rectification. Nature 315: 498–501PubMedCrossRefGoogle Scholar
  67. 67.
    Stevens CF (1985) Acetylcholine receptors; fivefold symmetry and the ɛ subunit. Trends Neurosci 8: 335–336CrossRefGoogle Scholar
  68. 68.
    Streb H, Irvine RF, Berridge MJ, Schulz I (1983) Release of Ca2+ from a non-mitochondrial intracellular store in pancreatic acinar cells by inositol-l,4,5-trisphosphate. Nature 306: 67–69PubMedCrossRefGoogle Scholar
  69. 69.
    Strong J A (1984) Modulation of potassium current kinetics in bag cell neurones of Aplysia by an activator of adenylate cyclase. J Neurosci 4: 2772–2783PubMedGoogle Scholar
  70. 70.
    Study RE, Barker JL (1981) Diazepam and (−) pentobarbital: fluctuation analysis reveals different mechanisms for potentiation of α-aminobutyric acid responses in cultured central neurones. Proc Natl Acad Sci USA 78: 7180–7184PubMedCrossRefGoogle Scholar
  71. 71.
    Sugden D, Vanecek J, Klein DC, Thomas TP, Anderson WB (1985) Activation of protein kinase C potentiates isoprenaline-induced cyclic AMP accumulation in rat pinealocytes. Nature 314: 359–361PubMedCrossRefGoogle Scholar
  72. 72.
    Takayama S, White MF, Lauris V, Kahn CR (1984) Phorbol es-ters modulate insulin receptor phosphorylation and insulin action in cultured hepatoma cells. Proc Natl Acad Sci USA 81: 7797–7801PubMedCrossRefGoogle Scholar
  73. 73.
    Trautwein W, Taniguchi J, Noma A (1982) The effects of intracellular cyclic nucleotide and calcium on the action potential and acetylcholine response of isolated cardiac cells. Pflügers Arch 392: 307–314PubMedCrossRefGoogle Scholar
  74. 74.
    Truneh A, Albert F, Golstein P, Schmitt-Verhulst A-M (1985) Early steps of lymphocyte activation bypassed by synergy between calcium ionophores and phorbolester. Nature 313: 318–320PubMedCrossRefGoogle Scholar
  75. 75.
    Tsien RW (1977) Cyclic AMP and contractile activity in the heart. Adv Cyclic Nucleotide Res 8: 363–420PubMedGoogle Scholar
  76. 76.
    Tsien RY, Pozzan T, Rink TJ (1982) T-cell mitogens cause early changes in cytoplasmic free Ca2+ and membrane potential in lymphocytes. Nature 295: 68–71PubMedCrossRefGoogle Scholar
  77. 77.
    Tsunoo A, Konishi S, Otsuka M (1982) Substance P as an excitatory transmitter of primary afferent neurons in guineapig sympathetic ganglia. Neuroscience 7: 2025–2037PubMedCrossRefGoogle Scholar
  78. 78.
    Walaas SI, Ouimet CC, Hemmings HC, Greengard P (1985) Dopamine regulated protein phosphorylation systems in the basal ganglia. Neurosci Lett [Suppl] (1985): 5409Google Scholar
  79. 79.
    White BA, Bauerle LR, Bancroft FC (1981) Calcium specifically stimulates prolactin synthesis and messenger RNA sequences in GH3 cells. J Biol Chem 256: 5942–5945PubMedGoogle Scholar
  80. 80.
    Williams DA, Fogarty KE, Tsien RY, Fay FS (1985) Calcium gradients in single smooth muscle cells revealed by the digital imaging microscope using Fura-II. Nature 318: 558–561PubMedCrossRefGoogle Scholar
  81. 81.
    Williams JT, Egan TM, North RA (1982) Enkephalin opens potassium channels on mammalian central neurons. Nature 299: 74–77PubMedCrossRefGoogle Scholar
  82. 82.
    Witters LA, Vater CA, Lienhard GE (1985) Phosphorylation of the glucose transporter in vitro and in vivo by protein kinase C. Nature 315: 777–778PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1987

Authors and Affiliations

  • Rory Mitchell
    • 1
  1. 1.MRC Brain Metabolism Unit, Department of PharmacologyUniversity of EdinburghEdinburghUK

Personalised recommendations