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].
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References
Aghajanian GK (1985) Modulation of a transient outward current in serotonergic neurones by α1-adrenoceptors. Nature 315: 501–503
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: 7713–7717
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: 125–141
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: 1–9
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: 279–281
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: 259–268
Barker JL, Mathers DA (1981) GABA analogues activate channels of different duration on cultured mouse spinal neurons. Science 212: 358–361
Barker JL, Ransom BR (1978) Amino acid pharmacology of mammalian central neurones grown in tissue culture. J Physiol (Lond) 280: 331–354
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: 473–482
Berridge MJ, Irvine RF (1984) Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature 312: 315–321
Braestrup C (1982) Neurotransmitters and CNS disease: anxiety. Lancet ii: 1030–1034
Brisson A, Unwin PNT (1985) Quaternary structure of the acetylcholine receptor. Nature 315: 474–477
Brown DA (1983) Slow cholinergic excitation—a mechanism for increasing neuronal excitability. Trends Neurosci 6: 302–307
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: 5871–5886
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: 313–316
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: 2843–2849
Drummond AH (1985) Bidirectional control of cytosolic free calcium by thyrotropin-releasing hormone in pituitary cells. Nature 315: 752–755
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: 5013–5017
Dunlap K, Fischbach GD (1981) Neurotransmitters decrease the calcium conductance activated by depolarisation of embryonic chick sensory neurones. J Physiol (Lond) 317: 519–535
Ewald DA, Williams A, Levitan IB (1985) Modulation of single Ca2+-dependent K+ channel activity by protein phosphorylation. Nature 315: 503–506
Gonzales RA, Crews FT (1984) Characterisation of the cholinergic stimulation of phosphoinositide hydrolysis in rat brain slices. J Neurosci 4: 3120–3127
Greengard P (1978) Phosphorylated proteins as physiological effectors. Science 199: 146–152
Hartzell HC (1981) Mechanisms of slow synaptic potentials. Nature 291: 539–544
Havrankova J, Roth J, Brownstein M (1978) Insulin receptors are widely distributed in the central nervous system of the rat. Nature 272: 827–829
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: 6692–6695
Iversen LL (1983) Neuropeptides—what next? Trends Neurosci 6: 293–294
Jan YN, Jan LY (1983) An LHRH-like peptidergic neurotrans-mitter capable of action at a distance in autonomic ganglia. Trends Neurosci 6: 320–325
Johnson M, Mitchell R, Fink G (1986) The priming effect of LHRH: is protein kinase C involved? Proc Br Endocrine Soc, April
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: 109–118
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: 4316–4320
Kelly JS (1982) Electrophysiology of peptides in the central nervous system. Br Med Bull 38: 283–290
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: 7431–7435
Levitan IB, Lemos JT, Novak-Hofer I (1983) Protein phosphorylation and the regulation of ion channels. Trends Neurosci 6: 496–499
Lundberg JM, Hokfelt T (1983) Coexistence of peptides and classical transmitters. Trends Neurosci 6: 325–333
Madison DV, Nicholl RA (1982) Noradrenaline blocks accommodation of pyramidal cell discharge in the hippocampus. Nature 299: 636–638
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: 582–584
McAllister-Williams RH, Mitchell R (1985) Benzodiazepines regulate coupling to anion channels in only some GABAa receptor complexes. Br J Pharmacol 84: 60 P
McBurney RN (1983) New approaches to the study of rapid events underlying neurotransmitter action. Trends Neurosci 6: 297–302
Michell RH (1975) Inositol phospholipids and cell surface receptor function. Biochim Biophys Acta 415: 81–147
Mitchell R, Anderson RA (1985) Antagonism by strychnine differentiates two subtypes of GABAA receptor complex. Biochem Soc Trans 13: 1216–1217
Mitchell R, Anderson RA (1985) Does an anion channel mediate the action of K opioid receptors? Regul Pept [Suppl] 4: 191–196
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 91–100
Murdoch GH, Rosenfeld MG, Evans RM (1982) Eukaryotic transcriptional regulation and chromatin-associated phosphory-lation by cyclic AMP. Science 218: 1315–1317
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 113–124
Neher E, Sakmann B (1976) Single-channel currents recorded from membrane of denervated frog muscle fibres. Nature 260: 799–802
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: 191–192
Nishizuka Y (1984) The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature 308: 693–698
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: 528–532
Nowak LM, Macdonald RL (1982) Substance P: ionic basis for depolarising responses in cell culture. J Neurosci 2: 1119–1128
Olsen RW, Fischer JB, King RG, Ransom JY, Stauber GB (1984) Purification of the GABA/benzodiazepine/barbiturate receptor complex. Neuropharmacology 23 (7B): 853–855
Oron Y, Dascal N, Nadler E, Lupu M (1985) Inositol 1,4,5-trisphosphate mimics muscarinic response in Xenopus oocytes. Nature 313: 141–143
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: 576–578
Paupardin-Tritsch D, Colombaioni L, Deterre P, Gerschenfeld HM (1985) Two different mechanisms of calcium spike modulation by dopamine. J Neurosci 5: 2522–2532
Rasmussen H, Barrett PQ (1984) Calcium messenger system—an integrated view. Physiol Rev 64: 938–984
Reuter H (1983) Calcium channel modulation by neurotransmitters, enzymes and drugs. Nature 301: 569–574
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: 1324–1331
Rink TJ, Sanchez A, Hallam TJ (1983) Diacyl glycerol and phorbol ester stimulate secretion without raising cytoplasmic free calcium in human platelets. Nature 305: 317–319
Rodbell M (1980) The role of hormone receptors and GTP-regulatory proteins in membrane transduction. Nature 284: 17–22
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: 59–60
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: 538–543
Schwartzkroin PA (1975) Characteristics of CA I neurons recorded intracellularly in the hippocampal in vitro slice preparation. Brain Res 85: 423–426
Sefton BM, Hunter T (1984) Tyrosine protein kinases. Adv Cyclic Nucleotide Protein Phosphorylation Res 18: 195–217
Siegelbaum SA, Camardo JS, Kandel ER (1982) Serotonin and cyclic AMP close single K+ channels in Aplysia sensory neurones. Nature 299: 413–417
Siegelbaum SA, Tsien RW (1983) Modulation of gated ion channels as a mode of transmitter action. Trends Neurosci 6: 307–313
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: 7219–7223
Stanfield PR, Nakajima Y, Yamaguchi K (1985) Substance P raises neuronal membrane excitability by reducing inward rectification. Nature 315: 498–501
Stevens CF (1985) Acetylcholine receptors; fivefold symmetry and the ɛ subunit. Trends Neurosci 8: 335–336
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: 67–69
Strong J A (1984) Modulation of potassium current kinetics in bag cell neurones of Aplysia by an activator of adenylate cyclase. J Neurosci 4: 2772–2783
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: 7180–7184
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: 359–361
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: 7797–7801
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: 307–314
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: 318–320
Tsien RW (1977) Cyclic AMP and contractile activity in the heart. Adv Cyclic Nucleotide Res 8: 363–420
Tsien RY, Pozzan T, Rink TJ (1982) T-cell mitogens cause early changes in cytoplasmic free Ca2+ and membrane potential in lymphocytes. Nature 295: 68–71
Tsunoo A, Konishi S, Otsuka M (1982) Substance P as an excitatory transmitter of primary afferent neurons in guineapig sympathetic ganglia. Neuroscience 7: 2025–2037
Walaas SI, Ouimet CC, Hemmings HC, Greengard P (1985) Dopamine regulated protein phosphorylation systems in the basal ganglia. Neurosci Lett [Suppl] (1985): 5409
White BA, Bauerle LR, Bancroft FC (1981) Calcium specifically stimulates prolactin synthesis and messenger RNA sequences in GH3 cells. J Biol Chem 256: 5942–5945
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: 558–561
Williams JT, Egan TM, North RA (1982) Enkephalin opens potassium channels on mammalian central neurons. Nature 299: 74–77
Witters LA, Vater CA, Lienhard GE (1985) Phosphorylation of the glucose transporter in vitro and in vivo by protein kinase C. Nature 315: 777–778
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Mitchell, R. (1987). Molecular Aspects of Central Neurotransmitter Function. In: Transmitter Molecules in the Brain. Basic and Clinical Aspects of Neuroscience, vol 2. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-69950-4_5
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DOI: https://doi.org/10.1007/978-3-642-69950-4_5
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