Skip to main content
SpringerLink
Log in

Tachykinins and excitotoxicity in cerebellar granule cells

  • Published:
The Cerebellum Aims and scope Submit manuscript

Abstract

The tachykinins represent an important group of neuropeptides that are widely distributed both in the central and peripheral nervous system where they perform several functions connected with neuronal modulation, often in synergy with glutamate excitatory transmission. While a great deal of data is available on their distribution and many studies have been performed by molecular, biochemical, and immunohistochemical techniques, much less is known about their physiological role, in particular in the cerebellum. This review is an attempt to summarize the diverse evidence suggesting a role for tachykinins in cerebellar granule neurons.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Ingi T, Kitajima Y, Minamitake Y, Nakanishi S. Characterization of ligand-binding properties and selectivities of three rat tachykinin receptors by transfection and functional expression of their cloned cDNAs in mammalian cells. J Pharmacol Exp Ther. 1991;259:968–75.

    PubMed  CAS  Google Scholar 

  2. Maggi CA. The mammalian tachykinin receptors. General Pharmacol. 1995;26:911–44.

    CAS  Google Scholar 

  3. Regoli D, Boudon A, Fauchere JL. Receptors and antagonists for substance P and related peptides. Pharmacol Rev. 1994;46:551–99.

    PubMed  CAS  Google Scholar 

  4. Longmore J, Hill RG, Hargreaves RJ. Neurokinin-receptor antagonists: Pharmacological tools and therapeutic drugs. Can. J Phys Pharm. 1997;75:612–21.

    Article  CAS  Google Scholar 

  5. Ogier R, Raggenbass M. Action of tachykinins in the rat hippocampus: Modulation of inhibitory synaptic transmission. Eur J Neurosci. 2003;17:2639–47.

    Article  PubMed  CAS  Google Scholar 

  6. Yang YL, Yao KH, Li ZW. Similarities of SP-, NKA- and NKB-induced currents in rat dorsal root ganglion neurons. Brain Res. 2003;991:18–25.

    Article  PubMed  CAS  Google Scholar 

  7. Hill RG. Substance P, opioid, and catecholamine system in the mouse central nervous system (CNS). PNAS. 2002;99:549–51.

    Article  PubMed  CAS  Google Scholar 

  8. Quartara L, Maggi CA. The tachykinin NK1 receptor. Part II: Distribution and pathophysiology roles. Neuropeptides. 1998;32:1–49.

    Article  PubMed  CAS  Google Scholar 

  9. Rupniak NM, Kramer MS. Discovery of the antidepressant and anti-emetic efficacy of substance P receptor (NK1) antagonist. Trends Pharmacol Sci. 1999;20:485–490.

    Article  PubMed  CAS  Google Scholar 

  10. Saria A. The tachykinin NK1 receptor in the brain: Pharmacology and putative functions. Eur J Pharmacol. 1999;375:51–60.

    Article  PubMed  CAS  Google Scholar 

  11. Raffa RB. Possible role(s) of neurokinins in CNS development and neurodegenerative or other disorders. Neurosci Biobehav Rev. 1998;22:789–813.

    Article  PubMed  CAS  Google Scholar 

  12. Severini C, Ciotti MT, Mercanti D, Barbato C, Calissano P. A tachykinin-like factor increases glutamate toxicity in rat cerebellar granule cells. Neuropharmacol. 2003;44:117–24.

    Article  CAS  Google Scholar 

  13. Beal MF. Mechanism of excitatory in neurologic disease. FASEBJ. 1992;6:3338–44.

    CAS  Google Scholar 

  14. Hollmann M, Heinemann S. Cloned glutamate receptors. Annu Rev Neurosci. 1994;17:31–108.

    Article  PubMed  CAS  Google Scholar 

  15. Blandini F, Porter RH, Greenamyre JT. Glutamate and Parkinson’s disease. Mol Neurobiol. 1996;12:73–94.

    Article  PubMed  CAS  Google Scholar 

  16. Lipton SA, Rosemberg PA. Excitatory amino acids as a final common pathway for neurological disorders. New Eng J Med. 1994;330:613–22.

    Article  PubMed  CAS  Google Scholar 

  17. Pieri M, Severini C, Amadoro G, et al. AMPA receptors are modulated by tachykinins in rat cerebellum neurons. J Neurophysiol. 2005;94:2484–90.

    Article  PubMed  CAS  Google Scholar 

  18. Nawa H, Kotani H, Nakanishi S. Tissue-specific generation of two preprotachykinin mRNAs from one gene by alternative RNA splicing. Nature. 1984;312:729–34.

    Article  PubMed  CAS  Google Scholar 

  19. Kotani H, Hoshimaru M, Nawa H, Nakanishi S. Structure and gene organization of bovine neuromedin K precursor. Proc Natl Acad Sci USA. 1986;83:7074–8.

    Article  PubMed  CAS  Google Scholar 

  20. MacDonald MR, McCourt DW, Krause JE. Posttranslational processing of alpha-, beta-, and gamma-preprotachykinins. Cell-free translation and early posttranslational processing events. J Biol Sci. 1988;263:15176–83.

    CAS  Google Scholar 

  21. Carter MS, Krause JE. Structure, expression, and some regulatory mechanisms of the rat preprotachykinin gene encoding substance P, neurokinin A, neuropeptide K, and neuropeptide gamma. J Neurosci. 1990;10:2203–14.

    PubMed  CAS  Google Scholar 

  22. Page NM, Woods RJ, Gardiner SM, et al. Excessive placental secretion of neurokinin B during the third trimester causes pre-eclampsia. Nature. 2000;405:797–800.

    Article  PubMed  CAS  Google Scholar 

  23. Pennefather JN, Lecci A, Candenas ML, Patak E, Pinto FM, Maggi CA. Tachykinins and tachykinin receptors: A growing family. Life Sci. 2004;74:1445–63.

    Article  PubMed  CAS  Google Scholar 

  24. Zhang Y, Lu L, Furlonger C, Wu GE, Paige CJ. Hemokinin is a hematopoietic-specific tachykinin that regulates B lymphopoiesis. Nature Immunol. 2000;1:392–7.

    Article  CAS  Google Scholar 

  25. Kurtz MM, Wang R, Clements M, et al. Identification, localization and receptor characterization of novel mammalian substance-P peptides. Gene. 2002;296:205–12.

    Article  PubMed  CAS  Google Scholar 

  26. Page NM, Woods RJ, Gardiner SM, et al. Characterization of the endokinins: Human tachykinins with cardiovascular activity. Proc Natl Acad Sci USA. 2003;100:6245–50.

    Article  PubMed  CAS  Google Scholar 

  27. Krause JE, Chirgwin JM, Carter MS, Xu ZS, Hershey AD. Three rat reprotachykinin mRNAs encode the neuropeptides substance P and neurokinin A. Proc Natl Acad Sci USA. 1987;84:881–5.

    Article  PubMed  CAS  Google Scholar 

  28. Holmgren S, Jensen J. Evolution of vertebrate neuropeptides. Brain Res Bull. 2001;55:723–35.

    Article  PubMed  CAS  Google Scholar 

  29. Harrison S, Geppetti P. Substance P. Int J Biochem Cell Biol. 2001;33:555–76.

    Article  PubMed  CAS  Google Scholar 

  30. Severini C, Improta G, Falconieri-Erspamer G, Salvatori S, Erspamer V. The tachykinin peptide family. Pharmacol Rev. 2002;54:1–38.

    Article  Google Scholar 

  31. Hokfelt T, Holets VR, Staines W, et al. Coexistence of neuronal messengers: An overview. Prog Brain Res. 1986;68:33–70.

    Article  PubMed  CAS  Google Scholar 

  32. Otsuka M, Yoshioka K. Neurotransmitter functions of mammalian tachykinins. Physiol Rev. 1993;73:229–308.

    PubMed  CAS  Google Scholar 

  33. Page NM. Hemokinins and endokinins. Cell Mol Life Sci. 2004;61:1652–63.

    Article  PubMed  CAS  Google Scholar 

  34. Tsukida K, Shigemoto R, Yokota Y, Nakanishi S. Tissue distribution and quantitation of the mRNAs for the three rat tachykinin receptors. Eur J Biochem. 1990;193:751–7.

    Article  Google Scholar 

  35. Merchenthaler I, Maderdrut JL, O’Harte F, Conlon JM. Localization of neurokinin B in the central nervous system of the rat. Peptides. 1992;13:815–29.

    Article  PubMed  CAS  Google Scholar 

  36. Kaneko T, Murashima M, Lee T, Mizuno N. Characterization of neocortical non-pyramidal neurons expressing preprotachykinin A and B: a double immunofluorescence study in the rat. Neuroscience. 1998;86:765–81.

    Article  PubMed  CAS  Google Scholar 

  37. Maggi CA. Principles of tachykininergic co-transmission in the peripheral and enteric nervous system. Regul Peptides. 2000;93:53–64.

    Article  CAS  Google Scholar 

  38. Barbato C, Ciotti MT, Serafino A, Severini C, Calissano P. Tachykinin neuropeptides in cerebellar granule neurons: an immunocytochemical study. Eur J Histochem. 2005;49:87–92.

    PubMed  CAS  Google Scholar 

  39. Aita M, Seo K, Fujiwara N, Takagi R, Maeda T. Postnatal changes in the spatial distributions of substance P and NK1 receptor in the trigeminal subnucleus caudalis of mice. Brain Res Dev Brain Res. 2005;155:33–41.

    Article  PubMed  CAS  Google Scholar 

  40. Baloyannis SJ, Costa V, Deretzi G, Michmizos D. Intraventricular administration of substance P increases the dendritic arborisation and the synaptic surfaces of Purkinje cells in rat’s cerebellum. Int J Neurosci. 2000;101:89–107.

    Article  PubMed  CAS  Google Scholar 

  41. Mussap CJ, Geraghty DP, Burcher E. Tachykinin receptors: A radioligand binding perspective. J Neurochem. 1993;60:1987–2009.

    Article  PubMed  CAS  Google Scholar 

  42. Krause JE, Blount P, Sachais BS. Molecular biology of receptors. Structure., expression and regulatory mechanisms. In: Buck SH, editor. The tachykinin receptors. New York: Humana Press; 1994. pp 165–218.

    Google Scholar 

  43. Guard S, Watson SP. Tachykinin receptor types: Classification membrane signalling mechanism. Neurochem Int. 1991;18:149–65.

    Article  CAS  Google Scholar 

  44. Takeda Y, Blount P, Sachais BS, Hershey AD, Raddatz R, Krause JE. Ligand binding kinetics of substance P and neurokinin A receptors stably expressed in Chinese hamster ovary cells and evidence for differential stimulation of inositol 1,4,5-trisphosphate and cyclic AMP second messenger responses. J Neurochem. 1992;59:740–5.

    Article  PubMed  CAS  Google Scholar 

  45. Mochizuki-Oda N, Nakajima Y, Nakanishi S, Ito S. Characterization of the substance P receptor-mediated calcium influx in cDNA transfected Chinese hamster ovary cells. A possible role of inositol 1,4,5-trisphosphate in calcium influx. J Biol Chem. 1994;269:9651–8.

    PubMed  CAS  Google Scholar 

  46. Nakajima Y, Tsukida K, Nagishi M, Ito S, Nakanishi S. Direct linkage of three tachykinin receptors to stimulation of both phosphatidylinositol hydrolysis and cyclic AMP cascades in transfected Chinese hamster ovary cells. J Biol Sci. 1992;267:2437–42.

    CAS  Google Scholar 

  47. Palanche T, Ilien B, Zoffmann S, et al. The neurokinin A receptor activates calcium and cAMP responses through distinct conformational states. J Biol Chem. 2001;276:34853–61.

    Article  PubMed  CAS  Google Scholar 

  48. Stumm R, Culmsee C, Schafer MKH, Krieglstein J, Wheihe E. Adaptative plasticity in tachykinin receptor expression after focal cerebral ischemia is differentially linked to GABAergic and glutamatergic cerebrocortical circuits and cerebrovenular endothelium. J Neurosci. 2001;21:798–811.

    PubMed  CAS  Google Scholar 

  49. Dingledine R, Borges K, Bowie D, Traynelis SF. The glutamate receptors ion channels. Pharmacol Rev. 1999;51:7–61.

    PubMed  CAS  Google Scholar 

  50. Limatola C. Neurotrophic effects of AMPA. Cerebellum. 2003;2:2–10.

    Article  Google Scholar 

  51. Schwarzer C, Williamson JM, Lothman EW, Vezzani A, Sperk G. Somatostatin, neuropeptide Y, neurokinin B and cholecystokinin immunoreactivity in two chronic models of temporal lobe epilepsy. Neurosci. 1995;69:831–45.

    Article  CAS  Google Scholar 

  52. Liu H, Mazarati AM, Katsumori H, Sankar R, Wasterlain CG. Substance P is expressed in hippocampal principal neurons during status epilepticus and plays a critical role in the maintenance of status epilepticus. PNAS. 1999;96:5286–91.

    Article  PubMed  CAS  Google Scholar 

  53. Maubach KA, Cody C, Jones RSG. Tachykinins may modify spontaneous epileptiform activity in the rat entorhinal cortex in vitro by activating GABAergic inhibition. Neurosci. 1998;83:1047–62.

    Article  CAS  Google Scholar 

  54. Marksteiner J, Wahler R, Bellmann R, Ortler M, Krause JE, Sperk G. Limbic seizures cause pronounced changes in the expression of neurokinin B in the hippocampus of the rat. Neurosci. 1992;49:383–95.

    Article  CAS  Google Scholar 

  55. Bailey CP, Maubach KA, Jones RSG. Neurokinin-1 receptors in the rat nucleus tractus solitarius: pre- and postsynaptic modulation of glutamate and GABA release. Neurosci. 2004;127:467–79. 56. Shen KZ, North RA. Substance P opens cation channels and closes potassium channels in rat locus coeruleus neurons. Neurosci. 1992;50:345–53.

    Article  CAS  Google Scholar 

  56. Bell MI, Richardson PJ, Lee K. Characterization of the mechanism of action of tachykinins in rat striatal cholinergic interneurons. Neurosci. 1998;87:649–58.

    Article  CAS  Google Scholar 

  57. Sculptoreanu A, de Groat W. Protein kinase C is involved in neurokinin receptor modulation of N- and L-type Ca2+ channels in DRG Neurons of the adult rat. J Neurophysiol. 2003;90:21–31.

    Article  PubMed  CAS  Google Scholar 

  58. Barker R. Tachykinins, neurotrophism and neurodegenerative disorders: A critical review on the possible role of tachykinins in the aetiology of CNS disease. Rev Neurosci. 1996;7:187–214.

    PubMed  CAS  Google Scholar 

  59. Kemel ML, Perez S, Godeheu G, Soubrie P, Glowinski J. Facilitation by endogenous tachykinins of the NMDA-evoked release of acetylcholine after acute and chronic suppression of dopaminergic transmission in the matrix of the rat striatum. J Neurosci. 2002;22:1929–36.

    PubMed  CAS  Google Scholar 

  60. Chizh BA, Cumberbatch MJ, Birch PJ, Headley PM. Endogenous modulation of excitatory amino acid responsiveness by tachykinin NK1 and NK2 receptors in the rat spinal cord. Br J Pharmacol. 1995;115:1013–19.

    PubMed  CAS  Google Scholar 

  61. Kouznetsova M, Nistri A. Modulation by substance P of synaptic transmission in the mouse hippocampal slice. Eur J Neurosci. 1998;10:3076–84.

    Article  PubMed  CAS  Google Scholar 

  62. Burnashev N, Monyer H, Seeburg PH, Sakmann B. Divalent ion permeability of AMPA receptor channels is dominated by the edited form of a single subunit. Neuron. 1992;8:189–98.

    Article  PubMed  CAS  Google Scholar 

  63. Geiger JR, Melcher T, Koh DS, et al. Relative abundance of subunit mRNAs determines gating and Ca2+ permeability of AMPA receptors in principal neurons and interneurons in rat CNS. Neuron. 1995;15:193–204.

    Article  PubMed  CAS  Google Scholar 

  64. Vanderberghe W, Robberecht W, Brorson JR. AMPA receptor calcium permeability, GluR2 expression, and selective motoneuron vulnerability. J Neurosci. 2000;20:123–32.

    Google Scholar 

  65. Weiss JH, Sensi SL. Ca2+-Zn2+ permeable AMPA or kainate receptor: possible key factors in selective neurodegeneration. Trends Neurosci. 2000;23:365–71.

    Article  PubMed  CAS  Google Scholar 

  66. Liu S, Lau L, Wei J, Zhu D, Zou S, Sun HS, Fu Y, Liu F, Lu Y. Expression of Ca(2+)-permeable AMPA receptor channels primes cell death in transient forebrain ischemia. Neuron. 2004;43:43–55.

    Article  PubMed  Google Scholar 

  67. Balojannis SJ, Costa V, Deretzi G, Michmizos D. Intraventricular administration of Substance P increases the dendritic arborisation and the synaptic surfaces of Purkinje cells in rat’s cerebellum. Int J Neurosci. 2000;101:89–107.

    Article  Google Scholar 

  68. Yacubova E, Komuro H. Intrinsic program for migration of cerebellar granule cells in vitro. J Neurosci. 2002;22:5966–81.

    PubMed  CAS  Google Scholar 

  69. Wetts R, Herrup K. Direct correlation between Purkinje and granule cell number in the cerebella of lurcher chimeras and wild-type mice. Brain Res. 1983;312:41–7.

    PubMed  CAS  Google Scholar 

  70. Oppenheim RW. Cell death during the development of the nervous system. Annu Rev Neurosci. 1991;14:453–501.

    Article  PubMed  CAS  Google Scholar 

  71. Altmann J. Morphological development of the rat cerebellum and some of its mechanisms. Exp Brain Res. 1982;6:8–49.

    Google Scholar 

  72. Inagaki S, Sakanaka M, Shiosaka S, Senba E, Takagi H, Takatsuki K, Kawai Y, Matsuzaki T, Iida H, Hara Y, Tohyama M. Experimental and immunohistochemical studies on the cerebellar substance P of the rat: Localization, postnatal ontogeny and ways of entry to the cerebellum. Neuroscience. 1982;7:639–45.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Neurobiology and Molecular Medicine, Rome, Italy

    Cinzia Severini

  2. Fondazione S. Lucia, CERC, Italy

    Cinzia Severini & Cristina Zona

  3. Department of Neuroscience, University of Rome “Tor Vergata”, Via Montpellier, 100133, Rome, Italy

    Cristina Zona

Authors
  1. Cinzia Severini
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cristina Zona
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Cristina Zona.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Severini, C., Zona, C. Tachykinins and excitotoxicity in cerebellar granule cells. Cerebellum 5, 232–237 (2006). https://doi.org/10.1080/14734220600673295

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1080/14734220600673295

Key words

Search

Navigation