The Involvement of Protein kinase C in Glutamate-Mediated Nociceptive Response at the Spinal Cord of Rats

흰쥐의 척수에서 Glutamate가 매개하는 Nociceptive Response에 있어서 Protein kinase C의 관련성

  • 김성정 (중앙대학교 약학대학 약리학교실) ;
  • 박전희 (중앙대학교 약학대학 약리학교실) ;
  • 이영욱 (중앙대학교 약학대학 약리학교실) ;
  • 양성준 (중앙대학교 약학대학 약리학교실) ;
  • 이종은 (중앙대학교 약학대학 약리학교실) ;
  • 이병천 (중앙대학교 약학대학 약리학교실) ;
  • 손의동 (중앙대학교 약학대학 약리학교실) ;
  • 허인회 (중앙대학교 약학대학 약리학교실)
  • Published : 1999.04.01

Abstract

When glutamate was infected intrathecally, the result is similar to those produced by TPA injected. The involvement of protein kinase C (PKC) in the nociceptive responses in rat dorsal horn neurons of lumbar spinal cord was studied. In test with formalin, a PKC inhibitor (chelerythrine) inhibited dose-dependently the formalin-induced behavior response. Neomycin also inhibited it significantly. But, a PKC activator (12-O-tetradecanoylphorbol-13-ester, TPA) showed reverse effect. When gluatamate was injected intrathecally, we observed the result is smilar to those produced by TPA injection. On the other hand, intrathecal injection of glutamate induced thermal and mechanical hyperalgesia. In Tail-flick test, we examined the involvement of PKC on the glutamate-indeced thermal hyperalgesia. Chelerythrine showed an inhibitory effect and TPA enhanced thermal response. Glutamate decreased the mechanical threshold significantly. A pretreatment of chelerythrine and neomycin inhibited glutamate-induced mechanical hyperalgesia, but the effect of neomycin was not significant. TPA had little effect on the mechanical nociceptive response. These results suggest that the PKC activation through metabotropic receptor at postsynaptic region of spinal cord dorsal horn neurons may influence on the persistent nociception produced by chemical stimulation with formalin, thermal and mechanical hyperalgesia induced by glutamate.

Keywords

References

  1. Trends. Pharmacol. Sci. v.11 Excitatory amino acid receptors and synaptic plasticity Collingridge, G. L.;Singer, W.
  2. Curr. Opin. Neurobiol. v.3 The pharmacology of pain signalling Zieglgansberber, W.;Tolle, T. R.
  3. Eur. J. Neurosci. v.6 Requirement of metabtropic glutamate receptors for the generation of inflammation-evoked hyperexcitability in rat spinal cord neurons Neugebauer, V.;Lucke, T.;Schaible, H. G.
  4. Brain Res. v.29 Modulation of glutamate receptors: molecular mechanisms and fuctional implications Sroblewski, J. T.;Danysz, W.
  5. Pharmacol. Rev. v.40 Excitatory amino acid receptors in the vetebrate central nervous system Collingride, G. L.;Lester, R. A. J.
  6. Pain. v.62 Mechanisms of hyperalgesia and mophine tolerance : a current view of their possible interactions Mao, J.;Price D. D.;Mayer, D. J.
  7. Annu. Rev. Biochem. v.56 Inositol triphosphate and diacylglycerol: Two interacting second messengers Berridge, M. J.
  8. Neurosci. Lett. v.144 Modulation of AMPA and NMDA responses in rat spinal dorsal horn neurons by trans-1-aminocyclopentane-1,3-dicarboxylic acid Cerne, R.;Randic, M.
  9. Pain v.56 The effect of t-ACPD, a metabotropic excitatory amino acid receptor agonist, on the responses of primate spinothalamic tract neurons Palecek, J.;Paleckova, V.;Dougherty, P. M.;Willis, W. D.
  10. Neuropharmacology v.36 no.8 Potentiation of NMDA and AMPA Responses by Group I mGlu R in spinal cord motoneurons Ugolini, A.;Corsi, M.;Bordi, F.
  11. Brain. Res. v.584 Intrathecal GM1 ganglioside and local nerve anesthesia reduce nociceptive behaviors in rats with experimental peripheral mononeuropathy Mao, J.;Price, D. D.;Hayes, R. L.;Lu, J.;Mayer, D. J.
  12. J. Neurosci. v.6 Heterogeneous localization of protein kinase C in rat brain : autoradiographic analysis of phorbol ester receptor binding Worley, P. F.;Baraban, J. M.;Snyder, S. H.
  13. Brain Res. v.588 Pain-related increase in spinal cord membrane-bound Protein kinase C following peripheral nerve injury Mao, J.;Price, D. D.;Mayer, D. J.;Hayes, R. L.
  14. Neurosci. Lett. v.198 Increases in protein kinase C gamma immunoreactivity in the spinal cord dorsal horn of rats with painful mononeuropathy Mao, J.;Price, D. D.;Phillips, L. L.;David, J. L.;Mayer, J.
  15. Neuroscience v.71 no.2 Acute thermal hyperalgesia in the rat produced by activation of N-methyl-D-aspartate receptors and protein kinase C and production of nitric oxide Meller, S. T.;Dykstra, C.;Gebhart, C. F.
  16. J. Neurosci. v.8 Distribution of protein kinase C-like immunoreactive neurons in rat brain Saito, N.;Kikkawa, U.;Nishizuka, Y.;Tanaka, C. H.
  17. J. Neurophysiol. v.71 no.2 The effect of phorbol esters on the responses of Primate spinothalamic neurons to mechanical and thermal stimuli Palecek, J.;Paleckova, V.;Dougherty, P. M.;Willis, W. D.
  18. J. Neurosci. v.12 no.9 The contribution of excitatory amino acids to central sensitization and persistent nociception after formalin-induced tissue injury Coderre, T. J.;Melzack, R.
  19. Eur. J. Neurosci. v.6 Intracellular messengers contributing persistent nociception and hyperalgesia induced by L-glutamate and substance P in the rat formalin pain model Coderre, T. J.;Yashpal, K.
  20. Neurosci. Lett. v.140 Contribution of protein kinase C to central sensitization and persistent pain following tissue injury Coderre, T. J.
  21. Trends. Neurosci. v.17 no.10 Modulation of spinal excitability amino acid neurotransmitters Urban, L.;Thompson, S. W. N.;Dray, A.
  22. J. Neurosci. v.14 no.4 Thermal hyperalgesia in association with the development of morphine tolerence in rats : roles of excitatory amino acid receptors and protein kinas C. Mao, J.;Price, D. D.;Mayer, D. J.
  23. J. Physiol. v.449 Protein kinase C-mediated enhancement of NMDA currents by metabotropic glutamate receptors in xenopus oocytes Kelso, S. R.;Nelson, T. E.;Leonard, J. P.
  24. Pain v.41 Excitatory amino acid receptors and nociceptive neurotransmission in rat spinal cord Aanonsen, L. M.;Lei, S.;Wilcox, G. L.
  25. FASEB J. v.6 Phosphorylation of ligandgated ion channels : a possible mode of synaptic plasticity Swope, S. L.;Moss, S. J.;Blackstone, C. D.;Huganir, R. L.
  26. Nature v.356 Protein kinase C reduces $Mg^{2+}$ block of NMDA-receptor channels as a mechanism of modulation Chen, L.;Huang, L. Y.
  27. Eur.J. Neurosci. v.6 Is protein kinase C activity requires for the N-methyl-D-aspartate-evoked rise in cytosolic $Ca^{2+}$ in mouse striatal neurons? Murphy, N. P.;Cordier, J.;Glowinski, J.;Premont, J.
  28. Trends. Neurosci. v.15 Protein kinase C modulation of NMDA currents : an important link for LTP induction Ben-Ari, Y.;Aniksztejn, L.;Bregestovski, P.
  29. Eur. J. Neurosci. v.4 Nitric-oxide synthase activity selectively stimulated by NMDA receptors depends on protein kinase C activation in mouse striatal neurons Bockaert, J. A.
  30. Mol. Pharmacol. v.41 Activation of protein kinase C selectively inhibits the gamma-aminobutyric acid receptor-role of desensitization Leidenheimer, N. J.;Mcquilkin, S. J.;Hahner, L. D.;Whiting, P.;Harris, R. A.
  31. J. Neurochem. v.67 Activation of protein kinase C augments peptide release from rat sensory neurons Barber, L. A.;Vasko, M. R.
  32. J. Pharmacol. Toxicol. Methods. v.32 no.4 A method to perform direct transcutaneous intrathecal injection in rats Mestre, C.;Pelissier, T.;Fialip, J.;Wilcox, G.;Eschalier, A.
  33. Physiol. Behav. v.17 Chronic catheterization of the spinal subarachnoid space Yaksh, T. L.;Rudy, T. A.
  34. Physiol. Behav. v.27 An improved method for chronic catheterization of the rat spinal subarachnoid space LoPachin, R. M.;Rudy, T. A.
  35. Anesthesiology v.77 Comparison of the antinociceptive effects of pre and posttreatment with intrathecal morphine and MK-801, an NMDA antagonist, on the formalin test in the rat Yamamoto, T.;Tony, M. D.;Yaksh, L.
  36. Pain v.59 The utility of excitatory amino acid(EAA) antagonists as analgesic agents. Ⅰ. Comparison of the nociceptive activity of various classes of EAA antagonists in mechanical, thermal and chemical nociceptive tests Coderre, T. J.;Empel, I. V.
  37. Brain Res. Rev. v.16 Excitatory amino acid receptor, neural membrane phospholipid metabolism and neurological disorders Farooqui, A. A.;Horrocks, L. A.
  38. Prog. Neurobiol. v.28 The physiology of excitatory amino acid in vetebrate central nervous system Mayer, M. L.;Westbrook, G. L.
  39. J. Physiol. v.496 no.2 Protein kinase C-mediated enhancement of glycine response in rat sacral dorsal commissural neurones by serotonin Tian-Le Xu, T. L.;Nabekura, J.;Akaike, N.