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Glucosylsphingosine Induces Itch-Scratch Responses in Mice

  • Received : 2010.07.05
  • Accepted : 2010.07.15
  • Published : 2010.07.31

Abstract

Pruritus is one of major symptoms in atopic dermatis. The pathophysiological mechanism of pruritus is unclear. The search for pruritogen is important in elucidating the pathophysiological mechanism of pruritus in atopic dermatitis. Glucosylsphingosine (Gsp) is upregulated in the strateum corneum of atopic dermatitis patients. We investigated to determine whether Gsp induces itch-scratch responses (ISRs) in mice. Intradermal administration of Gsp induces ISRs. Gsp dose-dependently induced scratching response at 50-500 nmol/site range. Pretreatment with naltrexone, an opioid $\mu$ receptor antagonist, and capsaicin, a TrpV1 receptor agonist, inhibited Gsp-induced ISRs. Additionally, Gsp-induced ISRs were also suppressed by cyproheptadine, an antagonist of serotonin receptor. These findings suggest that Gsp-induced scratching might be at least partly mediated by capsaicin-sensitive primary afferents, and the opioids receptor systems might be involved in transmission of itch signaling in the central nervous system. Furthermore, our findings suggest that Gsp-induced ISRs may be attributable to the serotonin-mediated pathways and Gsp is not any more one of byproducts of abnormal skin barrier but can lead to induce pruritus, one of typical symptoms of atopic dermatitis.

Keywords

References

  1. Bevan, S. and Szolcsanyi, J. (1990). Sensory neuron-specific actions of capsaicin: mechanisms and applications. Trends Pharmacol. Sci. 11, 330-333.
  2. Bielory, L., Goodman, P. E. and Fisher, E. M. (2001). Allergic ocular disease. A review of pathophysiology and clinical presentations. Clin. Rev. Allergy Immunol. 20, 183-200. https://doi.org/10.1385/CRIAI:20:2:183
  3. Bienkowski, P., Kostowski, W. and Koros, E. (1999). Ethanolreinforced behaviour in the rat: effects of naltrexone. Eur. J. Pharmacol. 374, 321-327. https://doi.org/10.1016/S0014-2999(99)00245-9
  4. Choi, H., Kim, S., Kim, H. J., Kim, K. M., Lee, C. H., Shin, J. H.and Noh, M. (2010). Sphingosylphosphorylcholine downregulates filaggrin gene transcription through NOX5- based NADPH oxidase and cyclooxygenase-2 in human keratinocytes. Biochem. Pharmacol. 80, 95-103. https://doi.org/10.1016/j.bcp.2010.03.009
  5. Cook, P. R. (1996). Seasonal allergic rhinitis. Mo. Med. 93,247-250.
  6. Fu, L. W., Pan, H. L. and Longhurst, J. C. (1997). Endogenous histamine stimulates ischemically sensitive abdominal visceral afferents through H1 receptors. Am. J. Physiol. 273, H2726-2737.
  7. Han, M., Kim, Y. L., Sacket, S. J., Kim, K., Kim, H. L., Jo, J. Y.,Ha, N. C. and Im, D. S. (2007). Effect of direct albumin binding to sphingosylphosphorylcholine in Jurkat T cells.Prostaglandins Other Lipid Mediat. 84, 174-183. https://doi.org/10.1016/j.prostaglandins.2007.08.003
  8. Han, S. K., Mancino, V. and Simon, M. I. (2006). Phospholipase Cbeta 3 mediates the scratching response activated by the histamine H1 receptor on C-fiber nociceptive neurons.Neuron 52, 691-703. https://doi.org/10.1016/j.neuron.2006.09.036
  9. Hashimoto, T., Ohata, H. and Momose, K. (2004). Itch-scratch responses induced by lysophosphatidic acid in mice. Pharmacology 72, 51-56. https://doi.org/10.1159/000078632
  10. Holzer, P. (1988). Local effector functions of capsaicin-sensitive sensory nerve endings: involvement of tachykinins, calcitonin gene-related peptide and other neuropeptides. Neuroscience 24, 739-768. https://doi.org/10.1016/0306-4522(88)90064-4
  11. Imokawa, G. (2009). A possible mechanism underlying the ceramide deficiency in atopic dermatitis: expression of a deacylase enzyme that cleaves the N-acyl linkage of sphingomyelin and glucosylceramide. J. Dermatol. Sci. 55, 1-9. https://doi.org/10.1016/j.jdermsci.2009.04.006
  12. Inagaki, N., Nakamura, N., Nagao, M., Kawasaki, H. and Nagai,H. (2000). Inhibition of passive cutaneous anaphylaxisassociated scratching behavior by mu-opioid receptor antagonists in ICR mice. Int. Arch. Allergy Immunol. 123, 365-368. https://doi.org/10.1159/000053650
  13. Kim, D. K., Kim, H. J., Kim, H., Koh, J. Y., Kim, K. M., Noh, M.S., Kim, J. J. and Lee, C. H. (2008a). Involvement of serotonin receptors 5-HT1 and 5-HT2 in 12(S)-HPETE-induced scratching in mice. Eur. J. Pharmacol. 579, 390-394. https://doi.org/10.1016/j.ejphar.2007.11.005
  14. Kim, H. J., Kim, D. K., Kim, H., Koh, J. Y., Kim, K. M., Noh, M.S., Lee, S., Kim, S., Park, S. H., Kim, J. J., Kim, S. Y. andLee, C. H. (2008b). Involvement of the BLT2 receptor in the itch-associated scratching induced by 12-(S)-lipoxygenase products in ICR mice. Br. J. Pharmacol. 154, 1073-1078. https://doi.org/10.1038/bjp.2008.220
  15. Kim, H. J., Kim, H., Han, E. S., Park, S. M., Koh, J. Y., Kim, K.M., Noh, M. S., Kim, J. J. and Lee, C. H. (2008c). Characterizations of sphingosylphosphorylcholine-induced scratching responses in ICR mice using naltrexon, capsaicin, ketotifen and Y-27632. Eur. J. Pharmacol. 583, 92-96. https://doi.org/10.1016/j.ejphar.2008.01.005
  16. Leung, D. Y. and Bieber, T. (2003). Atopic dermatitis. Lancet361, 151-160. https://doi.org/10.1016/S0140-6736(03)12193-9
  17. Lloyd-Evans, E., Pelled, D., Riebeling, C., Bodennec, J., de-Morgan, A., Waller, H., Schiffmann, R. and Futerman, A. H.(2003). Glucosylceramide and glucosylsphingosine modulate calcium mobilization from brain microsomes via different mechanisms. J. Biol. Chem. 278, 23594-23599. https://doi.org/10.1074/jbc.M300212200
  18. Lorette, G. and Vaillant, L. (1990). Pruritus. Current concepts in pathogenesis and treatment. Drugs 39, 218-223. https://doi.org/10.2165/00003495-199039020-00005
  19. Meyer zu Heringdorf, D. and Jakobs, K. H. (2007). Lysophospholipid receptors: signalling, pharmacology and regulation by lysophospholipid metabolism. Biochim. Biophys. Acta.1768, 923-940. https://doi.org/10.1016/j.bbamem.2006.09.026
  20. Nilsson, O. and Svennerholm, L. (1982). Accumulation of glucosylceramide and glucosylsphingosine (psychosine) in cerebrum and cerebellum in infantile and juvenile Gaucher disease. J. Neurochem. 39, 709-718. https://doi.org/10.1111/j.1471-4159.1982.tb07950.x
  21. Okamoto, R., Arikawa, J., Ishibashi, M., Kawashima, M.,Takagi, Y. and Imokawa, G. (2003). Sphingosylphosphorylcholine is upregulated in the stratum corneum of patients with atopic dermatitis. J. Lipid Res. 44, 93-102. https://doi.org/10.1194/jlr.M200225-JLR200
  22. Orvisky, E., Park, J. K., LaMarca, M. E., Ginns, E. I., Martin, B.M., Tayebi, N. and Sidransky, E. (2002). Glucosylsphingosine accumulation in tissues from patients with Gaucher disease: correlation with phenotype and genotype. Mol. Genet. Metab. 76, 262-270. https://doi.org/10.1016/S1096-7192(02)00117-8
  23. Palmer, C. N., Irvine, A. D., Terron-Kwiatkowski, A., Zhao, Y.,Liao, H., Lee, S. P., Goudie, D. R., Sandilands, A., Campbell,L. E., Smith, F. J., O'Regan, G. M., Watson, R. M., Cecil, J.E., Bale, S. J., Compton, J. G., DiGiovanna, J. J., Fleckman,P., Lewis-Jones, S., Arseculeratne, G., Sergeant, A., Munro,C. S., El Houate, B., McElreavey, K., Halkjaer, L. B.,Bisgaard, H., Mukhopadhyay, S. and McLean, W. H. (2006).Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat. Genet. 38, 441-446. https://doi.org/10.1038/ng1767
  24. Purcell, W. M., Cohen, D. L. and Hanahoe, T. H. (1989).Comparison of histamine and 5-hydroxytryptamine content and secretion in rat mast cells isolated from different anatomical locations. Int. Arch. Allergy Appl. Immunol. 90,382-386. https://doi.org/10.1159/000235058
  25. Stander, S. and Steinhoff, M. (2002). Pathophysiology of pruritus in atopic dermatitis: an overview. Exp. Dermatol. 11, 12-24. https://doi.org/10.1034/j.1600-0625.2002.110102.x
  26. Suh, H. W., Chung, K. M., Kim, Y. H., Huh, S. O. and Song, D.K. (1999). Effects of histamine receptor antagonists injected intrathecally on antinociception induced by opioids administered intracerebroventricularly in the mouse. Neuropeptides 33, 121-129. https://doi.org/10.1054/npep.1999.0006
  27. Yosipovitch, G., Greaves, M. W. and Schmelz, M. (2003). Itch. Lancet 361, 690-694. https://doi.org/10.1016/S0140-6736(03)12570-6

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