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Research ArticleArticle

Substance P Induction of Itch-Associated Response Mediated by Cutaneous NK1 Tachykinin Receptors in Mice

Tsugunobu Andoh, Tetsuro Nagasawa, Masamichi Satoh and Yasushi Kuraishi
Journal of Pharmacology and Experimental Therapeutics September 1998, 286 (3) 1140-1145;
Tsugunobu Andoh
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Tetsuro Nagasawa
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Masamichi Satoh
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Yasushi Kuraishi
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Abstract

Our experiments were conducted to determine whether substance P (SP) would elicit an itch sensation mediated by mast cells in mice. An intradermal injection of SP (10–135 μg site−1) into the rostral back of the ICR mouse dose-dependently produced scratching of the injected site. The SP- (135 μg site−1 = 100 nmol site−1) induced scratching was inhibited by capsaicin (repeated administration) and naloxone; features being similar to itch in humans. SP elicited scratching in mast cell-deficient (WBB6F1W/Wv) mice as well as control (+/+) mice. Pretreatment with compound 48/80 produced similar degrees of inhibition of SP-induced scratching in mast cell-deficient mice as well as control +/+ and ICR mice. Intradermal injections of the NK1receptor agonist GR73632 produced dose-dependent scratching, while the NK2 agonist GR64349 and the NK3 agonist senktide were without effects. SP-induced scratching was inhibited by the NK1 receptor antagonists spantide and L-668,169, but not by the NK2 antagonist L-659,877. The results suggest that scratching of the mouse induced by an i.d. injection of SP is itch-associated response. The SP action may be mediated at least partly by cutaneous NK1 receptors, and mast cells may not be key factors in SP-induced itching.

Footnotes

  • Send reprint requests to: Dr. Yasushi Kuraishi, Department of Applied Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical & Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.

  • ↵1 This work was supported in part by Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan and the Tamura Foundation for Promotion of Science and Technology.

  • Abbreviations:
    GR64349
    Lys-Asp-Ser-Phe-Val-Gly-R-γ-lactam-Leu-Met-NH2
    GR73632
    NH2-(CH2)4-CO-Phe-Phe-Pro-NMeLeu-Met-NH2
    L-659
    877, cyclo(Gln-Trp-Phe-Leu-Met)
    L-668
    169, cyclo(Gln-d-Trp(NMe) Phe(R)Gly [ANC-2]Leu-Met)2
    NK
    neurokinin
    RM-ANOVA
    repeated measures analysis of variance
    SP
    substance P
    • Received February 9, 1998.
    • Accepted April 13, 1998.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 286, Issue 3
1 Sep 1998
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Research ArticleArticle

Substance P Induction of Itch-Associated Response Mediated by Cutaneous NK1 Tachykinin Receptors in Mice

Tsugunobu Andoh, Tetsuro Nagasawa, Masamichi Satoh and Yasushi Kuraishi
Journal of Pharmacology and Experimental Therapeutics September 1, 1998, 286 (3) 1140-1145;

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Research ArticleArticle

Substance P Induction of Itch-Associated Response Mediated by Cutaneous NK1 Tachykinin Receptors in Mice

Tsugunobu Andoh, Tetsuro Nagasawa, Masamichi Satoh and Yasushi Kuraishi
Journal of Pharmacology and Experimental Therapeutics September 1, 1998, 286 (3) 1140-1145;
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