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
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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.
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↵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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