Andoh T, Nagasawa T, Satoh M, Kuraishi Y
Department of Applied Pharmacology, Faculty of Pharmaceutical Sciences, Research Institute for Wakan-yaku, Toyama Medical & Pharmaceutical University, Toyama, Japan.
J Pharmacol Exp Ther. 1998 Sep;286(3):1140-5.
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 microgram site-1) into the rostral back of the ICR mouse dose-dependently produced scratching of the injected site. The SP- (135 microgram 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 (WBB6F1 W/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 NK1 receptor 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.
我们开展实验以确定P物质（SP）是否会引发小鼠体内由肥大细胞介导的瘙痒感。向ICR小鼠的鼻背部皮内注射SP（10 - 135微克/部位）会使注射部位产生剂量依赖性的抓挠。SP（135微克/部位 = 100纳摩尔/部位）诱导的抓挠会被辣椒素（重复给药）和纳洛酮抑制；这些特征与人类的瘙痒相似。SP在肥大细胞缺陷型（WBB6F1 W/Wv）小鼠以及对照（+/+）小鼠中均能引发抓挠。用化合物48/80预处理在肥大细胞缺陷型小鼠以及对照+/+和ICR小鼠中对SP诱导的抓挠产生相似程度的抑制。皮内注射NK1受体激动剂GR73632会产生剂量依赖性的抓挠，而NK2激动剂GR64349和NK3激动剂senktide则无此作用。SP诱导的抓挠会被NK1受体拮抗剂spantide和L - 668,169抑制，但不会被NK2拮抗剂L - 659,877抑制。结果表明，皮内注射SP诱导的小鼠抓挠是一种与瘙痒相关的反应。SP的作用可能至少部分由皮肤NK1受体介导，并且肥大细胞可能不是SP诱导瘙痒的关键因素。
