Pintér E, Brown B, Hoult J R, Brain S D
Cardiovascular Research Centre, Biomedical Sciences Division, King's College, London, UK.
Eur J Pharmacol. 1999 Mar 12;369(1):91-8. doi: 10.1016/s0014-2999(99)00054-0.
The effect of the non-peptide selective tachykinin NK1 receptor antagonist SR140333 has been investigated on oedema formation and neutrophil accumulation induced by thermal injury (50 degrees C for 5 min), mustard oil, substance P, the tachykinin NK1 agonist GR73632, and interleukin-1beta in the abdominal skin of the anaesthetised rat. SR140333 significantly inhibited (120 nmol/kg i.v.) or prevented (240 nmol/kg i.v.) the early oedema formation (0-10 min) induced by thermal injury. However, a dosing strategy which blocked NK1 receptors for 5 h (SR140333, 240 nmol/kg i.v. + 240 nmol/kg s.c.) failed to influence neutrophil accumulation measured 5 h after thermal injury. Thus, the neurogenic component mediated by NK1 receptors is important to elicit the early oedema formation, but does not influence subsequent neutrophil accumulation. Topical application of mustard oil (2%), a neurogenic inflammation stimulant, caused NK1 receptor-mediated early neurogenic plasma extravasation, but did not induce cutaneous neutrophil accumulation over 5 h. Substance P and GR73632 at high doses (1 nmol/site) also failed to elicit neutrophil accumulation. Neutrophil accumulation induced by interleukin-1beta (0.03-3 pmol i.d.) was not affected by SR140333 pretreatment. In conclusion, despite an early pronounced tachykinin NK1 receptor-dependent oedema response after thermal injury, the results suggest that subsequent neutrophil accumulation is not mediated by NK1 receptors. Furthermore, we have not obtained any evidence to suggest that either endogenous or exogenous tachykinins can directly induce neutrophil accumulation in the rat cutaneous microvasculature.
已研究了非肽类选择性速激肽NK1受体拮抗剂SR140333对麻醉大鼠腹部皮肤因热损伤（50℃，5分钟）、芥子油、P物质、速激肽NK1激动剂GR73632和白细胞介素-1β诱导的水肿形成和中性粒细胞聚集的影响。SR140333显著抑制（静脉注射120 nmol/kg）或预防（静脉注射240 nmol/kg）热损伤诱导的早期水肿形成（0 - 10分钟）。然而，一种能阻断NK1受体5小时的给药策略（SR140333，静脉注射240 nmol/kg + 皮下注射240 nmol/kg）未能影响热损伤5小时后测得的中性粒细胞聚集。因此，由NK1受体介导的神经源性成分对引发早期水肿形成很重要，但不影响随后的中性粒细胞聚集。局部应用神经源性炎症刺激剂芥子油（2%）可引起NK1受体介导的早期神经源性血浆外渗，但在5小时内未诱导皮肤中性粒细胞聚集。高剂量（1 nmol/部位）的P物质和GR73632也未能引发中性粒细胞聚集。SR140333预处理不影响白细胞介素-1β（0.03 - 3 pmol，皮内注射）诱导的中性粒细胞聚集。总之，尽管热损伤后早期有明显的速激肽NK1受体依赖性水肿反应，但结果表明随后的中性粒细胞聚集不是由NK1受体介导的。此外，我们没有获得任何证据表明内源性或外源性速激肽能直接诱导大鼠皮肤微血管中的中性粒细胞聚集。
