Abstract
The effect of the non-peptide selective tachykinin NK 1 receptor antagonist SR140333 has been investigated on oedema formation and neutrophil accumulation induced by thermal injury (50°C for 5 min), mustard oil, substance P, the tachykinin NK 1 agonist GR73632, and interleukin-1β 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 NK 1 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 NK 1 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 NK 1 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-1β (0.03–3 pmol i.d.) was not affected by SR140333 pretreatment. In conclusion, despite an early pronounced tachykinin NK 1 receptor-dependent oedema response after thermal injury, the results suggest that subsequent neutrophil accumulation is not mediated by NK 1 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.
Published Version
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