Lack of evidence for tachykinin NK1 receptor-mediated neutrophil accumulation in the rat cutaneous microvasculature by thermal injury

The effect of the non-peptide selective tachykinin NK1 receptor antagonist SR140333 has been investigated on oedema formation and neutrophil accumulat ion induced by thermal injury (50 degrees C for 5 min), mustard oil, substa nce P, the tachykinin NK1 agonist GR73632, and interleukin-1 beta in the ab dominal skin of the anaesthetised rat. SR140333 significantly inhibited (12 0 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 bloc ked NK1 receptors for 5 h (SR140333, 240 nmol/kg i.v. + 240 nmol/kg s.c.) f ailed to influence neutrophil accumulation measured 5 h after thermal-injur y. Thus, the neurogenic component mediated by NK1 receptors is important to elicit the early oedema formation, but does not influence subsequent neutr ophil accumulation. Topical application of mustard oil (2%), a neurogenic i nflammation 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 elic it neutrophil accumulation. Neutrophil accumulation induced by interleukin- 1 beta (0.03-3 pmol i.d.) was not affected by SR140333 pretreatment. In con clusion, despite an early pronounced tachykinin NK1 receptor-dependent oede ma response after thermal injury, the results suggest that subsequent neutr ophil accumulation is not mediated by NK1 receptors. Furthermore, we have n ot obtained any evidence to suggest that either endogenous or exogenous tac hykinins can directly induce neutrophil accumulation in the rat cutaneous m icrovasculature. (C) 1999 Elsevier Science B.V. All rights reserved.