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

Erika Pintér, Brent Brown, J. Robin S Hoult, Susan D. Brain

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

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°C for 5 min), mustard oil, substance P, the tachykinin NK1 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 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-1β (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. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)91-98
Number of pages8
JournalEuropean Journal of Pharmacology
Volume369
Issue number1
DOIs
Publication statusPublished - Mar 12 1999

Fingerprint

Tachykinin Receptors
Microvessels
Neutrophils
Hot Temperature
Skin
Wounds and Injuries
Edema
Tachykinins
Substance P
Interleukin-1
Neurogenic Inflammation
SR 140333

Keywords

  • Interleukin-1β
  • Mustard oil
  • Neutrophil accumulation
  • Plasma extravasation
  • SR140333
  • Thermal injury

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Lack of evidence for tachykinin NK1 receptor-mediated neutrophil accumulation in the rat cutaneous microvasculature by thermal injury. / Pintér, Erika; Brown, Brent; Hoult, J. Robin S; Brain, Susan D.

In: European Journal of Pharmacology, Vol. 369, No. 1, 12.03.1999, p. 91-98.

Research output: Contribution to journalArticle

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abstract = "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°C for 5 min), mustard oil, substance P, the tachykinin NK1 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 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-1β (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. Copyright (C) 1999 Elsevier Science B.V.",
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