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 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.
Pintér
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E
Cardiovascular Research Centre, Biomedical Sciences Division, King's College, London, UK.
Brown
B
B
Hoult
J R
JR
Brain
S D
SD
D000005:Abdomen / Q000294:innervation; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002056:Burns / Q000150:complications / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D006614:Hindlimb / Q000294:innervation; D006632:Histamine / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy; D007375:Interleukin-1 / Q000494:pharmacology; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009149:Mustard Plant; D064729:Neurokinin-1 Receptor Antagonists; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology; D010938:Plant Oils; D011812:Quinuclidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000819:agonists / Q000502:physiology*; D012867:Skin / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors
D007375:Interleukin-1; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments; D010880:Piperidines; D010936:Plant Extracts; D010938:Plant Oils; D011812:Quinuclidines; D018040:Receptors, Neurokinin-1; C068032:GR 73632; C085215:SR 140333; D013373:Substance P; D006632:Histamine; D001920:Bradykinin; C027793:mustard oil