Coulson F R, Bigg C S, O'Donnell S R
Department of Physiology and Pharmacology, School of Biomedical Sciences, The University of Queensland, Brisbane, Australia.
Inflamm Res. 2002 Jul;51(7):317-23. doi: 10.1007/pl00000310.
To examine whether NKP608, a novel 1-benzoyl-2-benzyl-4-aminopiperidine NK1 receptor antagonist, inhibits substance P (SP)-induced airway plasma protein exudation in vivo.
Anaesthetised English shorthair guinea-pigs and Wistar rats.
Tachykinin peptides were applied topically onto the trachea and antagonists administered intravenously.
Tracheal segments isolated in situ were perfused with saline and plasma-derived protein assayed in the perfusate.
SP (1 microM) caused plasma protein exudation, which was abolished by an NK1 antagonist (RP 67580,1.75 micromol/kg) but unaffected by an NK2 antagonist (SR 48968, 1.75 micromol/ kg) indicating the response is NK1-receptor-mediated. This was confirmed with a response to an NK1 agonist ([Sar9, Met(O2)11]-SP, 1 microM) but none to an NK2 agonist ([betaAla8]-neurokinin A(4-10), 1 microM). NKP608 inhibited SP responses with estimated ID50 values (micromol/kg) of 0.0044 (guinea-pigs) and 0.19 (rats).
NKP608 is an antagonist in vivo of NK1 receptor-induced tracheal plasma protein exudation and is more potent in guinea-pigs than rats.
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