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• W2080761218 abstract "Tachykinins produce concentration-dependent contraction of the human isolated bronchus by stimulation of receptors that belong to the NK2 type. The aim of this study was to investigate the inhibitory effects of a new, potent, and selective nonpeptide antagonist of the neurokinin A (NKA) (NK2) receptors, SR 48968 [(S)-N-methyl-N-[4-acetylamino-4-phenylpiperidino-2-(3,4-dichlorophenyl) butyl]benzamide] on human isolated airways. Our experiments were performed on human isolated bronchi obtained from patients with lung cancer. Phosphoramldon, 10−5 M, was added to the bath to inhibit neurokinin metabolism. SR 48968 induced a parallel shift to the right of the concentration-response (C/R) curves to [Nie10]-NKA(4-10), a specific NK2 receptor agonist. The antagonism was of the competitive type, with a pA2 of 9.40 ± 0.19 (slope = 0.95 ± 0.08, n = 13). The (R)-enantiomer of SR 48968 was 100-fold less potent and a noncompetitive antagonist (slope = 0.56 ± 0.11, n = 8); pA2 and slope of the racemate were 8.86 ± 0.21 and 1.09 ± 0.21 (n = 7), respectively. Under similar conditions, racemic CP-96,345, a nonpeptide NK1 antagonist, did not modify the C/R curves to [Nie10]-NKA(4-10) until 10−7 M. SR 48968 did not modify C/R curves to acetylcholine, histamine, KCl, or PGF2α on the human isolated bronchus. Finally, SR 48968 shifted to the right C/R curves to substance P on isolated human bronchi, whereas racemic CP-96,345 was without effect. In conclusion, SR 48968 appears to be a potent antagonist of neurokinin NK2 receptors on the human isolated bronchus and may be an interesting tool for studying the physiologic and Physiopathologic role of NKA. Furthermore, SP-induced contraction of the isolated human bronchus (10−8 to 10−5 M) involves only NK2 receptor stimulation." @default.
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• W2080761218 date "1992-11-01" @default.
• W2080761218 modified "2023-09-25" @default.
• W2080761218 title "Effects on the Isolated Human Bronchus of SR 48968, a Potent and Selective Nonpeptide Antagonist of the Neurokinin A (NK₂) Receptors" @default.
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• W2080761218 doi "https://doi.org/10.1164/ajrccm/146.5_pt_1.1177" @default.
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