神经激肽B和特异性速激肽NK(3)受体激动剂诱导豚鼠气道高反应性。

Neurokinin B- and specific tachykinin NK(3) receptor agonists-induced airway hyperresponsiveness in the guinea-pig.

作者信息

Daoui S, Naline E, Lagente V, Emonds-Alt X, Advenier C

机构信息

Laboratoire de Pharmacologie, Faculté de Médecine Paris-Ouest, 15 Rue de l'Ecole de Médecine, F75006 Paris, France.

出版信息

Br J Pharmacol. 2000 May;130(1):49-56. doi: 10.1038/sj.bjp.0703278.

DOI:10.1038/sj.bjp.0703278

PMID:10780997

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1572035/

Abstract

The aim of this study was to determine whether neurokinin B (NKB) or specific agonists of tachykinin NK(3) receptors, [MePhe(7)]NKB and senktide, were able to induce airway hyperresponsiveness in guinea-pigs. The effects of these compounds were compared to those of substance P (SP), neurokinin A (NKA) and the preferential tachykinin NK(1) ([Sar(9), Met(0(2))(11)]SP) or NK(2) ([betaAla(8)]NKA (4-10)) receptor agonists. 2. In guinea-pigs pretreated with phosphoramidon (10(-4) M aerosol for 10 min) and salbutamol (8.7x10(-3) M for 10 min), all tachykinins administrated by aerosol (3x10(-7) to 10(-4) M) induced airway hyperresponsiveness 24 h later, displayed by an exaggerated response to the bronchoconstrictor effect of acetylcholine (i.v.). The rank order of potency was: [betaAla(8)]NKA (4-10)>NKA=NKB=senktide=[MePhe(7)]NKB=[Sar(9),Met(0(2))(11)]SP>SP. 3. Airway hyperresponsiveness induced by [MePhe(7)]NKB was prevented by the tachykinin NK(3) (SR 142801) and NK(2) (SR 48968) receptor antagonists. 4. Bronchoconstriction induced by tachykinins administered by aerosol was also determined. SP, NKA, NKB and the tachykinin NK(1) and NK(2) receptor agonist induced bronchoconstriction. The rank order of potency was: NKA=[betaAla(8)]NKA (4-10)>NKB=SP=[Sar(9), Met(0(2))(11)]SP. Under similar conditions, and for concentrations which induce airway hyperresponsiveness, senktide and [MePhe(7)]NKB failed to induce bronchoconstriction. 5. It is concluded that tachykinin NK(3)-receptor stimulation can induce airway hyperresponsiveness and that this effect is not related to the ability of tachykinins to induce bronchoconstriction.

摘要

本研究的目的是确定神经激肽B（NKB）或速激肽NK(3)受体的特异性激动剂[MePhe(7)]NKB和森克肽是否能够在豚鼠中诱导气道高反应性。将这些化合物的作用与P物质（SP）、神经激肽A（NKA）以及速激肽NK(1)（[Sar(9), Met(0(2))(11)]SP）或NK(2)（[βAla(8)]NKA (4 - 10)）受体激动剂的作用进行比较。2. 在预先用磷酰胺（10(-4) M气雾剂处理10分钟）和沙丁胺醇（8.7x10(-3) M处理10分钟）处理的豚鼠中，所有通过气雾剂给予的速激肽（3x10(-7)至10(-4) M）在24小时后均诱导气道高反应性，表现为对乙酰胆碱（静脉注射）支气管收缩作用的过度反应。效力的顺序为：[βAla(8)]NKA (4 - 10)>NKA=NKB=森克肽=[MePhe(7)]NKB=[Sar(9),Met(0(2))(11)]SP>SP。3. [MePhe(7)]NKB诱导的气道高反应性可被速激肽NK(3)（SR 142801）和NK(2)（SR 48968）受体拮抗剂阻断。4. 还测定了通过气雾剂给予速激肽所诱导的支气管收缩。SP、NKA、NKB以及速激肽NK(1)和NK(2)受体激动剂均诱导支气管收缩。效力顺序为：NKA=[βAla(8)]NKA (4 - 10)>NKB=SP=[Sar(9), Met(0(2))(11)]SP。在相似条件下，对于诱导气道高反应性的浓度，森克肽和[MePhe(7)]NKB未能诱导支气管收缩。5. 得出的结论是，速激肽NK(3)受体刺激可诱导气道高反应性，且这种效应与速激肽诱导支气管收缩的能力无关。