Tachykinin receptors in guinea-pig airways: characterization using selective ligands.

Abstract:

:Tachykinin receptors in guinea-pig airways were examined using radioligand binding techniques in lung homogenates, and using isolated bronchial segments. Binding of the NK1 selective radioligand 125I-labelled Bolton-Hunter [Sar9,Met(O2)11]substance P ([125I]BHSarSP) was saturable and of high affinity (KD, 0.26 nM). The rank potency order of competitors for [125I]BHSarSP binding was [Pro9]SP > CP 96345 > septide > [pGlu6]SP(6-11) > RP 67580 > or = [DPro9,t beta Pro10(phi),Trp11]SP > [DPro9,t beta Pro10(CH2 phi),Trp11]physalaemin > or = GR82334 > or = 127I Bolton-Hunter neurokinin A (BHNKA). Septide had higher affinity than expected, and it was the only ligand to bind to two sites. Agonists interacting with NK2 receptors were more potent contractile agents than NK1 receptor agonists. Responses to BHNKA (pD2 8.4) were antagonized by MDL 29913 and MEN 10207, with pKB values 6.42 and 6.79, and also by SR 48968 and GR 94800, although this was not dose dependent. This agonist was also weakly inhibited by CP 96345 and RP 67580. These data demonstrate that BHNKA can interact with both NK1 and NK2 receptors. There was no relationship between the binding affinity of NK1 ligands in lung homogenates, with GR 82334 being notably weak, and their agonist or antagonist potency in bronchial smooth muscle.

authors

Burcher E,Zeng XP,Strigas J,Geraghty DP,Lavielle S

doi

10.1139/y95-126

subject

Has Abstract

pub_date

1995-07-01 00:00:00

pages

915-22

issue

7

eissn

0008-4212

issn

1205-7541

journal_volume

73

pub_type

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