TACHYKININ RECEPTORS IN GUINEA-PIG AIRWAYS - CHARACTERIZATION USING SELECTIVE LIGANDS

Tachykinin receptors in guinea-pig airways were examined using radioli gand binding techniques in lung homogenates, and using isolated bronch ial segments. Binding of the NK1 selective radioligand I-125-labelled Bolton-Hunter [Sar(9),Met(O-2)(11)]substance P ([I-125]BHSarSP) was sa turable and of high affinity (K-D, 0.26 nM). The rank potency order of competitors for ([I-125]BHSarSP binding was [Pro(9)]SP > CP 96345 muc h greater than septide > [pGlu(6)]SP(6-11) > RP 67580 greater than or equal to [DPro(9)t beta Pro(10)(phi),Trp(11)]SP > [DPro(9),t beta Pro( 10)(CH2 phi),Trp(11)]physalaemin greater than or equal to GR 82334 gre ater than or equal to I-127 Bolton-Hunter neurokinin A (BHNKA). Septid e had higher affinity than expected, and it was the only ligand to bin d to two sites. Agonists interacting with NK2 receptors were more pote nt contractile agents than NK1 receptor agonists. Responses to BHNKA ( pD(2) 8.4) were antagonized by MDL 29913 and MEN 10207, with pK(B) val ues 6.42 and 6.79, and also by SR 48968 and GR 94800, although this wa s not dose dependent. This agonist was also weakly inhibited by CP 963 45 and RP 67580. These data demonstrate that BHNKA can interact with b oth NK1 and NK2 receptors. There was no relationship between the bindi ng affinity of NK1 ligands in lung homogenates, with GR 82334 being no tably weak, and their agonist or antagonist potency in bronchial smoot h muscle.