Autoradiographic localization of tachykinin NK2 and NK1 receptors in the guinea-pig lung, using selective radioligands.

The distribution of tachykinin receptors in guinea-pig airways was studied using newly developed selective radioligands, [125I][Lys5,Tyr(I2)7,MeLeu9,Nle10]neurokinin A-(4-10) for NK2 receptors and [125I]Bolton-Hunter-[Sar9,Met(O2)11]substance P for NK1 receptors. Optimum incubation times were 60 and 45 min for tachykinin NK2 and NK1 sites, respectively, in slide-mounted sections of guinea-pig lung. Bacitracin (40 micrograms/ml) greatly reduced specific binding of [125I][Lys5,Tyr(I2)7,MeLeu9,Nle10]neurokinin A-(4-10), whereas phosphoramidon (1 and 10 microM) and bacitracin (40 micrograms/ml) significantly increased the specific binding of [125I]Bolton-Hunter-[Sar9,Met(O2)11]substance P. Dense specific binding of [125I]Bolton-Hunter-[Sar9,Met(O2)11]substance P occurred over bronchial smooth muscle of large and small airways, with moderate binding on bronchial epithelium and over pulmonary arterial smooth muscle. Moderate specific binding of [125I][Lys5,Tyr(I2)7, MeLeu9,Nle10]neurokinin A-(4-10) was associated with bronchial smooth muscle of mainly large airways but not with other histological regions. This is the first autoradiographic report of (a low density of) tachykinin NK2 binding sites on airway smooth muscle and supports the potent actions of NK2 receptor ligands as contractile agents in guinea-pig isolated bronchi.