HETEROGENEITY OF TACHYKININ RECEPTORS IN THE RABBIT LUNG

The tachykinins, substance P (SP) and neurokinin A (NKA), are agonists for the NK1 and NK2 receptors, respectively. Tachykinins have various respiratory effects, including bronchoconstriction. This study charac terizes tachykinin binding sites in the rabbit lung. We hypothesize th at (2-[I-125]iodohistidyl(1))Neurokinin A ([I-125]NKA) interacts with NK1 and NK2 binding sites in the rabbit lung. The K-d determined from saturation isotherms was 0.69 x/divided by 1.14 nM (geometric mean x/d ivided by SEM) and the B-max was 4.15 +/- 0.22 femtomole/mg protein (a rithmetic mean +/- SEM). Competitive inhibition studies with NKA, SP a nd various selective tachykinin agonists showed the rank order of pote ncy: [beta-Ala(8)]-Neurokinin A 4-10 = SP much greater than NKA much g reater than [Sar(9),Met(O-2)(11)]-Substance P. [beta-Ala(8)]-Neurokini n A 4-10, a selective NK2 agonist, and SP inhibition of [I-125]NKA bin ding were best described using a two-site model. Competitive inhibitio n studies using the selective nonpeptide NK2 antagonist (SR 48968) and the selective nonpeptide NK1 antagonist (CP 96,345) revealed K-i's of 5.5 nM and 8.1 nM, respectively. Our data therefore suggest that [I-1 25]NKA binds to both the NK1 and NK2 receptors in the lung.