Bronchoconstrictor effect of the tachykinin NK₃-receptor agonists [MePhe⁷]-neurokinin B and senktide in the isolated guinea pig lung

Abstract

To determine whether bronchoconstriction can be mediated via the tachykinin NK₃ receptors, isolated guinea pig lungs were challenged with the exogenous tachykinin NK₃-receptor agonists [MePhe⁷]-neurokinin B ([MePhe⁷]-NKB) and senktide. [MePhe⁷]-NKB induced bronchoconstriction (EC50 = 11.8 ± 1.7 µM) that was significantly inhibited by the tachykinin NK₃-receptor antagonist SB 223412 at 10 µM (EC50 = 24.4 ± 4.5 µM). Senktide also induced bronchoconstriction (EC50 = 96.2 ± 20.3 µM) and the bronchoconstriction was significantly reduced by SB 223412 at 1 and 10 µM (EC50 = 270.8 ± 78.9 µM and 388.3 ± 105.5 µM, respectively). Although the authors demonstrated that SB 223412, [MePhe⁷]-NKB, and senktide are potent and selective for the tachykinin NK3 receptors in binding and functional (Ca(2+) mobilization) assays, the tachykinin NK₁-receptor antagonist CP 99,994 at 1 µM (EC50 = 32.7 ± 8.5 µM) produced inhibition of [MePhe⁷]-NKB-induced bronchoconstriction, whereas the tachykinin NK₂-receptor antagonist SR 48968 at 0.1 µM (EC50 = 213.2 ± 42.9 µM) blocked senktide-induced bronchoconstriction. These data suggest that [MePhe⁷]-NKB and senktide caused bronchoconstriction in guinea pig through activation of the tachykinin NK₃-receptors but the tachykinin NK₁- and/or NK₂-receptors are also involved in the response.

Ablation of KNDy Neurons Results in Hypogonadotropic Hypogonadism and Amplifies the Steroid-Induced LH Surge in Female Rats

“…[MePhe 7 ]-NKB was selected for conjugation to SAP because it is 1000 times more selective for NK 3 R than other tachykinin receptors (36,37). In addition, the binding of [MePhe 7 ]-NKB to SAP did not change its affinity for the NK 3 R (31).…”

Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes

“…[MePhe 7 ]NKB, like senktide, has greater affinity for NK 3 R than NKB, and is 1000 times more selective for NK 3 R than other tachykinin receptors (Corboz et al, 2010; Drapeau et al, 1987). Stereotaxic injections of NK 3 -SAP destroyed nearly all the kisspeptin and NKB-immunoreactive neurons in the arcuate nucleus (Mittelman-Smith et al, 2012b).…”