Neurokinin B- and specific tachykinin NK3 receptor agonists-induced airwayhyperresponsiveness in the guinea-pig

1 The aim of this study was to determine whether neurokinin B (NKB) or spec ific agonists of tachykinin NK3 receptors, [MePhe(7)]NKB and senktide, were able to induce airway hyperresponsiveness in guinea-pigs. The effects of t hese compounds were compared to those of substance P (SP), neurokinin A (NK A) and the preferential tachykinin NK1 ([Sar(9), Met(0(2))(11)]SP) or NK2 ( [beta Ala(8)]NKA (4-10)) receptor agonists. 2 In guinea-pigs pretreated with phosphoramidon (10(-4) M aerosol for 10 mi n) and salbutamol (8.7 x 10(-3) M for 10 min), all tachykinins administrate d by aerosol (3 x 10(-7) to 10(-4) M) induced airway hyperresponsiveness 24 h later, displayed by an exaggerated response to the bronchoconstrictor ef fect of acetylcholine (i.v.). The rank order of potency was: [beta Ala(8)]N KA (4-10) > NKA = NKB = senktide = [MePhe(7)]NKB = [Sar(9),Met(0(2))(11)]SP > SP. 3 Airway hyperresponsiveness induced by [MePhe(7)]NKB was prevented by the tachykinin NK3 (SR 142801) and NK2 (SR 48968) receptor antagonists. 4 Bronchoconstriction induced by tachykinins administered by aerosol was al so determined. SP, NKA, NKB and the tachykinin NK1 and NK2 receptor agonist induced bronchoconstriction. The rank order of potency was: NKA = [beta Al a(8)]NKA (4-10) > NKB = SP = [Sar(9),Met(0(2))(11)]SP. Under similar condit ions, and for concentrations which induce airway hyperresponsiveness, senkt ide and [MePhe(7)]NKB failed to induce bronchoconstriction. 5 It is concluded that tachykinin NK3-receptor stimulation can induce airwa y hyperresponsiveness and that this effect is not related to the ability of tachykinins to induce bronchoconstriction.