Neurokinin B- and specific tachykinin NK(3) receptor agonists-induced airway hyperresponsiveness in the guinea-pig.
1. The aim of this study was to determine whether neurokinin B (NKB) or specific agonists of tachykinin NK(3) receptors, [MePhe(7)]NKB and senktide, were able to induce airway hyperresponsiveness in guinea-pigs. The effects of these compounds were compared to those of substance P (SP), neurokinin A (NKA) and the preferential tachykinin NK(1) ([Sar(9), Met(0(2))(11)]SP) or NK(2) ([betaAla(8)]NKA (4-10)) receptor agonists. 2. In guinea-pigs pretreated with phosphoramidon (10(-4) M aerosol for 10 min) and salbutamol (8.7x10(-3) M for 10 min), all tachykinins administrated by aerosol (3x10(-7) to 10(-4) M) induced airway hyperresponsiveness 24 h later, displayed by an exaggerated response to the bronchoconstrictor effect of acetylcholine (i.v.). The rank order of potency was: [betaAla(8)]NKA (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 NK(3) (SR 142801) and NK(2) (SR 48968) receptor antagonists. 4. Bronchoconstriction induced by tachykinins administered by aerosol was also determined. SP, NKA, NKB and the tachykinin NK(1) and NK(2) receptor agonist induced bronchoconstriction. The rank order of potency was: NKA=[betaAla(8)]NKA (4-10)>NKB=SP=[Sar(9), Met(0(2))(11)]SP. Under similar conditions, and for concentrations which induce airway hyperresponsiveness, senktide and [MePhe(7)]NKB failed to induce bronchoconstriction. 5. It is concluded that tachykinin NK(3)-receptor stimulation can induce airway hyperresponsiveness and that this effect is not related to the ability of tachykinins to induce bronchoconstriction.
Daoui
S
S
Laboratoire de Pharmacologie, Faculté de Médecine Paris-Ouest, 15 Rue de l'Ecole de Médecine, F75006 Paris, France.
Naline
E
E
Lagente
V
V
Emonds-Alt
X
X
Advenier
C
C
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000502:physiology; D016085:Bronchoconstrictor Agents / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D008297:Male; D015287:Neurokinin B / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D018042:Receptors, Neurokinin-3 / Q000819:agonists* / Q000187:drug effects; D013373:Substance P / Q000031:analogs & derivatives* / Q000494:pharmacology; D015320:Tachykinins / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D016085:Bronchoconstrictor Agents; D010446:Peptide Fragments; D010880:Piperidines; D018042:Receptors, Neurokinin-3; D015320:Tachykinins; D014665:Vasodilator Agents; C054724:senktide; D013373:Substance P; D015287:Neurokinin B; C091554:SR 142801; D000109:Acetylcholine