title: Tachykinin receptors and noncholinergic bronchoconstriction in the guinea-pig isolated bronchi.
abstract: The aim of the study was to assess which type(s) of tachykinin receptor mediate the noncholinergic bronchoconstriction produced by activation (electrical field stimulation) of capsaicin-sensitive primary afferents in epithellum-denuded guinea-pig isolated bronchi. Experiments with natural and synthetic tachykinin agonists indicated the presence of both NK-1 and NK-2 receptors at this level. Experiments with the putative NK-1 (L668, 169) or NK-2 (MEN 10,207, MEN 10,376, L659,877, and R396) selective antagonists against NK-1 and NK-2 selective agonists further supported this conclusion. All the tachykinin antagonists tested reduced the noncholinergic bronchoconstriction to field stimulation with the order of potency MEN 10,207 = MEN 10,376 greater than L659,877 greater than L668,169 congruent to R396. In the presence of peptidase inhibitors, the activity of MEN 10,376 toward the noncholinergic bronchoconstriction was slightly reduced, whereas that of L668,169 was increased. These findings demonstrate that both NK-1 and NK-2 receptors mediate the noncholinergic constriction produced by endogenous tachykinins in guinea-pig bronchi and that the relative contribution of NK-2 receptors is greater than that of NK-1. These findings implicate a major role for neurokinin A rather than for substance P as an endogenous bronchoconstrictor in the guinea-pig isolated bronchi. In the presence of peptidase inhibitors, the relative contribution of NK-1 receptors is increased.
authors.affiliation: Pharmacology Department, A Menarini Pharmaceuticals, Florence, Italy.
authors.forename: C A
authors.initials: CA
authors.lastname: Maggi
authors.forename: R
authors.initials: R
authors.lastname: Patacchini
authors.forename: P
authors.initials: P
authors.lastname: Rovero
authors.forename: P
authors.initials: P
authors.lastname: Santicioli
mesh_terms: D000818:Animals; D001980:Bronchi / Q000294:innervation*; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology*; D004558:Electric Stimulation; D006168:Guinea Pigs; D008297:Male; D015288:Neurokinin A / Q000502:physiology; D009475:Neurons, Afferent / Q000502:physiology; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D018039:Receptors, Tachykinin; D013373:Substance P / Q000502:physiology; D015320:Tachykinins / Q000037:antagonists & inhibitors* / Q000187:drug effects
chemical_list: D017981:Receptors, Neurotransmitter; D018039:Receptors, Tachykinin; D015320:Tachykinins; D013373:Substance P; D015288:Neurokinin A