title: Characterization of neurokinin effects and receptor selectivity in human isolated bronchi.
abstract: Sensitive afferent nerves and the neurokinins they release upon activation are considered to be important in controlling bronchomotor tone. Human isolated bronchi respond to neurokinin A (NKA), substance P (SP), and neurokinin B (NKB) with dose-dependent contractions. The order of potency of the three natural neurokinins is NKA greater than SP greater than NKB, suggesting the presence of NK-2 receptors. To further characterize the neurokinin receptors in human bronchi, we used selective agonists for each receptor type (i.e., NK-1, NK-2, and NK-3). In fact, NK-1 selective compounds, [Pro9]SP(1-11) sulfone and [beta-ala4,Sar9]SP(4-11) sulfone, did not induce significant contractions up to 10(-5) M. Similarly, the selective agonist for the NK-3 receptor, [MePhe7]NKB(4-10), was almost inactive. However, the NK-2 selective fragment [Nle]NKA(4-10) was a potent stimulant. The negative log of the peptide concentration that caused 50% of maximal effect (pD2) was 6.99 for NKA and 6.12 for [Nle10]NKA(4-10). Removal of the epithelium significantly enhanced the contractile responses to the three neurokinins and also to the NK-2 selective agonist. Phosphoramidon, an enkephalinase inhibitor, was more potent than epithelium removal in enhancing the contractile responses to these agonists. However, epithelium removal and phosphoramidon did not increase the weak responses to the NK-1 and NK-3 selective compounds. In the presence of phosphoramidon, removal of the epithelium slightly enhanced the contractile responses to NKA and [Nle]NKA(4-10) but not to SP and NKB.(ABSTRACT TRUNCATED AT 250 WORDS)
authors: Department of Pharmacology, Faculty of Medicine, Cochin Hospital, Paris, France.
authors: E
authors: E
authors: Naline
authors: P
authors: P
authors: Devillier
authors: G
authors: G
authors: Drapeau
authors: L
authors: L
authors: Toty
authors: H
authors: H
authors: Bakdach
authors: D
authors: D
authors: Regoli
authors: C
authors: C
authors: Advenier
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D004848:Epithelium / Q000502:physiology; D006020:Glycopeptides / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D015288:Neurokinin A / Q000494:pharmacology*; D015287:Neurokinin B / Q000494:pharmacology*; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism; D013373:Substance P / Q000494:pharmacology
chemical_list: D006020:Glycopeptides; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; D017981:Receptors, Neurotransmitter; D013373:Substance P; D015288:Neurokinin A; D015287:Neurokinin B; D000109:Acetylcholine; C008890:phosphoramidon