title: Tachykinin receptors mediating contraction of guinea pig lung strips.
abstract: The aim of this study was to determine which tachykinin receptors mediate contraction in guinea pig lung parenchymal strips in vitro. Contraction caused by selective neurokinin-1 (NK-1), neurokinin-2 (NK-2), and neurokinin-3 (NK-3) receptor agonists and the natural agonists substance P (SP) and neurokinin A (NKA) was measured in the absence or presence of the NK-1 antagonist CP-96,345 and/or the NK-2 antagonist SR 48968. The NK-1 agonist [Sar9, Met(O2)11]-substance P and the NK-2 agonist [Nle10]-neurokinin A 4-10 caused similar concentration-dependent contractions that were inhibited by CP-96,345 and SR 48968, respectively. The NK-3 agonist [MePhe7]-neurokinin B also caused contraction, albeit at 10-fold higher concentrations, and this contraction was unaffected by either the NK-1 or NK-2 antagonist or the combination of both antagonists. Either CP-96,345 or SR 48968 alone had little effect on NKA-mediated contraction but administration of both antagonists virtually eliminated force generation. SP-induced tension was partially inhibited by SR 48968 and unaffected by CP-96,345. A second NK-1 receptor antagonist CP-99,994 also had no effect on SP-mediated tension. Therefore, NK-1, NK-2, and NK-3 agonists can all cause contraction in guinea pig lung strips, NKA-induced tension is mediated by both NK-1 and NK-2 receptors, and SP-induced contraction is mediated in part by NK-2 receptors. Both the SP and the [MePhe7]-neurokinin B data suggest that activation of a third neurokinin receptor subtype that is unaffected by an NK-1 receptor antagonist or an NK-2 receptor antagonist can cause contraction in guinea pig lung strips.
authors.affiliation: Physiology Program, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: C R
authors.initials: CR
authors.lastname: Killingsworth
authors.forename: S A
authors.initials: SA
authors.lastname: Shore
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D004151:Dipeptides / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008168:Lung; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000502:physiology*; D015288:Neurokinin A / Q000031:analogs & derivatives / Q000494:pharmacology; D015287:Neurokinin B / Q000031:analogs & derivatives / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D018040:Receptors, Neurokinin-1 / Q000187:drug effects / Q000502:physiology*; D018041:Receptors, Neurokinin-2 / Q000187:drug effects / Q000502:physiology*; D018039:Receptors, Tachykinin / Q000187:drug effects / Q000502:physiology*; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D014132:Trachea
chemical_list: D001549:Benzamides; D001713:Biphenyl Compounds; D004151:Dipeptides; D010446:Peptide Fragments; D010880:Piperidines; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D018039:Receptors, Tachykinin; C080394:neurokinin B, MePhe(7)-; C061060:neurokinin A (4-10), Nle(10)-; C062618:substance P, Sar(9)-Met(O2)(11)-; C080755:3-(2-methoxybenzylamino)-2-phenylpiperidine; D013373:Substance P; C073839:SR 48968; C062344:SCH 32615; D015288:Neurokinin A; D015287:Neurokinin B; D000109:Acetylcholine; C066892:CP 96345