title: Neuromodulation mediated by the tachykinin NK3-receptor agonist [MePhe7]-neurokinin B in the isolated perfused lung of nonsensitized nonchallenged and ovalbumin-sensitized and -challenged guinea pig.
abstract: The neuromodulatory action of the tachykinin NK(3)-receptor agonist [MePhe(7)]-neurokinin B ([MePhe(7)]-NKB) was evaluated on vagal stimulation-induced bronchoconstriction in nonsensitized nonchallenged and ovalbumin (OVA)-sensitized and -challenged guinea pig using the isolated perfused lung preparation. Lungs were placed inside a warmed (37°C) glass chamber and suspended from a force displacement transducer (Grass FT-03) with both vagi connected to a stimulating electrode. Isolated lungs were stimulated at a constant voltage (20 V) and pulse duration (5 ms) with electrical stimulation frequencies ranging from 1 to 128 Hz. The authors demonstrated that vagal stimulation produced frequency-dependent bronchoconstriction and [MePhe(7)]-NKB, at a dose (0.1 μM) that does not produce bronchoconstriction by itself, potentiated the vagally induced bronchoconstriction at all frequencies in nonsensitized nonchallenged animals and to a greater extent in OVA-sensitized and -challenged guinea pigs; the potentiations were totally inhibited by the tachykinin NK(3)-receptor antagonist SR 142801 (1 μM). In a second set of experiments, [MePhe(7)]-NKB produced bronchoconstriction in a dose-dependent (1 to 300 μg/mL) manner with similar potencies and maximum responses in nonsensitized nonchallenged (EC(50) = 8.6 ± 1.1 μM; E(Max) = 61.1 ± 3.5 mm Hg) and OVA-sensitized and -challenged (EC(50) = 8.5 ± 1.3 μM; E(Max) = 63.5 ± 3.7 mm Hg) animals. In conclusion, these results demonstrated that [MePhe(7)]-NKB potentiated vagal stimulation-induced bronchoconstriction via the tachykinin NK(3)-receptors and OVA sensitization caused development of airway hyperresponsiveness in these potentiations. However, OVA sensitization had no effect on airway responsiveness of vagal stimulation-and [MePhe(7)]-NKB-induced bronchoconstrictions.
authors.affiliation: In Vivo Pharmacology Department, Merck Research Laboratory,   Kenilworth, New Jersey,   USA.
authors.forename: Michel R
authors.initials: MR
authors.lastname: Corboz
authors.forename: Maria A
authors.initials: MA
authors.lastname: Rivelli
authors.forename: Xiomara
authors.initials: X
authors.lastname: Fernandez
authors.forename: Scott
authors.initials: S
authors.lastname: Greenfeder
mesh_terms: D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology; D004566:Electrodes; D006168:Guinea Pigs; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008297:Male; D015288:Neurokinin A / Q000378:metabolism; D015287:Neurokinin B / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D010047:Ovalbumin / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D018041:Receptors, Neurokinin-2 / Q000378:metabolism; D018042:Receptors, Neurokinin-3 / Q000819:agonists* / Q000378:metabolism*; D018039:Receptors, Tachykinin / Q000378:metabolism; D014630:Vagus Nerve / Q000187:drug effects / Q000378:metabolism; D055536:Vagus Nerve Stimulation / Q000379:methods
chemical_list: D018377:Neurotransmitter Agents; D010880:Piperidines; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; D018039:Receptors, Tachykinin; C080394:neurokinin B, MePhe(7)-; D015288:Neurokinin A; D015287:Neurokinin B; D010047:Ovalbumin; C091554:SR 142801