Neuromodulation mediated by the tachykinin NK 3-receptor agonist MePhe 7-neurokinin B in the isolated perfused lung of nonsensitized nonchallenged and ovalbumin-sensitized and -challenged guinea pig

摘要

The neuromodulatory action of the tachykinin NK 3-receptor agonist MePhe 7-neurokinin B (MePhe 7-NKB) was evaluated on vagal stimulationinduced 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 stimulationinduced 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 stimulationand MePhe 7-NKBinduced bronchoconstrictions.