Role of tachykinin NK3 receptors in the release and effects of nerve growth factor in human isolated bronchi

The nerve growth factor (NGF) is a neurotrophic factor essential for the development and survival of neurons. It has also been identified as a mediator of inflammation and can cause airway hyperresponsiveness [Frossard et al., Eur. J. Pharmacol. 500, 453 (2004)]. Evidence in rodents suggests a link between tachykinins, the sensory nerves, and NGF. Recent evidence shows that NGF is released by the proinflammatory cytokine interleukin-1β and induces hyperresponsiveness to the tachykinin NK1 receptor agonist [Sar9,Met(O2)11]SP in isolated human bronchi. The aim of this study was to determine the role of sensory nerves through the effect of the tachykinin NK3 receptor antagonist SR142801 in the interleukin-1β effects and/or the NGF-induced airway hyperresponsiveness. SR142801 (0.1 μM) abolished the interleukin-1β (10 ng/ml, 21 °C, 15 h)-induced increased NGF release from isolated human bronchi in vitro (P < 0.05). In organ bath studies, SR142801 also abolished the interleukin-1β-induced airway hyperresponsiveness to [Sar9,Met(O2)11]SP (0.1 μM) (P < 0.05). SR142801 also inhibited the NGF-induced airway hyperresponsiveness (P < 0.01). This study suggests tachykininergic sensory nerves to be involved in the interleukin-1β-induced NGF release and airway hyperresponsiveness.