The role of sensory nerve endings in nerve growth factor-induced airway hyperresponsiveness to histamine in guinea-pigs

Citation
A. De Vries et al., The role of sensory nerve endings in nerve growth factor-induced airway hyperresponsiveness to histamine in guinea-pigs, BR J PHARM, 134(4), 2001, pp. 771-776
Citations number
52
Categorie Soggetti
Pharmacology & Toxicology
Journal title
BRITISH JOURNAL OF PHARMACOLOGY
ISSN journal
00071188 → ACNP
Volume
134
Issue
4
Year of publication
2001
Pages
771 - 776
Database
ISI
SICI code
0007-1188(200110)134:4<771:TROSNE>2.0.ZU;2-H
Abstract
1 Nerve growth factor induces an airway hyperresponsiveness in vivo in guin ea-pigs, as we have shown previously. Since antagonizing the neurokinin-1 ( NK1) receptor can prevent this NGF-induced airway hyperresponsiveness and s ince sensory nerves release tachykinins, we investigated the role of sensor y nerves in the NGF-induced airway hyperresponsiveness. 2 We used isolated tracheal rings from guinea-pigs to measure tracheal cont ractility. In these rings sensory nerve endings are present, but these endi ngs lack any contact with their cell bodies. 3 In this in vitro system, NGF dose-dependently induced a tracheal hyperres ponsiveness to histamine. The NK1 receptor antagonist SR140333 could block the induction of tracheal hyperresponsiveness. 4 To further investigate the involvement of sensory nerve endings we used t he cannabinoid receptor 1 (CB1) agonist R-methanandamide to inhibit excitat ory events at the nerve terminal. The CB1 receptor agonist was capable of b locking the tracheal hyperresponsiveness to NGF in the isolated system, as well as the airway hyperresponsiveness to NGF in vivo. 5 This indicates that NGF can induce an increase in airway responsiveness i n the absence of sensory nerve cell bodies. NGF may act by increasing subst ance P release from sensory nerve endings, without upregulation of substanc e P in the neurons. Substance P in its turn is responsible for the inductio n of the NGF-induced airway hyperresponsiveness.