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-1beta and induces hyperresponsiveness to the tachykinin NK1 receptor agonist [Sar(9),Met(O(2))(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-1beta effects and/or the NGF-induced airway hyperresponsiveness. SR142801 (0.1 microM) abolished the interleukin-1beta (10 ng/ml, 21 degrees 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-1beta-induced airway hyperresponsiveness to [Sar(9),Met(O(2))(11)]SP (0.1 microM) (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-1beta-induced NGF release and airway hyperresponsiveness.
Naline
Emmanuel
E
Research Unit EA220, Université de Versailles, Faculté de Médecine, Pharmacology, Hôpital Foch, 40 rue Worth, 92150 Suresnes, France.
Höglund
Caroline Olgart
CO
Vincent
François
F
Emonds-Alt
Xavier
X
Lagente
Vincent
V
Advenier
Charles
C
Frossard
Nelly
N
D001980:Bronchi / Q000187:drug effects* / Q000502:physiology; D016535:Bronchial Hyperreactivity / Q000139:chemically induced*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D053583:Interleukin-1beta / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D020932:Nerve Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D018042:Receptors, Neurokinin-3 / Q000037:antagonists & inhibitors / Q000502:physiology*
D053583:Interleukin-1beta; D010880:Piperidines; D018042:Receptors, Neurokinin-3; D020932:Nerve Growth Factor; C091554:SR 142801