Nerve growth factor enhances cough via a central mechanism of action.
Pharmacol Res
; 74: 68-77, 2013 Aug.
Article
en En
| MEDLINE
| ID: mdl-23742790
ABSTRACT
The mechanisms involved in enhanced cough induced by central and inhaled NGF in guinea pigs were investigated. Cough and airway function were assessed by plethysmography following inhaled or intracerebroventricular (i.c.v.) NGF treatment. Expression of TrkA and/or TRPV1 was determined in bronchi and/or brainstem by real-time PCR and immunoblotting. I.c.v. and inhaled NGF enhanced citric acid induced-cough and airway obstruction. Pretreatment (i.c.v.) with antagonists of TrkA (K252a) or TRPV1 (IRTX) significantly reduced both the NGF (i.c.v.) enhanced cough and airway obstruction whereas the NK1 antagonist (FK888) inhibited only cough. The H1 antagonist (cetirizine) did not affect either. Inhaled NGF increased phosphorylation of TrkA receptors in the bronchi but not the brainstem at 0.5h post-treatment. TrkA mRNA was elevated at 0.5h in the bronchi and at 24h in the brainstem while TRPV1 mRNA was elevated from 0.5h to 24h in brainstem and at 24h in the bronchi. Pretreatment (i.c.v.) with IRTX, but not K252a, significantly inhibited the inhaled NGF-enhanced cough. Central NGF administration enhances cough and airway obstruction by mechanisms dependent on central activation of TrkA, TRPV1 and NK1 receptors while inhaled NGF enhances cough via a mechanism dependent on central TRPV1 and not TrkA receptors. These data show that NGF, in addition to its effects on the airways, has an important central mechanism of action in the enhancement of cough. Therefore, therapeutic strategies targeting NGF signaling in both the airways and CNS may be more effective in the management of cough.
Palabras clave
ACSF; ASCIC-3; AUC; BSA; CNS; Cough; H(1); I.c.v.; Inhalation; NGF; NK(1); NTS; PBS; TRPV1; TrkA; acid sensing ion channel 3 protein; area under the curve; artificial cerebrospinal fluid; bovine serum albumin; central nervous system; histamine 1; i.c.v.; intracerebroventricular; nerve growth factor; neurokinin 1; nucleus tractus solitarious; phosphate buffered saline; transient receptor potential vanilloid 1; tyrosine kinase A receptor
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Tos
/
Factor de Crecimiento Nervioso
/
Obstrucción de las Vías Aéreas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Pharmacol Res
Asunto de la revista:
FARMACOLOGIA
Año:
2013
Tipo del documento:
Article
País de afiliación:
Kuwait