| dc.creator | Insuela, Daniella B. R. | |
| dc.creator | Daleprane, Julio B. | |
| dc.creator | Coelho, Luciana P. | |
| dc.creator | Silva, Adriana R. | |
| dc.creator | Silva, Patrícia M. R. e | |
| dc.creator | Martins, Marco A. | |
| dc.creator | Carvalho, Vinicius F. | |
| dc.date | 2016-07-07T17:06:25Z | |
| dc.date | 2016-07-08T18:49:09Z | |
| dc.date | 2016-07-07T17:06:25Z | |
| dc.date | 2016-07-08T18:49:09Z | |
| dc.date | 2015 | |
| dc.date.accessioned | 2023-09-26T22:48:04Z | |
| dc.date.available | 2023-09-26T22:48:04Z | |
| dc.identifier | INSUELA, Daniela B. R. et al. Glucagon induces airway smooth muscle relaxation by nitric oxide and prostaglandin E2. Journal of Endocrinology, v.225, p.205-217, June 2015. | |
| dc.identifier | 0022-0795 | |
| dc.identifier | https://www.arca.fiocruz.br/handle/icict/14825 | |
| dc.identifier | 10.1530/JOE-14-0648 | |
| dc.identifier | 1479-6805 | |
| dc.identifier.uri | https://repositorioslatinoamericanos.uchile.cl/handle/2250/8883350 | |
| dc.description | Glucagon is a hyperglycemic pancreatic hormone that has been shown to provide a
beneficial effect against asthmatic bronchospasm. We investigated the role of this hormone
on airway smooth muscle contraction and lung inflammation using both in vitro and in vivo
approaches. The action of glucagon on mouse cholinergic tracheal contraction was
studied in a conventional organ bath system, and its effect on airway obstruction was also
investigated using the whole-body pletysmographic technique in mice. We also tested the
effect of glucagon on lipopolysaccharide (LPS)-induced airway hyperreactivity (AHR) and
inflammation. The expression of glucagon receptor (GcgR), CREB, phospho-CREB, nitric
oxide synthase (NOS)-3, pNOS-3 and cyclooxygenase (COX)-1 was evaluated by western blot,
while prostaglandin E2 (PGE2) and tumour necrosis factor-a were quantified by
enzyme-linked immunoassay and ELISA respectively. Glucagon partially inhibited carbacholinduced
tracheal contraction in a mechanism clearly sensitive to des-His1-[Glu9]-glucagon
amide, a GcgR antagonist. Remarkably, GcgR was more expressed in the lung and trachea
with intact epithelium than in the epithelium-denuded trachea. In addition, the
glucagon-mediated impairment of carbachol-induced contraction was prevented by either
removing epithelial cells or blocking NOS (L-NAME), COX (indomethacin) or COX-1
(SC-560). In contrast, inhibitors of either heme oxygenase or COX-2 were inactive.
Intranasal instillation of glucagon inhibited methacholine-induced airway obstruction by a
mechanism sensitive to pretreatment with L-NAME, indomethacin and SC-560.
Glucagon induced CREB and NOS-3 phosphorylation and increased PGE2 levels in the lung
tissue without altering COX-1 expression. Glucagon also inhibited LPS-induced AHR and
bronchoalveolar inflammation. These findings suggest that glucagon possesses
airway-relaxing properties that are mediated by epithelium-NOS-3-NO- and COX-1-PGE2-
dependent mechanisms. | |
| dc.format | application/pdf | |
| dc.language | eng | |
| dc.publisher | BioScientifica | |
| dc.rights | open access | |
| dc.subject | Endocrinologia | |
| dc.subject | Glucagon | |
| dc.subject | Pneumonia | |
| dc.subject | Contração muscular | |
| dc.subject | Vias aéreas | |
| dc.subject | Endocrinololy | |
| dc.subject | Glucagon | |
| dc.subject | Lung inflammation | |
| dc.subject | Airway smooth muscle contraction | |
| dc.title | Glucagon induces airway smooth muscle relaxation by nitric oxide and prostaglandin E2 | |
| dc.type | Article | |
