Premium
PGE 2 – EP 3 Receptor Signaling Involves Rho‐kinase Pathway in Hyperoxia‐Induced Airway Hyperresponsiveness
Author(s) -
Neziri Burim,
Sopi Ramadan B,
Dreshaj Ismail A,
Beqiraj Qendresa,
Cenaj Asllan,
Kurtishi Ilir,
Krasniqi Avdyl,
Dreshaj Shemsedin,
Jakupaj Muharrem
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1263.6
Subject(s) - fasudil , rho associated protein kinase , hyperoxia , rho kinase inhibitor , contraction (grammar) , methacholine , endocrinology , agonist , medicine , antagonist , chemistry , receptor antagonist , signal transduction , receptor , pharmacology , biochemistry , lung , respiratory disease
Hyperoxic exposure is associated with airway hyperresponsiveness and it was shown that hyperoxia upregulates synthesis of prostaglandin E 2 (PGE 2 ), which induces contraction of airway smooth muscle via EP 1 and EP 3 receptors. It is not clear through which signaling pathway PGE 2 exerts contractile effect on airway smooth muscle under hyperoxic conditions. Therefore, we hypothesized that under hyperoxic condition PGE 2 induces contraction of airway smooth muscle via EP 3 receptors by activating Rho‐kinase signaling pathway. Tracheal cylinders were obtained from 12 days Wistar rat pups exposed to hyperoxia (≥ 95% O 2 ) or room air for seven days. These cylinders were used to study contractile responses evoked by EP 3 agonist (sulprostone, 10 −9 – 10 −5 M); methacholine (MCh, 10 −8 – 10 −4 M) in absence or presence of an EP 3 antagonist (L‐798106, 10 μM) or Rho‐kinase inhibitors (Y‐27632, 10 μM or fasudil, 10 μM). Both, sulprostone and MCh induced dose‐dependent contractile responses of airway smooth muscle, respectively. The contractile responses were significantly higher in preparations obtained from animals exposed to hyperoxia as compared to those obtained from room air controls. These enhanced contractile responses in hyperoxic tissues were reversed by pre‐incubating tissues with Y‐27632 or fasudil. EP 3 antagonist also significantly attenuated contractile responses evoked by sulprostone. The results of this study revealed that PGE 2 – EP 3 receptor signaling involves Rho‐kinase pathway and we speculate that the use of Rho‐kinase inhibitors or EP 3 antagonist could attenuate the contractile effects of PGE 2 and this might be an effective therapeutic approach to reverse hyperoxia‐induced airway hyperresponsiveness. Support or Funding Information Supported by MEST