Effects of protein kinase (PK) inhibitors on bioelectric and mechanical responses of guinea-pig isolated, perfused trachea (PT) to hyperosmolar (HO) D-mannitol (D-M).
Jing-Y; Van Scott-M; Fedan-J
FASEB J 2004 Mar; 18(4)(I):6588
Exercise causes evaporative water loss and hyperosmolarity in airway surface liquid. Mucosal application of HO DM to the PT elicits transepithelial potential difference (Vt) changes and epithelium-dependent airway smooth muscle (SM) relaxation mediated by epithelium-derived relaxing factor. We examined the possible roles of PKs, which are reported to have regulatory effects on epithelial ion transport, on 30 mosM DM-induced Vt and relaxation responses. The PK inhibitors applied mucosally were: chelerythrine (PKC inhibitor), LY 294002 (PI3K inhibitor), KN62 (CaMKII inhibitor) and ML7 (MLCK inhibitor). All PK inhibitors caused depolarization upon application. Chelerythrine inhibited methacholine (MCh)- and DM-induced hyperpolarization responses; it also caused SM contraction. LY 294002 did not affect Vt responses to MCh or D-M, but inhibited MCh-induced SM contraction. KN62 and ML7 had no effect on the bioelectric and mechanical responses to MCh or DM. The phosphatase inhibitor, Na3VO4, caused hyperpolarization and inhibited DM-induced hyperpolarization and MCh-induced contraction responses. None of the tested inhibitors had any effect on DM-induced SM relaxation response. The results indicate that a common PK signaling pathway is not involved in both airway bioelectric and mechanical responses to HO challenge.
Laboratory-animals; Laboratory-testing; Animals; Animal-studies; Mechanical-tests; Lung-function; Lung-tissue; In-vitro-study
Conference/Symposia Proceedings; Abstract
Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease
The FASEB Journal, Experimental Biology 2004, Washington, DC, April 17-21, 2004