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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).

Authors
Jing-Y; Van Scott-M; Fedan-J
Source
FASEB J 2004 Mar; 18(4)(I):6588
NIOSHTIC No.
20024840
Abstract
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.
Keywords
Laboratory-animals; Laboratory-testing; Animals; Animal-studies; Mechanical-tests; Lung-function; Lung-tissue; In-vitro-study
CODEN
FAJOEC
Publication Date
20040324
Document Type
Conference/Symposia Proceedings; Abstract
Fiscal Year
2004
NTIS Accession No.
NTIS Price
Issue of Publication
4
ISSN
0892-6638
NIOSH Division
HELD
Priority Area
Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease
Source Name
The FASEB Journal, Experimental Biology 2004, Washington, DC, April 17-21, 2004
State
WV
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