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Hyperosmolar (HO) solution-induced bioelectric and mechanical responses of guinea-pig isolated, perfused trachea (IPT): effects of MAPK inhibitors.

Authors
Ying-J; Fedan-JS; Van Scott-MR
Source
FASEB J 2003 Mar; 17(5):A1046
NIOSHTIC No.
20023069
Abstract
Exercise causes evaporative water loss in airway surface liquid and airway obstruction in asthmatics. Mucosal application of HO solution to the IPT elicits transepithelial potential difference (Vt) changes preceding epithelium-dependent smooth muscle relaxation mediated by epithelium-derived relaxing factor (EpDRF). We examined the relationship between mucosal HO D-mannitol(D-M)-induced Vt and mechanical responses (changes in inlet - outlet pressure difference; DeltaP) in IPT and examined the possible role of MAPK signaling with mucosally-applied P38, JNK and ERK inhibitors. HO D-M solutions (0- M added to Krebs perfusion solution, 2.7-266.8 mosM) hyperpolarized . Vt below 80 mosM, but depolarized Vt at higher concentrations. Maximum relaxation occurred at -80 mosM, and there was coincidence in the Vt and relaxation dose-response curves to that point. The JNK inhibitor II, SP 600125 (30 11M), inhibited Vt responses to HO D-M but had no effect on relaxation responses to 30 mosM D-M. The ERK inhibitor, PD 98059 (50 uM). had no effect on D-M-induced Vt and relaxation responses. The P38 inhibitor, SKF 86002 (30 uM), had no effect on Vt responses but potentiated HO O-M-induced relaxation. The results indicate that the P38 pathway may be uniquely involved in regulating mechanical responses of the airways to mucosal HO challenge.
Keywords
Airway-obstruction; Respiratory-system-disorders; Pulmonary-system-disorders; Mechanical-properties; Bronchial-asthma; In-vitro-study
CODEN
FAJOEC
Publication Date
20030322
Document Type
Abstract; Conference/Symposia Proceedings
Fiscal Year
2003
NTIS Accession No.
NTIS Price
Issue of Publication
5
ISSN
0892-6638
NIOSH Division
HELD
Priority Area
Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease
Source Name
The FASEB Journal, Experimental Biology 2003, San Diego, California, April 11-15, 2003
State
WV
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