Hyperosmolar (HO) solution-induced bioelectric and mechanical responses of guinea-pig isolated, perfused trachea (IPT): effects of MAPK inhibitors.
Ying-J; Fedan-JS; Van Scott-MR
FASEB J 2003 Mar; 17(5):A1046
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.
Airway-obstruction; Respiratory-system-disorders; Pulmonary-system-disorders; Mechanical-properties; Bronchial-asthma; In-vitro-study
Abstract; Conference/Symposia Proceedings
Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease
The FASEB Journal, Experimental Biology 2003, San Diego, California, April 11-15, 2003