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Effects of protein kinase and phosphatase inhibitors on bioelectric responses of guinea-pig tracheal epithelium to hyperosmolarity and methacholine (MCh).

Authors
Jing-Y; Van Scott-MR; Fedan-JS
Source
FASEB J 2005 Mar; 19(5)(Part 2):A1549
NIOSHTIC No.
20026713
Abstract
Release of epithelium-derived relaxing factor (EpDRF) is linked to epithelial ion transport, but the mechanistic relationship is unclear. Thus, an apparatus was developed to allow measurement of transepithelial potential differnece (Vt), resistance (Rt), and diameter of perfused trachea. Extraluminal MCh (0.3 :M) contracted, whereas intraluminal (IL) D-mannitol (D-M, 30 mosM) relaxed the tracheas. Both MCh and D-M increased Vt but had no effect on Rt. The PKC inhibitor, chelerythrine (20 :M, IL), decreased basal Vt and inhibited MCh-and D-M-induced hyperpolarization without affect Rt. The JNK inhibitors, SP 600125 (30 :M, IL) and dicumarol (15 :M, IL), potentiated MCh-induced hyperpolarization, but no change in Rt was observed. In contrast, the JNK inhibitors inhibited D-M-induced hyperpolarization, and D-M increased Rt in the presence of the JNK inhibitors. NaAsO2 (300 :M, IL) decreased basal Vt, did not affect MCh responses, but mimicked the effect of the JNK inhibitors on the response to D-M. The phosphatase inhibitor, Na3VO4 (300 :M, IL), increased basal Vt and inhibited MCh- and D-M-induced hyperpolarization; MCh decreased Rt in the presence of Na3VO4. The results suggest that basal Vt is regulated by kinases, and that bioelectric responses that accompany contraction/relaxation responses to MCh and hyperosmolarity may be distinguished by their senstivity to JNK inhibitors.
Keywords
Proteins; Bioelectric-effects; Laboratory-animals; Animals; Animal-studies; Sensitivity-testing; Ion-transport
CODEN
FAJOEC
Publication Date
20050307
Document Type
Abstract; Conference/Symposia Proceedings
Fiscal Year
2005
NTIS Accession No.
NTIS Price
Issue of Publication
5
ISSN
0892-6638
NIOSH Division
HELD
Source Name
The FASEB Journal
State
WV; NC
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