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)

Details

• Personal Author:
  Fedan, Jeffery S. ; Jing Y ; Van Scott M
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Animals Laboratories Lung Occupational Health Respiratory System Safety
• Keywords:
  Animal-studies In-vitro-study Laboratory-animals Laboratory-testing Lung-function Lung-tissue Mechanical-tests
• ISSN:
  0892-6638
• Document Type:
  Text
• Genre:
  Proceedings ; Abstract
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  18
• Issue:
  4
• NIOSHTIC Number:
  nn:20024840
• Citation:
  FASEB J 2004 Mar; 18(4)(I):6588
• Federal Fiscal Year:
  2004
• NORA Priority Area:
  Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease
• Peer Reviewed:
  False
• Part Number:
  I
• Source Full Name:
  The FASEB Journal, Experimental Biology 2004, Washington, DC, April 17-21, 2004
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:01460554be7e24ec7eb764754825cfa9c9b757b8d7bd2c7e191eecba420c03e815c37fd721b09740ce2b28381db07553c7d172197d7088865ca87a29328e4f8a
• Download URL:
  https://stacks.cdc.gov/view/cdc/196456/cdc_196456_DS1.pdf
• File Type:
  [PDF - 912.84 KB ]