The Effect of Ion Transport Inhibitors on the Bioelectric Responses of Guinea-Pig Tracheal-Epithelium to Hypertonic D-Mannitol Solution

Details

• Personal Author:
  Fedan, Jeffery S. ; Johnston RA ; Rengasamy A ; Van Scott MR
• Description:
  Elevation of serosal or mucosal tonicity induces the release of the non-nitric oxide, non-prostanoid epithelium-derived relaxing factor (EpDRF) from guinea-pig tracheal epithelium, which subsequently diffuses to the underlying airway smooth muscle to initiate relaxation. Hypertonicity-induced smooth muscle relaxation via EpDRF is preceeded by a depolarization of the transepithelial potential difference. This study sought to characterize further the ion channels and/or transporters involved in the response of guinea-pig tracheal epithelium to hypertonic solution by determining the effects of inhibitors on transepithelial short-circuit current (Isc) responses. Isc responses of tracheal segments were measured in vitro using a Ussing chamber. Methacholine (3x10^-7 M) was added to the serosal surface to mimic conditions used in previous studies of EpDRF. Hypertonic D-mannitol solution (120mOsm) added to the mucosal solution decreased the Isc. Pretreatment with amiloride (3x10^-5 M; mucosal), NPPB (10^-4 M; mucosal), or bumetanide (10^-5 M; serosal) inhibited 30 +/- 2%, 77 +/- 8% or 7 +/- 2% of the baseline Isc, respectively. Amiloride inhibited 30 +/- 10% of the Isc induced by D-mannitol. NPPB almost completely abolished the Isc induced by D-mannitol while bumenatide inhibited 34 +/- 9% of the Isc response. Iberiotoxin (10^-7 M; mucosal and serosal) had no apparent effect. Ouabain (10^-5 M serosal) itself caused a progressive reduction in Isc which prevented assessment of the response to D-mannitol. These results indicate that apical membrane Na* and CL- channels and the basolateral Na*-K*- 2CL- cotransporter mediate the epithelial response to elevated mucosal tonicity. [Description provided by NIOSH]
• Subjects:
  Animals Laboratories Methacholine Compounds Musculoskeletal System Occupational Health Safety
• Keywords:
  Animal Studies Bioelectric Effects In Vitro Studies Ion Transport Laboratory Animals Methacholines Muscles Oxides
• ISSN:
  1073-449X
• Document Type:
  Text
• Genre:
  Abstract or Summary
• 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:
  163
• Issue:
  5
• NIOSHTIC Number:
  nn:20021343
• Citation:
  Am J Respir Crit Care Med 2001 Apr; 163(5)(2)(Suppl):A659
• Federal Fiscal Year:
  2001
• Peer Reviewed:
  False
• Part Number:
  2
• Source Full Name:
  American Journal of Respiratory and Critical Care Medicine. Abstracts of the American Thoracic Society 2001 International Conference, May 18-23, 2001, San Francisco, California
• Supplement:
  Suppl
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:78ed34a30aa56fe71a28e6f75da40c50061fc0ed5ea7f8b871885fb921ec2050b85f8e65247c8408ebbabf71db79d60768d5548715fcb36f349773a8ea0012dd
• Download URL:
  https://stacks.cdc.gov/view/cdc/198701/cdc_198701_DS1.pdf
• File Type:
  [PDF - 153.54 KB ]