Studies on the Identity of Epithelium-Derived Relaxing Factor in Isolated Perfused Trachea Using Pharmacological Agents

Details

• Personal Author:
  Dowdy JA ; Fedan, Jeffery S. ; Johnston RA ; Van Scott MR ; Wu DXY
• Description:
  Hyperosmolar challenge of airway epithelium stimulates the release of epithelium-derived relaxing factor (EpDRF), but the identity of EpDRF is not known. We examined the effects of pharmacological agents on relaxant responses of methacholine (3 x 10(-7) M)-contracted guinea pig perfused trachea to mucosal hyperosmolar challenge using D-mannitol. Responses were inhibited by gossypol (5 x 10(-6) M), an agent with diverse actions, by the carbon monoxide (CO) scavenger hemoglobin (10(-6) M), and by the heme oxygenase (HO) inhibitor zinc (II) protoporphyrin IX (10(-4) M). The HO inhibitor chromium (III) mesoporphyrin IX (10(-4) M) was not inhibitory, and the HO activator heme-L-lysinate (3 x 10(-4) M) did not evoke relaxant responses. The CO donor tricarbonyldichlororuthenium (II) dimer (2.2 x 10(-4) M) elicited small relaxation responses. Other agents without an effect on responses included: apyrase, adenosine, 6-anilino-5,8-quinolinequinone (LY83583), proadifen, MK571, diphenhydramine, glibenclamide, HgCl2, tetrodotoxin, nystatin, alpha-hemolysin, Rp-8-Br-cGMPS, 12-O-tetradecanoylphorbol-13-acetate, cholera toxin, pertussis toxin, thapsigargin, nifedipine, Ca(2+)-free mucosal solution, hydrocortisone, and epidermal growth factor. Cytoskeleton inhibitors, including erythro-9-(2-hydroxyl-3-nonyl)adenine, colchicine, nocodazole, latrunculin B, and cytochalasins B and D, had no effect on relaxation responses. The results suggest provisionally that a portion of EpDRF activity may be due to CO and that the release of EpDRF does not involve cytoskeletal reorganization. [Description provided by NIOSH]
• Subjects:
  Animals Lung Methacholine Compounds Occupational Health Respiratory System Safety
• Keywords:
  Airway-obstruction Airway-resistance Animal-studies Bioelectric-effects Cellular-reactions In-vitro-study Methacholines Pulmonary-system Throat
• ISSN:
  1073-449X
• Document Type:
  Text
• Genre:
  Abstract or Summary ; Proceedings
• Place as Subject:
  Florida ; North Carolina ; OSHA Region 3 ; OSHA Region 4 ; 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:
  169
• Issue:
  7
• NIOSHTIC Number:
  nn:20024739
• Citation:
  Am J Respir Crit Care Med 2004 Apr; 169(7)(Abstracts):A674
• Email:
  jsf2@cdc.gov
• Federal Fiscal Year:
  2004
• NORA Priority Area:
  Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease
• Peer Reviewed:
  False
• Source Full Name:
  American Journal of Respiratory and Critical Care Medicine
• Supplement:
  Abstracts
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:1a3a35de38d6d98bf7678eca244bb43ea324b970fc2cca171e45c6719e609e35fa68401d13b4c1abf57714e86fe414083faa781e96f3edbfaea0b462fb64b931
• Download URL:
  https://stacks.cdc.gov/view/cdc/196377/cdc_196377_DS1.pdf
• File Type:
  [PDF - 538.51 KB ]