Hyperosmolar Solution Effects in Guinea Pig Airways. III. 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 ; 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, (E)-3-[[[3-[2-(7-chloro-2-quinolinyl)ethenyl]phenyl][[3-(dimethylamino)-3-oxopropyl]thio]methyl]thio]-propanoic acid (MK 571), diphenhydramine, glibenclamide, HgCl2, tetrodotoxin, nystatin, alpha-hemolysin, 8-bromoguanosine 3',5'-cyclic monophosphothioate, Rp-isomer, 12-O-tetradecanoylphorbol-13-acetate, cholera toxin, pertussis toxin, thapsigargin, nifedipine, Ca(2+)-free mucosal solution, hydrocortisone, and epidermal growth factor. Cytoskeleton inhibitors, includingerythro-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:
  0022-3565
• Document Type:
  Text
• Genre:
  Journal Article ; Journal Article
• Place as Subject:
  North Carolina ; OSHA Region 3 ; OSHA Region 4 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH) ; National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division ; HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health ; Workplace Safety & Health
• Location:
  North America ; North America
• Pages in Document:
  30-36
• Volume:
  308
• Issue:
  1
• NIOSHTIC Number:
  nn:20024232
• Citation:
  J Pharmacol Exp Ther 2004 Jan; 308(1):30-36
• Contact Point Address:
  Dr. Jeffrey S. Fedan, Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505-2888, USA
• Email:
  jsf2@cdc.gov
• Federal Fiscal Year:
  2004
• NORA Priority Area:
  Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease ; Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease
• Peer Reviewed:
  True
• Source Full Name:
  Journal of Pharmacology and Experimental Therapeutics
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:5acb5ea0a3cd37b4e3ac5e1d3158cd9e892cf1e97311e1a69cfdd519ed2cfcce622ab6cc32fbfbf2df25181438233e10b0c77435f1cbdba149cdb05310f92c2b
• Download URL:
  https://stacks.cdc.gov/view/cdc/196146/cdc_196146_DS1.pdf
• File Type:
  [PDF - 1.14 MB ]