Arachidonic acid metabolites do not mediate toluene diisocyanate-induced airway hyperresponsiveness in guinea pigs

Journal Article · Sun May 01 04:00:00 EDT 1988 · Prostaglandins; (United States)

DOI:https://doi.org/10.1016/0090-6980(88)90143-8· OSTI ID:6767702

Gordon, T; Thompson, J E; Sheppard, D

Arachidonic acid metabolites have previously been demonstrated to mediate the airway hyperresponsiveness observed in guinea pigs and dogs after exposure to ozone. Guinea pigs were treated with indomethacin (a cyclooxygenase inhibitor), U-60,257 (piriprost, a 5-lipoxygenase inhibitor), or BW775c (a lipoxygenase and cyclooxygenase inhibitor) and exposed to air or 3 ppm TDI. Airway responsiveness to acetylcholine aerosol was examined 2 h after exposure. In control animals, the provocative concentration of acetylcholine which caused a 200% increase in pulmonary resistance over baseline (PC200) was significantly less (p less than 0.05) after exposure to TDI (8.6 +/- 2.0 mg/ml, geometric mean + geometric SE, n = 10) than after exposure to air (23.9 + 2.5 mg/ml, n = 14). The airway responsiveness to acetylcholine in animals treated with indomethacin or piriprost and exposed to TDI was not different from that of control animals exposed to TDI. Treatment with BW755c enhanced the airway hyperresponsiveness observed in animals exposed to TDI without altering the PC200 of animals exposed to air. The PC200 of animals treated with BW755c and exposed to TDI (2.3 + 0.8 mg/ml, n = 8) was significantly lower than the PC200 of control animals exposed to TDI (p less than 0.025). These results suggest that products of arachidonic acid metabolism are not responsible for TDI-induced airway hyperresponsiveness in guinea pigs. BW755c, however, appears to potentiate the TDI-induced airway hyperresponsiveness to acetylcholine by an as yet unidentified mechanism.

• Research Organization: Univ. of California, San Francisco (USA)
• OSTI ID: 6767702
• Journal Information: Prostaglandins; (United States), Journal Name: Prostaglandins; (United States) Vol. 35:5; ISSN PRGLB
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ACETYLCHOLINE
ALKYLATED AROMATICS
AMINES
AMMONIUM COMPOUNDS
ANIMALS
ARACHIDONIC ACID
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZOLES
BIOLOGICAL EFFECTS
BIOLOGICAL FUNCTIONS
CARBOXYLIC ACIDS
DOGS
DRUGS
ENZYME INHIBITORS
ESTERS
FUNCTIONS
GUINEA PIGS
HETEROCYCLIC COMPOUNDS
HYDROCARBONS
ISOCYANATES
MAMMALS
METABOLITES
MONOCARBOXYLIC ACIDS
NEUROREGULATORS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PARASYMPATHOMIMETICS
PYRAZOLES
QUATERNARY COMPOUNDS
RESPIRATORY SYSTEM
RODENTS
TOLUENE
VERTEBRATES