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

Journal Article · Sun May 01 00:00:00 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), Vol. 35:5
• Country of Publication: United States
• Language: English

Related Subjects

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