Faculty Collaboration Database

Airway synthesis of 20-hydroxyeicosatetraenoic acid: metabolism by cyclooxygenase to a bronchodilator. Am J Physiol 1999 Feb;276(2):L280-8

Date

02/10/1999

Pubmed ID

9950890

DOI

10.1152/ajplung.1999.276.2.L280

Scopus ID

2-s2.0-0032991405 (requires institutional sign-in at Scopus site)   35 Citations

Abstract

Rabbit airway tissue is a particularly rich source of cytochrome P-4504A protein, but very little information regarding the effect(s) of 20-hydroxyeicosatetraenoic acid (20-HETE) on bronchial tone is available. Our studies examined the response of rabbit bronchial rings to 20-HETE and the metabolism of arachidonic acid and 20-HETE from airway microsomes. 20-HETE (10(-8) to 10(-6) M) produced a concentration-dependent relaxation of bronchial rings precontracted with KCl or histamine but not with carbachol. Relaxation to 20-HETE was blocked by indomethacin or epithelium removal, consistent with the conversion of 20-HETE to a bronchial relaxant by epithelial cyclooxygenase. A cyclooxygenase product of 20-HETE also elicited relaxation of bronchial rings. [14C]arachidonic acid was converted by airway microsomes to products that comigrated with authentic 20-HETE (confirmed by gas chromatography-mass spectrometry as 19- and 20-HETE) and to unidentified polar metabolites. [3H]20-HETE was metabolized to indomethacin-inhibitable products. These data suggest that 20-HETE is an endogenous product of rabbit airway tissue and may modulate airway resistance in a cyclooxygenase-dependent manner.

Author List

Jacobs ER, Effros RM, Falck JR, Reddy KM, Campbell WB, Zhu D

Author

William B. Campbell PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Arachidonic Acid
Bronchi
Bronchoconstriction
Bronchodilator Agents
Cyclooxygenase Inhibitors
Cytochrome P-450 Enzyme System
Gas Chromatography-Mass Spectrometry
Hydroxyeicosatetraenoic Acids
In Vitro Techniques
Indomethacin
Male
Microsomes
Prostaglandin-Endoperoxide Synthases
Rabbits