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)   34 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

Authors

William B. Campbell PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Elizabeth R. Jacobs MD Emeritus Professor in the Medicine 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