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1 Department of Physiology,
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
106 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.
bronchi; bronchodilation; eicosanoid; arachidonic acid; cytochrome P-450
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