Am. J. Respir. Cell Mol. Biol., Vol 13, No. 4, 10 1995, 410-417.
Eicosanoid production in rabbit tracheal epithelium by adenine nucleotides: mediation by P2-purinoceptors
MO Aksoy, M Borenstein, XX Li and SG Kelsen
Department of Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
Adenosine triphosphate (ATP) acting through epithelial nucleotide receptors
exerts multiple physiologic actions on airway mucociliary clearance and
caliber. However, the effect of ATP on arachidonate metabolism in the
airway remains unknown. In this study, the ability of ATP to regulate
eicosanoid production was studied in vitro in full- thickness rabbit
tracheal strips and separately in rabbit epithelial explant cultures. In
the freshly isolated strips, ATP increased prostaglandin E2 (PGE2) release
in a dose-dependent fashion, with an activation threshold at 10 microM ATP
and a 3.5-fold increase in PGE2 output at 1 mM ATP. Epithelium removal
decreased 1 mM ATP-evoked PGE2 release by 68%. Reverse-phase, high-pressure
liquid chromatography (HPLC) of media from 3H-arachidonic acid-incubated
epithelial explants exposed to 1 mM ATP demonstrated increased output of
the cyclooxygenase products PGE2 and prostaglandin F2a (PGF2a). Other
identifiable eicosanoids did not increase. The concentration-response for
ATP- induced PGE2 release by explants was similar to that of tracheal
strips. PGE2 release by 1 mM ATP was 27% of that elicited by ionomycin (10
microM) and was markedly inhibited by indomethacin (10 microM).
Purinoceptor agonist-stimulated PGE2 release by the epithelium yielded a
rank order of potency of uridine triphosphate (UTP) > or = ATP > 2-
methylthio-ATP (2MeSATP) >> alpha,beta-methyleneadenosine-5'-
triphosphate (AMP-CPP) > or = adenosine. These results indicate that
ATP, acting primarily through an epithelial P2-purinoceptor similar to the
P2a subtype, stimulates eicosanoid metabolism in rabbit airway epithelium
via the cyclooxygenase pathway, producing PGE2 as the predominant species.
