Eicosanoid production in rabbit tracheal epithelium by adenine nucleotides: mediation by P2-purinoceptors

American Journal of Respiratory Cell and Molecular Biology
M O AksoyS G Kelsen

Abstract

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-st...Continue Reading

Citations

Jun 9, 1999·The Journal of Allergy and Clinical Immunology·M O AksoyS G Kelsen
Mar 30, 2010·Acta Physiologica·G BurnstockA Verkhratsky
Aug 14, 2012·Pharmacological Reviews·Geoffrey BurnstockJean-Pierre Timmermans
Jun 15, 2011·Physiology·Ye Chun RuanHsiao Chang Chan
Jun 12, 2003·American Journal of Physiology. Renal Physiology·Brett D WelchBellamkonda K Kishore
Jul 4, 2001·American Journal of Physiology. Lung Cellular and Molecular Physiology·C N FortnerR J Paul

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