5-oxo-6-8-11-14-eicosatetraenoic-acid and 14-15-epoxy-5-8-11-eicosatrienoic-acid

The reactivity and Ca2+ sensitivity of fresh as well as organ-cultured guinea pig bronchi challenged with 5-oxo-ETE and 14,15-EET were compared. Tension measurements, performed on fresh and 3-day cultured bronchi, revealed that the contractile responses to 5-oxo-ETE were largely increased in cultured explants, while 14,15-EET induced larger relaxations on Carbamylcholine (CCh) pre-contracted explants. In fresh bronchi, the contractile responses to 5-oxo-ETE were inhibited by 10 microM indomethacin whereas the relaxing responses induced by 14,15-EET were amplified in the presence of COX inhibitors. COX down expression resulted in a lack of indomethacin effect in cultured explants. One micromolar 5-oxo-ETE increased Ca2+ sensitivity in beta-escin-permeabilized cultured explants, while 1 microM Y-27632 abolished this hypersensitivity. In contrast, 1 microM 14,15-EET significantly reduced the Ca2+ hypersensitivity developed by cultured bronchi. In conclusion, pre-treatment of cultured guinea pig bronchi for 48 h with these eicosanoids modifies the pharmacological responsiveness and Ca2+ sensitivity of these cultured explants.

Topics: 8,11,14-Eicosatrienoic Acid; Animals; Arachidonic Acids; Bronchi; Calcium; Cyclooxygenase Inhibitors; Female; Guinea Pigs; Male; Organ Culture Techniques