Lipoxin A4-induced release of thromboxane in the guinea-pig lung: studies of its characteristics using lipoxin A4-methyl ester

Abstract

It was the aim of this study to reexamine the contradictory findings regarding the characteristics of LXA4-induced contractions in guinea-pig lung parenchymal strips, with particular respect to release of thromboxane A2 (TXA2). The contraction produced was similar to that evoked by leukotriene C4 (LTC4) regarding both the time course and release of TXA2, measured as TXB2 by RIA of bath-fluid. When release of TXA2 was abolished by pretreatment with the cyclooxygenase inhibitor, indomethacin, the initial component of the contractile response was depressed. Administration of the cysteinyl-leukotriene antagonists FPL 55712 or ICI 198,615 blocked the contractile response to LXA4. Furthermore, FPL 55712 also blocked TXA2-release evoked by LXA4. Maximally precontracted and depolarized preparations retained their ability to release TXA2 in response to LXA4. These findings indicate that LXA4 releases TXA2 by direct activation of a receptor similar to that utilized by the cysteinyl-leukotrienes and that release of TXA2 was not a mere consequence of the contractile response.