Biological activity of leukotriene sulfones on respiratory tissues

Abstract

The biological activity of synthetic leukotriene C 4, D 4 and E 4 sulfone has been determined in respiratory smooth muscle in vitro and in vivo . The sulfones of LTC 4, LTD 4 and LTE 4 were potent contractile agonists on indomethacin-treated guinea pig tracheal chains with respective pD 2-values of 8.2, 8.0 and 7.9. Contractions were submaximal (75–85% of the cholinergic maximum), slow in onset, prolonged in duration, slowly reversed by washing (compared to acetylcholine or histamine) and were partially reversed by 2μM FPL-55712. The sulfones of LTC 4, LTD 4 and LTD 4 also contracted indomethacin-treated guinea pig parenchyma (respective pD 2′s of 7.9 8.2 and 7.8) and rat parenchyma (respective pD 2′s of 7.1, 7.2 and 7.2) but were inactive on rat trachea (0.01–2.0 gmM). When administered intravenously to anaesthetized guinea pigs, the sulfones of LTD 4, LTE 4 and to a lesser degree LTC 4 (respective ED 50′s - 0.5; 2.0 and 4.6 μg/kg) elicited dose-dependent increases in inflation pressure which were antagonized by FPL-55712 and indomethacin. Leukotriene C 4, D 4 and E 4 sulfones display a qualitatively similar profile of biological activity to that of their corresponding sulfides.