Thromboxane A 2 antagonist inhibits leukotriene D 4-induced smooth muscle contraction in guinea-pig lung parenchyma, but not in trachea

Abstract

Although the bronchoconstriction induced by leukotriene D 4 (LTD 4) has been reported to be partly mediated by thromboxane A 2 (TXA 2) in the guinea-pig airway, it is not known which part of the airway is susceptible to TXA 2. In order to determine the role of TXA 2 in the central and peripheral airways, we compared the effect of a TXA 2 antagonist on tracheal strips to its effect on parenchymal strips of guinea-pigs. Tracheal and parenchymal strips were mounted in a 3.5 ml organ bath filled with Krebs-Henseleit solution aerated with 95% O 2, 5% CO 2 and kept at 37°C. After equilibration for 60 min in Krebs solution, the strip was contracted by exposure to 10 −5 M of acetylcholine (ACh). Sixty minutes after ACh was eliminated, the concentration-response curve to LTD 4 (10 −9 M–10 −7 M) was obtained, and the LTD 4-induced contractions were expressed as the percent of the contraction evoked by 10 −5 M of ACh. We measured the contractile response to LTD 4 in the presence or absence of the TXA 2 antagonist, BAY u3405 (10 −8 M–10 −6 M). In the tracheal strips, BAY u3405 had no effect on the LTD 4-induced contraction. However, in parenchymal strips, BAY u3405 significantly suppressed the contractile response to LTD 4. These results suggest that in the central airway LTD 4 contracts smooth muscle directly, but that in the peripheral airway LTD 4 induces smooth muscle contraction both directly and indirectly, via TXA 2.