Thromboxane A₂ antagonist inhibits leukotriene D₄-induced smooth muscle contraction in guinea-pig lung parenchyma, but not in trachea

Although the bronchoconstriction induced by leukotriene D₄ (LTD₄) has been reported to be partly mediated by thromboxane A₂ (TXA₂) in the guinea-pig airway, it is not known which part of the airway is susceptible to TXA₂. In order to determine the role of TXA₂ in the central and peripheral airways, we compared the effect of a TXA₂ 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% O₂, 5% CO₂ 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 LTD₄ (10^-9 M^-10-7 M) was obtained, and the LTD₄-induced contractions were expressed as the percent of the contraction evoked by 10^-5 M of ACh. We measured the contractile response to LTD₄ in the presence or absence of the TXA₂ antagonist, BAY u3405 (10^-8 M^-10^-6 M). In the tracheal strips, BAY u3405 had no effect on the LTD₄-induced contraction. However, in parenchymal strips, BAY u3405 significantly suppressed the contractile response to LTD₄. These results suggest that in the central airway LTD₄ contracts smooth muscle directly, but that in the peripheral airway LTD₄ induces smooth muscle contraction both directly and indirectly, via TXA₂.