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

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% CO2 and kept at 37 degrees 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).