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)) h as 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 su sceptible to TXA(2). In order to determine the role of TXA(2) in the c entral and peripheral airways, we compared the effect of a TXA(2) anta gonist on tracheal strips to its effect on parenchymal strips of guine a-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 degrees C. After equilibration for 60 min in Krebs so lution, the strip was contracted by exposure to 10(-5) M of acetylchol ine (ACh). Sixty minutes after ACh was eliminated, the concentration-r esponse 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 contracti on 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 o n the LTD(4)-induced contraction. However, in parenchymal strips, BAY u3405 significantly suppressed the contractile response to LTD(4). The se results suggest that in the central airway LTD(4) contracts smooth muscle directly, but that in the peripheral airway LTD(4) induces smoo th muscle contraction both directly and indirectly, via TXA(2).