Effects of NZ-107 on Tracheal Responses to Adenosine in the Guinea Pig.

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We have investigated the effect of NZ-107, an inhibitor of bronchoconstriction induced by slow reacting substance of anaphylaxis (SRS-A), on tracheal responses to adenosine in the guinea pig. In the presence of an adenosine uptake inhibitor, dipyridamole (1 μM), NZ-107 (0.3-1 μM) enhanced adenosine-induced relaxation in 30 nM leukotriene D4 (LTD4)-precontracted trachea, whereas aminophylline (AP, 10-30 μM), an adenosine receptor antagonist, markedly inhibited it. NZ-107 (1 μM) also enhanced the relaxation induced by forskolin, an adenylate cyclase activator, but not that by nitroprusside (NP), a guanylate cyclase activator. AP (30 μM) affected neither forskolin nor NP-induced relaxation. NZ-107 (1 μM) and AP (30 μM) inhibited to about the same extent the contractile response to an adenosine A1 receptor agonist, the R(-)-enantiomer of N6-(2-phenylisopropyl)-adenosine (R-PIA). The R-PIA-induced contraction was completely blocked by 5 μM indomethacin. NZ-107 (1 μM) did not affect the contraction induced by PGD2, but significantly reduced that of PGF2α. AP (30 μM) had no effect on PGF2α- and PGD2-induced contractions. These results suggest that NZ-107 may have a unique profile for adenosine responses in bronchial asthma.
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