Effects of NZ-107 on tracheal responses to adenosine in the guinea pig.
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 microM), NZ-107 (0.3-1 microM) enhanced adenosine-induced relaxation in 30 nM leukotriene D4 (LTD4)-precontracted trachea, whereas aminophylline (AP, 10-30 microM), an adenosine receptor antagonist, markedly inhibited it. NZ-107 (1 microM) also enhanced the relaxation induced by forskolin, an adenylate cyclase activator, but not that by nitroprusside (NP), a guanylate cyclase activator. AP (30 microM) affected neither forskolin- nor NP-induced relaxation. NZ-107 (1 microM) and AP (30 microM) 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 microM indomethacin. NZ-107 (1 microM) did not affect the contraction induced by PGD2, but significantly reduced that of PGF2 alpha. AP (30 microM) had no effect on PGF2 alpha- and PGD2-induced contractions. These results suggest that NZ-107 may have a unique profile for adenosine responses in bronchial asthma.
Yamamoto
A
A
Shiraoka Research Station of Biological Science, Nissan Chemical Ind., Co., Ltd., Saitama, Japan.
Shikada
K
K
Iwama
T
T
Sakashita
M
M
Hibi
M
M
Tanaka
S
S
D000241:Adenosine / Q000494:pharmacology*; D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D001249:Asthma / Q000188:drug therapy; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D011724:Pyridazines / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism
D011724:Pyridazines; C062698:NZ 107; D000628:Aminophylline; D000241:Adenosine