Effect of an anti-SRS-A agent, NZ-107, on airway responses induced by ovalbumin and A23187 in the guinea-pig.
The effects of the anti-SRS-A agent NZ-107 on antigen-(ovalbumin) and calcium ionophore A23187-induced airway responses in the guinea-pig have been investigated. In the presence of 5 microM indomethacin, NZ-107 (3 microM) did not affect the peak response in ovalbumin-induced contraction but did inhibit the prolonged response following the peak response in the tracheal strip. A higher concentration of NZ-107 (10 microM) completely blocked both peak and prolonged responses. Inhibitory effects of NZ-107 on ovalbumin responses were less in the lung parenchymal strip. The potency of NZ-107 in inhibiting ovalbumin-induced tracheal contraction was not changed in the absence of indomethacin but was reduced in the presence of 45 mM serine-borate, an inhibitor of the conversion of LTC4 to LTD4. NZ-107 inhibited A23187-induced contractions in both tracheal and parenchymal strips but in both cases the inhibitory potency was less than that on ovalbumin response. NZ-107 was a more potent inhibitor of ovalbumin-induced SRS-A release than histamine release in lung fragments but was ineffective in inhibiting A23187-induced SRS-A and histamine release. NZ-107 at a concentration of 10 microM more effectively inhibited LTC4- and histamine-induced tracheal contractions than it did LTC4 in the presence of 45 mM serine-borate. These results suggest that NZ-107 selectively inhibits antigen-induced SRS-A responses in airway tissues of the guinea-pig.
Yamamoto
A
A
Shiraoka Research Station of Biological Science, Nissan Chemical Industries Ltd, Saitama, Japan.
Shikada
K
K
Iwama
T
T
Sakashita
M
M
Hibi
M
M
Tanaka
S
S
D000818:Animals; D000001:Calcimycin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006168:Guinea Pigs; D006636:Histamine Release / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D010047:Ovalbumin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology*; D013189:SRS-A / Q000378:metabolism; D014132:Trachea / Q000187:drug effects
D011724:Pyridazines; D013189:SRS-A; C062698:NZ 107; D000001:Calcimycin; D010047:Ovalbumin