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- W1899720021 abstract "The effects were observed of a newly synthesized bronchodilator, KC 339 [N-(2-cyanoethyl)-2,2-bis-fluoromethyl-6-nitro-2H-1-benzopyran-4- carbothioamide], on the electrical and mechanical properties of dog tracheal smooth muscle tissues and on accumulation of second messengers. KC 399 hyperpolarized the membrane in a concentration-dependent manner, the minimum concentration required to produce hyperpolarization being 1 nM and the maximum hyperpolarization occurring with 10 nM. The hyperpolarization was still observed in low K+ solution (< 1.2 mM), but not in high K+ solution (> 20 nM). Similarly, KC 399 inhibited the contraction evoked by less than 30 mM K+, but not by higher concentrations of K+ (> 30 mM). KC 399 (10 nM) suppressed the depolarization and membrane potential oscillation induced by carbachol (< 300 nM). In muscle tissues precontracted with 100 nM carbachol, KC 399 caused a concentration-dependent relaxation. The IC50 value for KC 399 was 4.2 nM (pIC50: 8.38 +/- 0.09, n = 7) and the maximum inhibition induced by 100 nM KC 399 was 96.1 +/- 0.7% (n = 7). KC 399 inhibited more effectively the tonic response of the contraction than the initial phasic response induced by carbachol. The relaxation and hyperpolarization induced by KC 399 were antagonized by glibenclamide and in part by charybdotoxin due to depolarization of the membrane. Carbachol increased the amount of d-myo-inositol-1,4,5-trisphosphate (InsP3), the maximal value occurring 10 sec after application.(ABSTRACT TRUNCATED AT 250 WORDS)" @default.
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- W1899720021 date "1994-01-01" @default.
- W1899720021 modified "2023-09-23" @default.
- W1899720021 title "Effects of KC 399, a novel ATP-sensitive K+ channel opener, on electrical and mechanical responses in dog tracheal smooth muscle." @default.
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