Regional and species differences in glyburide-sensitive K+ channels in airway smooth muscles as estimated from actions of KC 128 and levcromakalim.
1. The purpose of the present experiments was to elucidate the differences in actions of two K+ channel openers, KC 128 and levcromakalim, on the carbachol-induced contraction, membrane potential and 86Rb+ efflux of the dog tracheal and bronchial smooth muscles. Furthermore, we compared the effects of these agents on guinea-pig and human airway smooth muscles. 2. In the dog tracheal and bronchial smooth muscle tissues, levcromakalim induced a concentration-dependent relaxation of the carbachol-induced contraction. The IC50 values were 0.35 microM (pIC50: 6.46 +/- 0.10, n = 9) and 0.55 microM (pIC50: 6.26 +/- 0.07, n = 5), respectively. KC 128 relaxed bronchial smooth muscles precontracted by carbachol with an IC50 value of 0.19 microM (pIC50: 6.73 +/- 0.10, n = 7). However, KC 128 had almost no effect on the contraction evoked by carbachol in the trachea (IC50 > 10 microM). The relaxations induced by levcromakalim and KC 128 were antagonized by glyburide (0.03-1 microM) but not by charybdotoxin (100 nM). 3. Levcromakalim (1 microM) hyperpolarized the membrane of both dog tracheal and bronchial smooth muscle cells, whereas KC 128 (1 microM) hyperpolarized the membrane of bronchial but not of tracheal smooth muscle cells. 4. Levcromakalim (10 microM) increased 86Rb+ efflux rate from both tracheal and bronchial smooth muscle tissues but KC 128 (10 microM) increased 86Rb+ efflux rate only from bronchial and not tracheal smooth muscle tissues. Glyburide (1 microM) prevented the hyperpolarization and the 86Rb+ efflux induced by these agents at the same concentration as observed for mechanical responses. 5. Both KC 128 and levcromakalim relaxed the guinea-pig isolated tracheal smooth muscles precontracted by carbachol (100 nM), histamine (3 micro M) or U46619 (10 nM). KC 128 was approximately 10 times more potent than levcromakalim for each agonist.6. In human bronchial smooth muscles, levcromakalim but not KC 128 induced a concentration dependent relaxation of the carbachol-induced contraction.7. It is concluded that KC 128 has relaxant and hyperpolarizing effects in the dog bronchial and guinea-pig tracheal smooth muscles, but not in the dog tracheal and human bronchial smooth muscles.On the other hand, levcromakalim acts consistently on all the above airway smooth muscle tissues.These results indicate that there are regional and species differences in distribution of K+ channels, and at least two different K+ channel opener- and glyburide-sensitive K+ channels are present in the dog airway smooth muscles.
Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co. Ltd., Shizuoka, Japan.
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Kamei
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Yoshida
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Imagawa
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Nabata
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Kuriyama
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D001980:Bronchi / Q000187:drug effects* / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology; D019806:Cromakalim; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D005905:Glyburide / Q000494:pharmacology*; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology*; D013045:Species Specificity; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
D001578:Benzopyrans; C092107:KC 128; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D002217:Carbachol; D005905:Glyburide