Nielsen-Kudsk J E, Thirstrup S
Institute of Pharmacology, University of Aarhus, Denmark.
Pulm Pharmacol. 1993 Sep;6(3):185-92. doi: 10.1006/pulp.1993.1025.
Glibenclamide, glipizide and glibornuride showed dual effects in guinea-pig isolated trachea. The drugs antagonized the relaxant response to the K+ channel opener cromakalim (order of effectiveness: glibenclamide > glipizide > glibornuride) and at concentrations of 1-1000 microM produced airway smooth muscle relaxation (order of potency: glibenclamide > glipizide = glibornuride). Gliclazide, tolbutamide and chlorpropamide did not antagonize cromakalim nor did the two latter drugs produce tracheal relaxation. The sulphonylureas and cromakalim were compared as airway relaxants against a panel of different spasmogens. The order of tissue responsiveness for the sulphonylureas was: spontaneous tone = LTD4 > PGF2 alpha = histamine = 30 mM K+ > carbachol and for cromakalim: spontaneous tone = LTD4 = PGF2 alpha = histamine > carbachol > 30 mM K+. Glibenclamide, but not cromakalim, relaxed contractions induced by 124 mM K+. Phentolamine and Ba2+, which are reported blockers of ATP-regulated K+ channels, failed to influence sulphonylurea-induced airway smooth muscle relaxation. Glibenclamide reversed tracheal relaxation produced by cromakalim, whereas cromakalim failed to reverse relaxation induced by glibenclamide. The mechanism for the additional property of sulphonylureas to relax airway smooth muscle is unclear, but the results do not support a role for involvement of cromakalim-sensitive K+ channels.
格列本脲、格列吡嗪和格列波脲在豚鼠离体气管中显示出双重作用。这些药物拮抗了对钾通道开放剂克罗卡林的舒张反应（效力顺序：格列本脲＞格列吡嗪＞格列波脲），并且在1 - 1000微摩尔浓度下可引起气道平滑肌舒张（效能顺序：格列本脲＞格列吡嗪 = 格列波脲）。格列齐特、甲苯磺丁脲和氯磺丙脲既不拮抗克罗卡林，后两种药物也不引起气管舒张。将磺酰脲类药物和克罗卡林作为气道舒张剂与一组不同的致痉剂进行了比较。磺酰脲类药物的组织反应性顺序为：自发张力 = 白三烯D4＞前列腺素F2α = 组胺 = 30毫摩尔钾离子＞卡巴胆碱，而克罗卡林的顺序为：自发张力 = 白三烯D4 = 前列腺素F2α = 组胺＞卡巴胆碱＞30毫摩尔钾离子。格列本脲而非克罗卡林可舒张由124毫摩尔钾离子诱导的收缩。酚妥拉明和钡离子是报道的ATP调节钾通道阻滞剂，它们未能影响磺酰脲类药物诱导的气道平滑肌舒张。格列本脲可逆转克罗卡林引起的气管舒张，而克罗卡林未能逆转格列本脲诱导的舒张。磺酰脲类药物舒张气道平滑肌这一额外特性的机制尚不清楚，但结果不支持克罗卡林敏感钾通道参与其中的作用。
