Raeburn D, Brown T J
Rhône-Poulenc Rorer Inc., Dagenham Research Center, Essex, England.
J Pharmacol Exp Ther. 1991 Feb;256(2):480-5.
RP 49356 is a novel compound which relaxes airway smooth muscle in vitro. Like cromakalim, RP 49356 reduced contractility in guinea pig isolated trachealis under basal conditions or when challenged with low (less than 20 mM) but not high K+. These effects were antagonized by the sulphonylureas glibenclamide and glipizide. This spectrum of action is typical of the class of compounds known as potassium channel openers (KCOs). Unlike RP 49356 and cromakalim, nifedipine had no effect on basal tone, relaxed tissues contracted with low or high K+ and was not antagonized by the sulphonylureas. These data suggest that the KCOs are not acting directly at the voltage-gated Ca++ channel in this tissue. RP 49356 and cromakalim were similar to nifedipine by being more potent at relaxing tissues precontracted with carbachol or histamine (spasmolytic effects) than they were at preventing initiation of the response to these spasmogens (antispasmogenic effects). Because the maintained phase of contraction in airway smooth muscle may be associated with some Ca++ influx, the data presented here suggests that, like nifedipine, the KCOs are more active smooth muscle relaxants under conditions of Ca++ influx. In summary, RP 49356, like cromakalim, is a compound which relaxes airway smooth muscle in vitro by opening a sulphonylurea-sensitive K+ channel which may be similar to the ATP-sensitive K+ channel found in other tissues.
RP 49356是一种新型化合物，它能在体外使气道平滑肌舒张。与克罗卡林一样，RP 49356在基础条件下或受到低浓度（低于20 mM）而非高浓度钾离子刺激时，可降低豚鼠离体气管的收缩性。这些作用可被磺脲类药物格列本脲和格列吡嗪拮抗。这种作用谱是被称为钾通道开放剂（KCOs）的一类化合物的典型特征。与RP 49356和克罗卡林不同，硝苯地平对基础张力无影响，可使由低浓度或高浓度钾离子收缩的组织舒张，且不受磺脲类药物拮抗。这些数据表明，在该组织中，KCOs并非直接作用于电压门控钙离子通道。RP 49356和克罗卡林与硝苯地平相似，在舒张由卡巴胆碱或组胺预收缩的组织（解痉作用）方面比预防对这些致痉剂的反应起始（抗致痉作用）更有效。因为气道平滑肌收缩的持续阶段可能与一些钙离子内流有关，此处呈现的数据表明，与硝苯地平一样，KCOs在钙离子内流的情况下是更有效的平滑肌舒张剂。总之，RP 49356与克罗卡林一样，是一种通过开放对磺脲类药物敏感的钾通道来在体外使气道平滑肌舒张的化合物，该钾通道可能类似于在其他组织中发现的ATP敏感性钾通道。
