Berry J L, Elliott K R, Foster R W, Green K A, Murray M A, Small R C
Department of Physiological Sciences, University of Manchester.
Pulm Pharmacol. 1991;4(2):91-8. doi: 10.1016/0952-0600(91)90058-b.
Experiments have been performed using guinea-pig and bovine trachealis in order to determine whether cromakalim and RP 49356 share the same relaxant action and to analyse the mechanisms underlying this action. RP 49356 was approximately 3 times less potent than cromakalim in suppressing the spontaneous tone of guinea-pig trachea and, like cromakalim, was antagonised by glibenclamide and by phentolamine. Biochemical studies showed that relaxant concentrations of cromakalim and RP 49356 did not alter the cAMP or cGMP content of guinea-pig trachealis muscle and did not inhibit cAMP or cGMP hydrolysis by tracheal homogenates. Like cromakalim, RP 49356 caused marked hyperpolarisation of guinea-pig trachealis cells. Patch clamp recording using inside-out membrane patches from bovine trachealis showed that cromakalim, RP 49356, glibenclamide and phentolamine were each without effect on the open state probability (Popen) of large conductance, Ca(2+)-activated K(+)-channels. We conclude that cromakalim and RP 49356 share a similar action in opening K(+)-channels in the trachealis cell membrane. This action probably does not involve the intracellular accumulation of cyclic nucleotides and the channel involved is not the large conductance, Ca(2+)-dependent K(+)-channel.
为了确定克罗卡林和RP 49356是否具有相同的舒张作用并分析该作用的潜在机制，已使用豚鼠和牛气管进行了实验。在抑制豚鼠气管的自发张力方面，RP 49356的效力约为克罗卡林的三分之一，并且与克罗卡林一样，可被格列本脲和酚妥拉明拮抗。生化研究表明，克罗卡林和RP 49356的舒张浓度不会改变豚鼠气管平滑肌的环磷酸腺苷（cAMP）或环磷酸鸟苷（cGMP）含量，也不会抑制气管匀浆对cAMP或cGMP的水解。与克罗卡林一样，RP 49356可引起豚鼠气管细胞明显的超极化。使用牛气管的内向外膜片进行膜片钳记录表明，克罗卡林、RP 49356、格列本脲和酚妥拉明对大电导钙激活钾通道的开放概率（Popen）均无影响。我们得出结论，克罗卡林和RP 49356在打开气管细胞膜钾通道方面具有相似的作用。该作用可能不涉及环核苷酸的细胞内积累，且所涉及的通道不是大电导钙依赖性钾通道。
