Weston A H, Longmore J, Newgreen D T, Edwards G, Bray K M, Duty S
Department of Physiological Sciences, University of Manchester, UK.
Blood Vessels. 1990;27(2-5):306-13. doi: 10.1159/000158823.
Cromakalim, pinacidil, nicorandil, diazoxide and RP-49356 belong to the class of drugs termed potassium channel openers. In rat portal vein diazoxide, like cromakalim, abolished spontaneous mechanical and electrical activity and in rat aorta caused an increase in 86Rb efflux and inhibited KCl(20 mM)-induced contractions. However, in contrast to cromakalim, diazoxide (greater than 100 microM) also inhibited mechanical responses evoked by 80 mM KCl in rat aorta suggesting that it possesses pharmacological properties in addition to K channel opening. Since glibenclamide can attenuate the effects of cromakalim and diazoxide in vascular tissues, it is possible that a channel resembling the ATP-sensitive K channel found in pancreatic beta-cells may be involved in the vasorelaxant effects of these agents. However, differences exist in the order of potency of cromakalim and diazoxide for producing smooth muscle relaxation and for decreasing insulin secretion in pancreatic beta-cells. Furthermore galanin (which opens ATP-sensitive K channels in beta-cells) increases mechanical activity in rat portal vein. It is anticipated that new chemical developments will produce K channel opening molecules with greater potency and tissue selectivity.
克罗卡林、吡那地尔、尼可地尔、二氮嗪和RP - 49356属于被称为钾通道开放剂的一类药物。在大鼠门静脉中，二氮嗪与克罗卡林一样，可消除自发的机械和电活动，在大鼠主动脉中可使86Rb外流增加，并抑制氯化钾（20 mM）诱导的收缩。然而，与克罗卡林不同的是，二氮嗪（大于100 microM）还可抑制大鼠主动脉中80 mM氯化钾诱发的机械反应，这表明它除了具有开放钾通道的作用外，还具有其他药理特性。由于格列本脲可减弱克罗卡林和二氮嗪在血管组织中的作用，因此有可能在胰腺β细胞中发现的类似于ATP敏感性钾通道的通道参与了这些药物的血管舒张作用。然而，克罗卡林和二氮嗪在产生平滑肌舒张和降低胰腺β细胞胰岛素分泌方面的效价顺序存在差异。此外，甘丙肽（可打开β细胞中的ATP敏感性钾通道）可增加大鼠门静脉中的机械活动。预计新的化学进展将产生效力更高、组织选择性更强的钾通道开放分子。
