Hamaguchi M, Ishibashi T, Imai S
Department of Pharmacology, Niigata University School of Medicine, Japan.
J Pharmacol Exp Ther. 1992 Jul;262(1):263-70.
To elucidate the involvement of K+ channels in the smooth muscle relaxation by glyceryl trinitrate (GTN) and sodium nitroprusside (SNP), effects of several K+ channel antagonists on the relaxant responses to GTN, SNP and 8-bromoguanosine 3',5'-cyclic monophosphate (8-Br-cGMP) were studied in bovine tracheal smooth muscle. Although an antagonist of large conductance Ca(++)-activated K+ channel, charybdotoxin, produced no definite effect on the relaxation induced by GTN, SNP and atriopeptin in the rabbit aortic ring preparation, this antagonist inhibited the relaxation by GTN, SNP, atriopeptin and 8-Br-cGMP in the bovine tracheal smooth muscle. Methylene blue, a soluble guanylate cyclase inhibitor, also had an inhibitory effect on the relaxation by GTN and SNP. Both apamin, a small conductance Ca(++)-activated K+ channel antagonist, and glibenclamide, an ATP-sensitive K+ channel antagonist, did not exhibit any inhibitory effect on the relaxant responses to GTN and SNP. GTN and SNP increased cGMP content. The increment was attenuated by methylene blue, whereas it was unaffected by charybdotoxin. These results indicate the involvement of large conductance Ca(++)-activated K+ channel in the relaxation of bovine tracheal smooth muscle by GTN, SNP and 8-Br-cGMP. The activation of K+ channel by GTN and SNP is thought to occur via increases in cGMP content.
为阐明钾离子通道在硝酸甘油（GTN）和硝普钠（SNP）所致平滑肌舒张中的作用，研究了几种钾离子通道拮抗剂对牛气管平滑肌对GTN、SNP和8-溴鸟苷3',5'-环一磷酸（8-Br-cGMP）舒张反应的影响。尽管大电导钙激活钾通道拮抗剂蝎毒素对兔主动脉环标本中GTN、SNP和心房肽所致舒张无明确作用，但该拮抗剂可抑制牛气管平滑肌中GTN、SNP、心房肽和8-Br-cGMP所致舒张。可溶性鸟苷酸环化酶抑制剂亚甲蓝对GTN和SNP所致舒张也有抑制作用。小电导钙激活钾通道拮抗剂蜂毒明肽和ATP敏感性钾通道拮抗剂格列本脲对GTN和SNP的舒张反应均无抑制作用。GTN和SNP可增加环鸟苷酸（cGMP）含量。亚甲蓝可减弱该增量，而蝎毒素对其无影响。这些结果表明大电导钙激活钾通道参与了GTN、SNP和8-Br-cGMP所致牛气管平滑肌舒张。GTN和SNP对钾离子通道的激活被认为是通过增加cGMP含量而发生的。
