Griffin A
Department of Physiology, St George's Hospital Medical School, London, UK.
Eur J Pharmacol. 1995 Jul 14;280(3):317-25. doi: 10.1016/0014-2999(95)00215-7.
The effects of three K+ channel openers on lysozyme output from submucosal gland serous cells and epithelial albumin transport following maintained submaximal stimulation by the secretagogues methacholine and phenylephrine were examined in the ferret trachea in vitro preparation. The K+ channel openers Ro 31-6930, 2-(6-cyano-2,2-dimethyl-2H-1-benzopyran-4-yl)-pyridine 1-oxide (10 nM-10 microM), levcromakalim, BRL38227 (10 nM-10 microM) and pinacidil (100 nM-10 microM) produced a concentration dependent inhibition of (20 microM) methacholine-induced lysozyme output, with pD2 values of 7.64, 7.72 and 7.28 respectively. Ro 31-6930 (10 nM-10 microM), levcromakalim (10 nM-10 microM) and pinacidil (1 nM-10 microM) also produced a concentration dependent inhibition of (100 microM) phenylephrine-induced lysozyme output, with pD2 values of 7.64, 6.55 and 9.16 respectively. Furthermore, glibenclamide (1 microM) produced a modest attenuation of the K+ channel opener effects on secretagogue-induced lysozyme output. All three K+ channel openers failed to produce any significant change in either methacholine or phenylephrine-induced albumin outputs. The K+ channel openers exerted marked effects on airway secretion processes, suggesting that these compounds may have an antisecretory effect. The relevance of the use of the K+ channel openers in airway disease remains to be determined.
在雪貂气管体外制备物中，研究了三种钾通道开放剂对促分泌剂乙酰甲胆碱和去氧肾上腺素持续亚最大刺激后黏膜下腺浆液细胞溶菌酶分泌及上皮白蛋白转运的影响。钾通道开放剂Ro 31-6930、2-(6-氰基-2,2-二甲基-2H-1-苯并吡喃-4-基)-吡啶1-氧化物（10 nM - 10 μM）、左旋克罗卡林、BRL38227（10 nM - 10 μM）和吡那地尔（100 nM - 10 μM）对（20 μM）乙酰甲胆碱诱导的溶菌酶分泌产生浓度依赖性抑制，pD2值分别为7.64、7.72和7.28。Ro 31-6930（10 nM - 10 μM）、左旋克罗卡林（10 nM - 10 μM）和吡那地尔（1 nM - 10 μM）对（100 μM）去氧肾上腺素诱导的溶菌酶分泌也产生浓度依赖性抑制，pD2值分别为7.64、6.55和9.16。此外，格列本脲（1 μM）对钾通道开放剂对促分泌剂诱导的溶菌酶分泌的作用有适度减弱。三种钾通道开放剂对乙酰甲胆碱或去氧肾上腺素诱导的白蛋白分泌均未产生任何显著变化。钾通道开放剂对气道分泌过程有显著影响，表明这些化合物可能具有抗分泌作用。钾通道开放剂在气道疾病中的应用相关性仍有待确定。
