Gater P R, Paciorek P M, McKean J C, Wilson K, Brewster M, Waterfall J F
Department of Biology, Roche Products Ltd., Welwyn Garden City, Hertfordshire, UK.
Eur J Pharmacol. 1993 Jul 6;238(1):59-64. doi: 10.1016/0014-2999(93)90505-c.
This study compares the effects of two K(+0-channel openers, Ro 31-6930 and BRL 38227, on cholinergically-evoked contraction of guinea-pig airways to examine whether either compound acts through prejunctional inhibition of the release of acetylcholine. In the isolated trachea, Ro 31-6930 and BRL 38227 evoked concentration-dependent inhibition of tone generated by electrical field stimulation with pD2 values of 7.03 (6.77-7.29) and 6.26 (5.91-6.61) respectively and of that elicited by acetylcholine with pD2 values of 7.38 (6.52-8.24) and 6.65 (6.16-7.13). Neither compound was more potent against responses to electrical field stimulation than against acetylcholine. In the anaesthetised guinea-pig, Ro 31-6930 inhibited the bronchoconstriction evoked by bilateral vagus nerve stimulation and intravenous acetylcholine with ID50 values of 12.9 +/- 3.9 and 3.6 +/- 1.3 micrograms/kg i.v. respectively. The corresponding values for BRL 38227 were 356 +/- 157 and 37.9 +/- 13.4 micrograms/kg i.v. respectively. Thus, in vivo, both compounds were more potent against acetylcholine than against vagal stimulation. These results provide indirect evidence that K(+)-channel openers do not inhibit the release of acetylcholine from parasympathetic nerves in guinea-pig airway smooth muscle.
本研究比较了两种钾通道开放剂Ro 31 - 6930和BRL 38227对豚鼠气道胆碱能诱发收缩的影响，以检查这两种化合物是否通过对乙酰胆碱释放的节前抑制起作用。在离体气管中，Ro 31 - 6930和BRL 38227引起电场刺激产生的张力的浓度依赖性抑制，pD2值分别为7.03（6.77 - 7.29）和6.26（5.91 - 6.61），以及乙酰胆碱引起的张力的浓度依赖性抑制，pD2值分别为7.38（6.52 - 8.24）和6.65（6.16 - 7.13）。两种化合物对电场刺激反应的效力均不比对乙酰胆碱的效力更强。在麻醉的豚鼠中，Ro 31 - 6930抑制双侧迷走神经刺激和静脉注射乙酰胆碱诱发的支气管收缩，ID50值分别为12.9±3.9和3.6±1.3微克/千克静脉注射。BRL 38227的相应值分别为356±157和37.9±13.4微克/千克静脉注射。因此，在体内，两种化合物对乙酰胆碱的效力均比对迷走神经刺激的效力更强。这些结果提供了间接证据，表明钾通道开放剂不会抑制豚鼠气道平滑肌中副交感神经释放乙酰胆碱。
