Aas P, Gaudry-Talarmain Y M, Fonnum F
Norwegian Defence Research Establishment, Division for Environmental Toxicology, Kjeller.
Eur J Pharmacol. 1991 Jul 9;199(3):357-62. doi: 10.1016/0014-2999(91)90500-p.
The effect of the vesicular acetylcholine (ACh) transport blocker trans-2-(4- phenyl-piperidino)-cyclohexanol (AH5183) was studied in bronchial smooth muscle during activation of the vagus nerve. AH5183 inhibited in a dose-dependent manner the Ca(2+)-sensitive electrically induced smooth muscle contractions in vitro with a half-inhibitory concentration (IC50) of 1.6 +/- 0.4 microM. The inhibition was complete within 68 +/- 1 min (n = 8) at approximately 20 microM AH5183 and was partly reversible after washing of the preparations. AH5183 (20 microM) reduced the level of endogenous ACh by 47.4 +/- 7.6% (n = 4) during this time period. The effect of AH5183 is most likely prejunctional, since the contractions induced post-junctionally by carbachol were not altered by AH5183. The irreversible anticholinesterase, soman, increased the tonus of airway smooth muscle as a result of accumulation of spontaneously released ACh from prejunctional leakage. AH5183 had no effect on this increase of muscle contraction. The present results show that the nerve-evoked release of ACh comes from an AH5183-sensitive pool, probably a vesicular pool, whereas leakage of ACh presumably comes from the cytoplasmic pool in airway smooth muscle.
在迷走神经激活过程中，研究了囊泡乙酰胆碱（ACh）转运阻滞剂反式-2-（4-苯基-哌啶基）-环己醇（AH5183）对支气管平滑肌的作用。AH5183在体外以剂量依赖方式抑制钙敏感电诱导的平滑肌收缩，其半抑制浓度（IC50）为1.6±0.4微摩尔。在约20微摩尔AH5183作用下，68±1分钟内抑制作用完全（n = 8），制剂冲洗后部分可逆。在此时间段内，AH5183（20微摩尔）使内源性ACh水平降低47.4±7.6%（n = 4）。AH5183的作用很可能是作用于神经节前，因为卡巴胆碱在神经节后诱导的收缩未被AH5183改变。不可逆抗胆碱酯酶索曼因神经节前泄漏自发释放的ACh积累而增加气道平滑肌张力。AH5183对这种肌肉收缩增加无作用。目前结果表明，神经诱发的ACh释放来自AH5183敏感池，可能是囊泡池，而ACh泄漏大概来自气道平滑肌的细胞质池。
