Sugawara T, Ohta T, Asano T, Ito S, Nakazato Y
Laboratory of Pharmacology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Eur J Pharmacol. 1997 Jan 14;319(1):123-30. doi: 10.1016/s0014-2999(96)00835-7.
Tacrine enhanced acetylcholine-induced catecholamine secretion with a concentration of up to 10 microM, but inhibited it at over 10 microM in perfused adrenal glands. Qualitatively the same result was obtained with physostigmine. Both tacrine and physostigmine only inhibited the secretory responses to carbachol and/or nicotine in perfused glands and dispersed chromaffin cells. Acetylcholinesterase activity of adrenal homogenates was inhibited by tacrine and physostigmine in a concentration-dependent manner. In whole-cell patch-clamp experiments, tacrine and physostigmine caused reversible inhibition of nicotine-evoked inward currents with a dose range similar to that for the inhibitory action on the secretory response. These results suggest that the enhancing effect of tacrine and physostigmine on acetylcholine-induced catecholamine secretion results from the prevention of enzymatic hydrolysis of acetylcholine in adrenal glands and that the inhibitory effect is due to the inhibition of nicotinic receptor-mediated membrane currents in adrenal chromaffin cells.
在灌注的肾上腺中，他克林在浓度高达10微摩尔时增强乙酰胆碱诱导的儿茶酚胺分泌，但在超过10微摩尔时则抑制该分泌。毒扁豆碱也得到了定性相同的结果。他克林和毒扁豆碱仅在灌注的腺体和分散的嗜铬细胞中抑制对卡巴胆碱和/或烟碱的分泌反应。他克林和毒扁豆碱以浓度依赖的方式抑制肾上腺匀浆的乙酰胆碱酯酶活性。在全细胞膜片钳实验中，他克林和毒扁豆碱对烟碱诱发的内向电流产生可逆性抑制，其剂量范围与对分泌反应的抑制作用相似。这些结果表明，他克林和毒扁豆碱对乙酰胆碱诱导的儿茶酚胺分泌的增强作用源于肾上腺中乙酰胆碱酶促水解的预防，而抑制作用则是由于肾上腺嗜铬细胞膜中烟碱受体介导的膜电流受到抑制。
