Blockade of Ca2+ -activated K+ channels by galantamine can also contribute to the potentiation of catecholamine secretion from chromaffin cells.
Blockade of Ca2+ -activated K+ channels by galantamine can also contribute to the potentiation of catecholamine secretion from chromaffin cells.
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加兰他敏阻断 Ca2 激活的 K 通道也有助于增强嗜铬细胞分泌儿茶酚胺。
DOI：
10.1016/j.ejphar.2006.07.032
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发表时间：
2006
影响因子：
5
通讯作者：
Manuela G. López
中科院分区：
文献类型：
--
作者：
E. Alés;F. Gullo;E. Arias;R. Olivares;Antonio G. García;E. Wanke;Manuela G. López
加兰他敏是临床上用于治疗阿尔茨海默病的药物，但其作用机制仍有争议。在这里，我们解决了这个问题，加兰他敏是否可以通过抑制小电导钙激活的K+通道（KCa 2）增强神经递质的释放。加兰他敏增强了10 s脉冲乙酰胆碱和高[K+]oapplied到快速灌流的牛肾上腺嗜铬细胞群诱导的儿茶酚胺分泌反应。在0.1-1 μM浓度范围内，加兰他敏可显著促进儿茶酚胺的释放，但未发现浓度依赖性。KCa 2通道阻断剂apamin（0.3 μM）阻断了加兰他敏对乙酰胆碱诱发分泌的增强作用。与apamin一样，加兰他敏也改变了动作电位的放电，但程度较小。此外，1 μM加兰他敏使KCa 2电流降低41%，而不改变电压依赖性Ca 2+电流。这些结果构成了第一个直接证据，证明加兰他敏可以通过阻断KCa 2通道来增强神经递质的释放，除了其已经证明的轻度阻断乙酰胆碱酯酶或增强变构烟碱受体的能力之外。
Galantamine is a drug in clinical use for the treatment of Alzheimer's disease, but its mechanism(s) of action remains controversial. Here we addressed the question whether galantamine could potentiate neurotransmitter release by inhibiting small conductance Ca2+-activated K+channels (KCa2). Galantamine potentiated catecholamine secretory responses induced by 10 s pulses of acetylcholine and high [K+]oapplied to fast-superfused bovine adrenal chromaffin cell populations. Catecholamine release was significantly enhanced by galantamine although we did not find concentration dependence in the range 0.1–1 μM. The KCa2 channel blocker apamin (0.3 μM) occluded the potentiating effects of galantamine on acetylcholine-evoked secretion. Like apamin, galantamine also modified the firing of action potentials, but to a lesser extent. In addition, 1 μM galantamine reduced by 41% the KCa2 current without modifying the voltage-dependent Ca2+currents. These results constitute the first direct evidence that galantamine can potentiate neurotransmitter release by blocking KCa2 channels, in addition to its already demonstrated capacity to mildly block acetylcholinesterase or potentiate allosterically nicotinic receptors.
一类新型变构作用配体增强了神经元烟碱乙酰胆碱受体的激动剂反应。
DOI：
--
发表时间：
1996
期刊：
Molecular pharmacology.
影响因子：
--
作者：
Schrattenholz,A;Pereira,EF;Roth,U;Weber,KH;Albuquerque,EX;Maelicke,A
通讯作者：
Maelicke,A
影响因子：
2.5
作者：
Prakriya, M;Lingle, CJ
通讯作者：
Lingle, CJ
影响因子：
3.6
作者：
Santos, MD;Alkondon, M;Albuquerque, EX
通讯作者：
Albuquerque, EX