González-Rubio Juana M, Rojo Jonathan, Tapia Laura, Maneu Victoria, Mulet José, Valor Luis M, Criado Manuel, Sala Francisco, García Antonio G, Gandía Luis
Instituto Teófilo Hernando, Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, C/Arzobispo Morcillo, 4, 28029 Madrid, Spain.
Eur J Pharmacol. 2006 Mar 27;535(1-3):53-60. doi: 10.1016/j.ejphar.2006.02.014. Epub 2006 Mar 20.
Choline, the precursor and the metabolite of acetylcholine, is reputed as a selective alpha7 nicotinic receptor agonist. In this study, however, we have seen that choline exerted a dual effect on bovine nicotinic receptors expressed in Xenopus oocytes. On the one hand, choline behaved as a weak full agonist on bovine alpha7-mediated inward currents, with an EC50 of 0.43 mM. On the other, choline blocked bovine alpha3beta4 currents, with an IC50 of 0.97 mM. The blockade by choline was fast (tau(on), 0.36 s), fully reversible (tau(off), 1.23 s), exhibited voltage-dependence (60% blockade at -100 mV and 30% blockade at -40 mV), and was of a non-competitive nature, suggesting an open-channel type of alpha3beta4 receptor blockade. Thus, choline by activating alpha7 receptors and/or blocking alpha3beta4 receptors might play a physiological role in the control of neurotransmission at cholinergic synapses where alpha7 and alpha3beta4 receptor are expressed.
胆碱作为乙酰胆碱的前体和代谢产物，被誉为一种选择性α7烟碱样受体激动剂。然而，在本研究中，我们发现胆碱对非洲爪蟾卵母细胞中表达的牛烟碱样受体具有双重作用。一方面，胆碱在牛α7介导的内向电流上表现为弱的完全激动剂，其半数有效浓度（EC50）为0.43 mM。另一方面，胆碱可阻断牛α3β4电流，其半数抑制浓度（IC50）为0.97 mM。胆碱的阻断作用迅速（开启时间常数τ(on)为0.36 s），完全可逆（关闭时间常数τ(off)为1.23 s），呈现电压依赖性（在-100 mV时阻断60%，在-40 mV时阻断30%），且具有非竞争性，提示为α3β4受体的开放通道型阻断。因此，胆碱通过激活α7受体和/或阻断α3β4受体，可能在表达α7和α3β4受体的胆碱能突触处的神经传递控制中发挥生理作用。
