Barajas-López C, Peres A L, Espinosa-Luna R, Reyes-Vázquez C, Prieto-Gómez B
Intestinal Disease Research Program, McMaster University, Hamilton, Ontario, Canada.
Eur J Pharmacol. 1996 Oct 3;312(3):319-25. doi: 10.1016/0014-2999(96)00481-5.
Melatonin, a hormone produced and released by the pineal gland is also synthesized by cells of the gastrointestinal wall, where it might be a local regulator of gut functions. In this study, we investigated the possible role of melatonin as a modulator of the enteric nervous system. Intracellular recordings were made in neurons of the submucosal plexus from the guinea-pig ileum to measure the melatonin effects on their electrophysiological properties. Melatonin did not alter the membrane potential, the membrane resistance and the noradrenergic inhibitory postsynaptic potentials. However, melatonin (30-3000 microM) reversibly decreased the amplitude of nicotinic excitatory postynaptic potentials (EPSPs) in a concentration-dependent manner (IC50 = 247 microM). These actions of melatonin were not modified by the presence of idazoxan and atropine indicating that they are not mediated by endogenous release of acetylcholine, noradrenaline, or by direct activation of alpha 2-adrenoceptors or muscarinic receptors. The superfusion of melatonin also blocked the nicotinic depolarizations induced by locally applied acetylcholine, indicating that at least part of its effects are postsynaptic. In voltage-clamp experiments, using the whole-cell configuration, melatonin also inhibited the nicotinic inward currents induced by acetylcholine (IACh) in a concentration-dependent manner (IC50 = 257 microM). Melatonin decreased the maximal IACh but did not affect the potency of acetylcholine to induce this current, indicating a noncompetitive antagonism. This effect was voltage-dependent. Our observations indicate that melatonin inhibits the fast EPSPs by directly and specifically blocking the nicotinic channels. The relative high concentrations of melatonin required to produce such an effect rules this out as one of its humoral actions. Such an effect, however, might be of physiological significance close to the cells that release melatonin in the gastrointestinal wall or in other organs.
褪黑素是一种由松果体产生和释放的激素，胃肠道壁细胞也能合成，它可能是肠道功能的局部调节因子。在本研究中，我们调查了褪黑素作为肠神经系统调节剂的可能作用。对豚鼠回肠黏膜下神经丛的神经元进行细胞内记录，以测量褪黑素对其电生理特性的影响。褪黑素不会改变膜电位、膜电阻和去甲肾上腺素能抑制性突触后电位。然而，褪黑素（30 - 3000微摩尔）以浓度依赖的方式可逆地降低烟碱兴奋性突触后电位（EPSP）的幅度（IC50 = 247微摩尔）。咪唑克生和阿托品的存在并未改变褪黑素的这些作用，这表明它们不是由乙酰胆碱、去甲肾上腺素的内源性释放介导的，也不是由α2 - 肾上腺素能受体或毒蕈碱受体的直接激活介导的。褪黑素的灌注也阻断了局部应用乙酰胆碱诱导的烟碱去极化，这表明其至少部分作用是突触后作用。在电压钳实验中，采用全细胞模式，褪黑素也以浓度依赖的方式抑制乙酰胆碱诱导的烟碱内向电流（IACh）（IC50 = 257微摩尔）。褪黑素降低了最大IACh，但不影响乙酰胆碱诱导该电流的效能，表明是非竞争性拮抗作用。这种作用是电压依赖性的。我们的观察结果表明，褪黑素通过直接和特异性地阻断烟碱通道来抑制快速EPSP。产生这种作用所需的相对高浓度的褪黑素排除了它作为一种体液作用的可能性。然而，这种作用在胃肠道壁或其他器官中释放褪黑素的细胞附近可能具有生理意义。
