Nicotinic cholinergic activation of magnocellular neurons of the hypothalamic paraventricular nucleus
Nicotinic cholinergic activation of magnocellular neurons of the hypothalamic paraventricular nucleus
复制标题
DOI：
10.1016/s0306-4522(01)00536-x
复制
发表时间：
2002-03
期刊：
影响因子：
3.3
通讯作者：
M. Zaninetti;E. Tribollet;D. Bertrand;M. Raggenbass
中科院分区：
文献类型：
--
作者：
M. Zaninetti;E. Tribollet;D. Bertrand;M. Raggenbass
本工作的目的是确定室旁神经元是否具有功能性的乙酰胆碱烟碱受体。使用红外视频显微镜和差分干涉对比光学技术，我们在下丘脑室旁核脑片上进行了全细胞记录。在M受体拮抗剂阿托品存在的情况下，加压微量注射局部应用乙酰胆碱，可引起室旁大细胞内分泌神经元内向电流的迅速上升。这种电流在突触传递阻滞剂的存在下持续存在。甲基乌头碱是含α7的烟碱受体的选择性拮抗剂，可被纳摩尔浓度的甲基乌头碱可逆地抑制，但对微摩尔浓度的二氢β赤霉胺不敏感，后者优先作用于非α7烟碱受体。此外，乙酰胆碱的作用可被新近合成的α7受体特异性烟碱激动剂exo-2-(2-吡啶)-7-氮杂双环[2.2.1]庚烷所模拟。乙酰胆碱也使室旁烟碱受体脱敏。脱敏明显，脱敏恢复迅速，这与室旁尼古丁受体含有α7亚单位的观点一致。室旁小细胞神经元不能诱发烟碱电流，提示这些神经元缺乏功能性的烟碱受体。电生理数据被光镜放射自显影证实，表明[125I]α-银环蛇毒素结合位点存在于室旁核的所有大细胞分裂中，但在该核的其他区域未被检测到。用针对加压素和催产素的抗体进行的免疫组织化学显示，对尼古丁激动剂的反应是加压素和催产素大细胞内分泌神经元的一种特性，在脑室旁核和视上核中都是如此。我们得出结论，尼古丁激动剂可以通过直接增加大细胞神经元的兴奋性来影响大细胞神经分泌系统。相比之下，它们可能对室旁小细胞神经元没有直接影响。
The aim of the present work was to determine whether paraventricular neurons possess functional acetylcholine nicotinic receptors. Using infrared videomicroscopy and differential interference contrast optics, we performed whole-cell recordings in hypothalamic slices containing the paraventricular nucleus. Acetylcholine, locally applied by pressure microejection in the presence of the muscarinic antagonist atropine, evoked a rapidly rising inward current in paraventricular magnocellular endocrine neurons. This current persisted in the presence of blockers of synaptic transmission. It could be reversibly suppressed by nanomolar concentrations of methyllycaconitine, a selective antagonist of α7-containing nicotinic receptors, but was insensitive to micromolar concentrations of dihydro-β-erythroidine, an antagonist acting preferentially on non-α7 nicotinic receptors. In addition, the effect of acetylcholine could be mimicked by exo-2-(2-pyridyl)-7-azabicyclo[2.2.1]heptane, a recently synthesized nicotinic agonist specific for α7 receptors. Acetylcholine also desensitized paraventricular nicotinic receptors. Desensitization was pronounced and recovery from desensitization was rapid, consistent with the notion that paraventricular nicotinic receptors contain the α7 subunit. Nicotinic currents could not be evoked in paraventricular parvocellular neurons, suggesting that these neurons are devoid of functional nicotinic receptors. The electrophysiological data were corroborated by light microscopic autoradiography, showing that [125I]α-bungarotoxin binding sites are present in all the magnocellular divisions of the paraventricular nucleus but are undetectable in other areas of this nucleus. Immunohistochemistry, performed using antibodies directed against vasopressin and oxytocin, indicated that responsiveness to nicotinic agonists was a property of vasopressin as well as of oxytocin magnocellular endocrine neurons, in both the paraventricular and the supraoptic nucleus. We conclude that nicotinic agonists can influence the magnocellular neurosecretory system by directly increasing the excitability of magnocellular neurons. By contrast, they are probably without direct effects on paraventricular parvocellular neurons.