Neuroendocrine regulatory peptide-1 and -2 (NERPs) inhibit the excitability of magnocellular neurosecretory cells in the hypothalamus.
Neuroendocrine regulatory peptide-1 and -2 (NERPs) inhibit the excitability of magnocellular neurosecretory cells in the hypothalamus.
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神经内分泌调节肽-1 和-2 (NERP) 抑制下丘脑巨细胞神经分泌细胞的兴奋性。
DOI：
10.1016/j.brainres.2014.03.038
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发表时间：
2014
期刊：
影响因子：
2.9
通讯作者：
Nakazato M
中科院分区：
文献类型：
--
作者：
Toshinai K;Saito T;Yamaguchi H;Sasaki K;Tsuchimochi W;Minamino N;Ueta Y;Nakazato M
神经内分泌调节肽（neuroendocrine regulatory peptide，NERP）-1和NERP-2是一类由神经内分泌蛋白VGF衍生的新型羧基端酰胺化肽。NERPs与加压素共定位于下丘脑室旁核（PVN）和视上核（SON），并抑制由脑室内施用血管紧张素II（AngII）和高渗盐水或浴施用AngII引起的加压素分泌。下丘脑的大细胞神经分泌细胞（MCNs）从其树突和索马体释放加压素和催产素。这两种细胞类型具有共同的电生理特性，响应谷氨酸和血管生成素II。我们研究了NERPs对MCN抑制作用的机制。PVN的微透析表明，NERPs抑制由AngII诱导的谷氨酸释放。SON的全细胞膜片钳研究表明，NERPs抑制血管紧张素II诱发的兴奋性突触后电流（EPSC）的增强而不影响振幅，表明NERPs通过突触前机制抑制EPSC。在河豚毒素和γ-氨基丁酸（GABA）A受体拮抗剂荷包牡丹碱的存在下，NERP-2的抑制作用减弱，而NERP-1的抑制作用不减弱。这些结果表明，NERP-1抑制连接到MNC的突触前神经元，而NERP-2激活GABA能中间神经元，其抑制突触前神经元;因此，两种肽抑制加压素释放。这项研究表明，NERPs的功能作为加压素释放的抑制性调节剂。
Neuroendocrine regulatory peptide (NERP)-1 and NERP-2 (NERPs) are novel carboxy-terminally amidated peptides derived from the neurosecretory protein VGF. NERPs are colocalized with vasopressin in the paraventricular nucleus (PVN) and the supraoptic nucleus (SON) of the hypothalamus, and suppress vasopressin secretion evoked by intracerebroventricular administration of angiotensin II (AngII) and hypertonic saline or bath administration of AngII. Magnocellular neurosecretory cells (MCNs) of the hypothalamus release vasopressin and oxytocin from their dendrites and soma. The two cell types have common electrophysiological properties in response to glutamate and AngII. We investigated the mechanisms underlying the suppressive effects of NERPs on MCNs. Microdialysis of the PVN demonstrated that NERPs suppressed glutamate release induced by AngII. A whole-cell patch-clamp study of the SON showed that NERPs suppressed the potentiation of excitatory postsynaptic currents (EPSCs) evoked by AngII without affecting the amplitude, indicating that NERPs suppressed EPSCs by a presynaptic mechanism. The suppressive effect of NERP-2, but not NERP-1, was blunted in the presence of tetrodotoxin and bicuculline, a γ-aminobutyric acid (GABA) A receptor antagonist. These results indicate that NERP-1 suppresses presynaptic glutamatergic neurons connected to MNCs, whereas NERP-2 activates GABAergic interneurons, which suppress presynaptic glutamatergic neurons; thus, both peptides suppress vasopressin release. This study demonstrates that NERPs function as inhibitory modulators of vasopressin release.