Neuropeptide RFRP inhibits the pacemaker activity of terminal nerve GnRH neurons
Neuropeptide RFRP inhibits the pacemaker activity of terminal nerve GnRH neurons
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神经肽 RFRP 抑制终末神经 GnRH 神经元的起搏器活性
DOI：
10.1152/jn.00712.2012
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发表时间：
2013
影响因子：
2.5
通讯作者：
Y Oka
中科院分区：
文献类型：
--
作者：
C Umatani;H Abe;Y Oka
末梢神经促性腺激素释放激素(TN-GnRH)神经元具有自发的起搏活动，其放电频率可能调节GnRH多肽的释放，控制生殖行为的动机。以往对Tn-GnRH神经元电生理特性的研究报道了自体/旁分泌和突触调制对起搏器活动的兴奋性调制，但迄今未见抑制起搏器活动的报道。我们最近的研究表明，神经肽FF是一种在TN-GnRH神经元自身表达的Arg-Phe-amide(RFamide)肽，它以自分泌和旁分泌的方式抑制TN-GnRH神经元的起搏活动。在本研究中，我们研究了下丘脑产生的RFamide相关肽(RFRPs)是否作为抑制性突触调节剂调节TN-GnRH神经元的起搏活性。在三种硬骨鱼RFRP中，浸浴RFRP2可降低Tn-GnRH神经元的放电频率。这种抑制作用可被候选RFRP受体GPR147/74的强效拮抗剂RF9所减弱。RFRP2改变了Na+和K+的电导。RFRP2诱发电流的反转电位可被瞬时受体电位标准(TRPC)通道的抑制剂(La3+和2-氨基乙氧基二苯硼酸盐)和选择性较低的电压非依赖性K+通道阻断剂(Ba2+)所改变。通过比较RFRP2在人工脑脊液和各药物作用下的电流-电压关系，认为RFRP2诱导的电流由TRPC类通道电流和电压非依赖性K+电流组成。因此，从下丘脑神经元突触释放RFRP2可能通过关闭TRPC通道和开放电压非依赖性K+通道来抑制TN-GnRH神经元的起搏活动。这一新途径可能对生殖行为产生负面调节作用。
The terminal nerve gonadotropin-releasing hormone (TN-GnRH) neurons show spontaneous pacemaker activity whose firing frequency is suggested to regulate the release of GnRH peptides and control motivation for reproductive behaviors. Previous studies of the electrophysiological properties of TN-GnRH neurons reported excitatory modulation of pacemaker activity by auto/paracrine and synaptic modulations, but inhibition of pacemaker activity has not been reported to date. Our recent study suggests that neuropeptide FF, a type of Arg-Phe-amide (RFamide) peptide expressed in TN-GnRH neurons themselves, inhibits the pacemaker activity of TN-GnRH neurons in an auto- and paracrine manner. In the present study, we examined whether RFamide-related peptides (RFRPs), which are produced in the hypothalamus, modulate the pacemaker activity of TN-GnRH neurons as candidate inhibitory synaptic modulators. Bath application of RFRP2, among the three teleost RFRPs, decreased the frequency of firing of TN-GnRH neurons. This inhibition was diminished by RF9, a potent antagonist of GPR147/74, which are candidate RFRP receptors. RFRP2 changed the conductances for Na+and K+. The reversal potential for RFRP2-induced current was altered by inhibitors of the transient receptor potential canonical (TRPC) channel (La3+and 2-aminoethoxydiphenyl borate) and by a less selective blocker of voltage-independent K+channels (Ba2+). By comparing the current-voltage relationship in artificial cerebrospinal fluid with that under each drug, the RFRP2-induced current was suggested to consist of TRPC channel-like current and voltage-independent K+current. Therefore, synaptic release of RFRP2 from hypothalamic neurons is suggested to inhibit the pacemaker activity of TN-GnRH neurons by closing TRPC channels and opening voltage-independent K+channels. This novel pathway may negatively regulate reproductive behaviors.