Physiology and Pharmacology, Oregon Health and Science University, Portland, OR 97239, USA.
Adv Exp Med Biol. 2013;784:113-31. doi: 10.1007/978-1-4614-6199-9_6.
Kisspeptin binding to its cognate G protein-coupled receptor (GPR54, aka Kiss1R) in gonadotropin-releasing hormone (GnRH) neurons stimulates peptide release and activation of the reproductive axis in mammals. Kisspeptin has pronounced pre- and postsynaptic effects, with the latter dominating the excitability of GnRH neurons. Presynaptically, kisspeptin increases the excitatory drive (both GABA-A and glutamate) to GnRH neurons and postsynaptically, kisspeptin inhibits an A-type and inwardly rectifying K(+) (Kir 6.2 and GIRK) currents and activates nonselective cation (TRPC) currents to cause long-lasting depolarization and increased action potential firing. The signaling cascades and the multiple intracellular targets of kisspeptin actions in native GnRH neurons are continuing to be elucidated. This review summarizes our current state of knowledge about kisspeptin signaling in GnRH neurons.
在促性腺激素释放激素(GnRH)神经元中,kisspeptin 与其同源 G 蛋白偶联受体(GPR54,又名 Kiss1R)结合,刺激肽的释放并激活哺乳动物的生殖轴。Kisspeptin 具有明显的突触前和突触后效应,后者主导 GnRH 神经元的兴奋性。突触前,kisspeptin 增加 GnRH 神经元的兴奋性驱动(GABA-A 和谷氨酸),突触后,kisspeptin 抑制 A 型和内向整流钾(Kir6.2 和 GIRK)电流,并激活非选择性阳离子(TRPC)电流,导致持久去极化和增加动作电位放电。kisspeptin 在原代 GnRH 神经元中的作用的信号级联和多个细胞内靶点仍在阐明中。这篇综述总结了我们目前对 GnRH 神经元中 kisspeptin 信号的了解。