Jhamandas Jack H, MacTavish David, Harris Kim H
Department of Medicine (Neurology) and Centre for Neuroscience, University of Alberta, Edmonton, Alta., Canada T6G 2B7.
Peptides. 2006 May;27(5):973-9. doi: 10.1016/j.peptides.2005.07.030. Epub 2006 Mar 6.
Neuropeptide FF (NPFF) is an octapeptide belonging to an extended family of RF amide peptides that have been implicated in a wide variety of physiological functions in the brain. NPFF and its receptors are abundantly expressed in the rat brain and spinal cord including the hypothalamic paraventricular nucleus (PVN), an autonomic nucleus critical for the secretion of neurohormones and the regulation of sympathetic outflow. In this study, we sought to examine the effects of NPFF on GABAergic inhibitory synaptic input to magnocellular neurosecretory cells (MNCs) of the PVN, which secrete the neurohormones, vasopressin and oxytocin from their terminals in the neurohypophysis. Whole cell patch clamp recordings under voltage clamp conditions were performed from PVN MNCs in the brain slice. Bicuculline-sensitive inhibitory postsynaptic currents (IPSCs) were isolated in the presence of glutamate receptor blockers. In tetrodotoxin, NPFF (5 microM) caused an increase in frequency, but not amplitude of miniature inhibitory postsynaptic currents (mIPSCs) in MNCs indicating a presynaptic locus of action for this peptide. Intracerebroventricular application of NPFF resulted in an activation of GABAergic neurons located adjacent to the PVN as revealed by immunohistochemistry for Fos protein and in situ hybridization for glutamic acid decarboxylase (GAD67) mRNA. Based on these observations we conclude that NPFF facilitates inhibitory input to MNCs of the PVN via GABAergic interneurons located in immediate vicinity of the nucleus. These findings provide a cellular and anatomic basis for the NPFF-induced inhibition of vasopressin release has been reported consequent to hypovolemia and hyperosmolar stimulation.
神经肽FF（NPFF）是一种八肽，属于RF酰胺肽的一个扩展家族，这些肽与大脑中的多种生理功能有关。NPFF及其受体在大鼠脑和脊髓中大量表达，包括下丘脑室旁核（PVN），这是一个对神经激素分泌和交感神经输出调节至关重要的自主神经核。在本研究中，我们试图研究NPFF对PVN大细胞神经分泌细胞（MNC）的GABA能抑制性突触输入的影响，这些细胞从其在神经垂体的终末分泌神经激素血管加压素和催产素。在脑片上对PVN MNC进行电压钳条件下的全细胞膜片钳记录。在存在谷氨酸受体阻滞剂的情况下分离出荷包牡丹碱敏感的抑制性突触后电流（IPSCs）。在河豚毒素存在下，NPFF（5微摩尔）导致MNC中微小抑制性突触后电流（mIPSCs）的频率增加，但幅度未增加，表明该肽的作用位点在突触前。脑室内注射NPFF导致PVN附近的GABA能神经元激活，这通过Fos蛋白免疫组织化学和谷氨酸脱羧酶（GAD67）mRNA原位杂交得以揭示。基于这些观察结果，我们得出结论，NPFF通过位于核紧邻区域的GABA能中间神经元促进对PVN MNC的抑制性输入。这些发现为NPFF诱导的血管加压素释放抑制提供了细胞和解剖学基础，已有报道称低血容量和高渗刺激后会出现这种抑制。
