Neuropeptide Y inhibits [Ca2+]i changes in rat retinal neurons through NPY Y1, Y4, and Y5 receptors
Neuropeptide Y inhibits [Ca2+]i changes in rat retinal neurons through NPY Y1, Y4, and Y5 receptors
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DOI：
10.1111/j.1471-4159.2009.06079.x
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发表时间：
2009-06-01
影响因子：
4.7
通讯作者：
Cavadas, Claudia
中科院分区：
文献类型：
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作者：
Alvaro, Ana Rita;Rosmaninho-Salgado, Joana;Cavadas, Claudia
神经肽Y（NPY）和NPY受体广泛分布在中枢神经系统中，包括视网膜，但NPY在视网膜中的作用很大程度上未知。本研究的目的是研究 NPY 是否调节视网膜神经元细胞内钙浓度 ([Ca2+](i)) 的变化，并鉴定相关的 NPY 受体。由于 NPY 仅在 50% 的分析神经元中降低了 30 mM KCl 诱发的 [Ca2+](i) 振幅，因此我们将它们分为两个群体：NPY 无反应神经元 (Delta 2/Delta 1 >= 0.80) 和 NPY 反应神经元 (Delta 2/Delta 1 < 0.80)，Delta 2/Delta 1 是KCl 的第二次 (Delta 2) 和第一次 (Delta 1) 刺激引起 [Ca2+](i) 增加。 NPY Y-1/Y-5、Y-4 和 Y-5 受体激动剂 (100 nM)，但不抑制 Y-2 受体激动剂 (300 nM)，抑制 KCl 诱导的 [Ca2+](i) 增加。此外，在 Y-1 或 Y-5 受体拮抗剂存在下，NPY 对诱发的 -[Ca2+](i) 变化的抑制作用降低。总之，NPY 通过激活 NPY Y-1、Y-4 和 Y-5 受体来抑制 KCl 诱发的视网膜神经元 [Ca2+](i) 增加。这种作用可能被视为 NPY 对抗视网膜神经变性的潜在神经保护机制。
Neuropeptide Y (NPY) and NPY receptors are widely distributed in the CNS, including the retina, but the role of NPY in the retina is largely unknown. The aim of this study was to investigate whether NPY modulates intracellular calcium concentration ([Ca2+](i)) changes in retinal neurons and identify the NPY receptors involved. As NPY decreased the [Ca2+](i) amplitudes evoked by 30 mM KCl in only 50% of neurons analyzed, we divided them in two populations: NPY-non-responsive neurons (Delta 2/Delta 1 >= 0.80) and NPY-responsive neurons (Delta 2/Delta 1 < 0.80), being the Delta 2/Delta 1 the ratio between the amplitude of [Ca2+](i) increase evoked by the second (Delta 2) and the first (Delta 1) stimuli of KCl. The NPY Y-1/Y-5, Y-4, and Y-5 receptor agonists (100 nM), but not the Y-2 receptor agonist (300 nM), inhibited the [Ca2+](i) increase induced by KCl. In addition, the inhibitory effect of NPY on evoked-[Ca2+](i) changes was reduced in the presence of the Y-1 or the Y-5 receptor antagonists. In conclusion, NPY inhibits KCl-evoked [Ca2+](i) increase in retinal neurons through the activation of NPY Y-1, Y-4, and Y-5 receptors. This effect may be viewed as a potential neuroprotective mechanism of NPY against retinal neurodegeneration.