Neuromedin B and gastrin-releasing peptide excite arcuate nucleus neuropeptide Y neurons in a novel transgenic mouse expressing strong Renilla green fluorescent protein in NPY neurons.
Neuromedin B and gastrin-releasing peptide excite arcuate nucleus neuropeptide Y neurons in a novel transgenic mouse expressing strong Renilla green fluorescent protein in NPY neurons.
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DOI：
10.1523/jneurosci.3249-08.2009
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发表时间：
2009-04-08
期刊：
影响因子：
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通讯作者：
Broberger C
中科院分区：
文献类型：
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作者：
van den Pol AN;Yao Y;Fu LY;Foo K;Huang H;Coppari R;Lowell BB;Broberger C
神经肽Y（neuropeptide Y，NPY）是脑内分布最广泛的神经肽之一。转基因小鼠的产生，表达明亮的海肾GFP在大多数或所有已知的神经肽Y细胞在大脑中，否则是不可识别的。免疫细胞化学和单细胞RT-PCR证实GFP在NPY细胞中的表达。下丘脑弓状核内的NPY神经元在能量平衡和内分泌调节中起重要作用。全细胞膜片钳记录用于研究所鉴定的弓状NPY细胞。调节能量平衡的主要药物包括黑皮质素受体激动剂、AgRP和大麻素;这些物质基本上都不影响NPY神经元的电特性。与此形成鲜明对比的是，蛙皮素家族的神经肽，包括在弓状核的轴突中发现的胃泌素释放肽和神经介肽B，也可以从肠道释放以向大脑发出信号，在纳摩尔水平上对NPY神经元表现出强烈的直接兴奋作用，比生长素释放肽和下丘脑泌素/食欲素的作用更强。蛙皮素相关肽降低输入阻力和去极化膜电位。去极化被几个因素减弱：胆碱替代钠，细胞外Ni 2+，在移液管中包含BAPTA，KB-R7943和SKF 96365。细胞外钙离子的减少增强了电流，电流在-20 mV左右逆转。总之，这些数据表明两种机制，非选择性阳离子通道和钠/钙交换剂的激活。由于NPY和POMC神经元，我们也研究，同样直接兴奋的蛙皮素样肽，肽的功能，以启动广泛的激活，而不是细胞类型的选择性激活或抑制许多其他化合物，调节能量稳态。
Neuropeptide Y (NPY) is one of the most widespread neuropeptides in the brain. Transgenic mice were generated that expressed bright renilla GFP in most or all of the known NPY cells in the brain, which otherwise were not identifiable. GFP expression in NPY cells was confirmed with immunocytochemistry and single cell RT-PCR. NPY neurons in the hypothalamic arcuate nucleus play an important role in energy homeostasis and endocrine control. Whole cell patch clamp recording was used to study identified arcuate NPY cells. Primary agents that regulate energy balance include melanocortin receptor agonists, AgRP, and cannabinoids; none of these substances substantially influenced electrical properties of NPY neurons. In striking contrast, neuropeptides of the bombesin family, including gastrin releasing peptide and neuromedin B which are found in axons in the arcuate nucleus and may also be released from the gut to signal the brain, showed strong direct excitatory actions at nanomolar levels on the NPY neurons, stronger than the actions of ghrelin and hypocretin/orexin. Bombesin-related peptides reduced input resistance and depolarized the membrane potential. The depolarization was attenuated by several factors: substitution of choline for sodium, extracellular Ni2+, inclusion of BAPTA in the pipette, KB-R7943 and SKF96365. Reduced extracellular calcium enhanced the current, which reversed around − 20 mV. Together, these data suggest two mechanisms, activation of non-selective cation channels and the sodium/calcium exchanger. Since both NPY and POMC neurons, which we also studied, are similarly directly excited by bombesin-like peptides, the peptides may function to initiate broad activation, rather than the cell-type selective activation or inhibition reported for many other compounds that modulate energy homeostasis.