PYY3-36 inhibits the action potential firing activity of POMC neurons of arcuate nucleus through postsynaptic Y2 receptors
PYY3-36 inhibits the action potential firing activity of POMC neurons of arcuate nucleus through postsynaptic Y2 receptors
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DOI：
10.1016/j.cmet.2005.08.003
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发表时间：
2005-09-01
期刊：
影响因子：
29
通讯作者：
Cone, RD
中科院分区：
文献类型：
--
作者：
Ghamari-Langroudi, M;Colmers, WF;Cone, RD
脑室内给予肠肽 PYY3-36 可刺激食物摄入。相比之下，外周给药会抑制食物摄入，这表明该肽通过进入大脑部位的独特子集而具有相反的效果。先前的一项研究表明，外周 PYY3-36 激活弓状核中的厌食 POMC 神经元，这被认为是该肽厌食活性的机制。在这里，我们在电生理切片制备中证明，与原始模型相反，PYY3-36 通过突触后 Y-2 受体有效且可逆地抑制 POMC 神经元。这些数据显示 Y-2 受体在 NPY/POMC 回路调节中的复杂作用，因为它们作为抑制性受体存在于促食欲 NPY 神经元和厌食 POMC 神经元上。其次，这些数据反对 POMC 神经元在介导对外周 PYY3-36 给药的厌食反应中的直接作用。
Intracerebroventricular administration of gut peptide PYY3-36 stimulates food intake. In contrast, peripheral administration inhibits food intake, suggesting that the peptide has the opposite effect by virtue of accessing a unique subset of brain sites. A previous study suggested that peripheral PYY3-36 activates anorexigenic POMC neurons in the arcuate nucleus, and this was proposed to be the mechanism underlying the peptide's anorexigenic activity. Here, we demonstrate in an electrophysiological slice preparation that, in contrast to the original model, PYY3-36 potently and reversibly inhibits POMC neurons via postsynaptic Y-2 receptors. These data show a complex role for Y-2 receptors in regulation of the NPY/POMC circuitry, as they are present as inhibitory receptors on both the orexigenic NPY neurons as well as the anorexigenic POMC neurons. Secondly, these data argue against a direct role of POMC neurons in mediating the anorexigenic response to administration of peripheral PYY3-36.