Cocaine- and Amphetamine-Regulated Transcript Mediates the Actions of Cholecystokinin on Rat Vagal Afferent Neurons
Cocaine- and Amphetamine-Regulated Transcript Mediates the Actions of Cholecystokinin on Rat Vagal Afferent Neurons
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DOI：
10.1053/j.gastro.2009.10.034
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发表时间：
2010-04-01
期刊：
影响因子：
29.4
通讯作者：
Dockray, Graham J.
中科院分区：
文献类型：
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作者：
De Lartigue, Guillaume;Dimaline, Rod;Dockray, Graham J.
背景与目的：CCK作用于迷走神经传入神经元，抑制食物摄取和胃排空，也可增加神经肽可卡因和苯丙胺调节转录本(CART)的表达，但其意义尚不清楚。我们研究了CARTp在迷走神经传入神经元中的作用。方法：用酶联免疫吸附试验测定培养的迷走神经传入神经元释放CARTp。应用免疫组织化学和荧光素酶启动子报告载体研究CARTp对大鼠迷走神经传入神经元受体和神经肽表达的影响。研究CARTP和CCK对大鼠摄食量的影响。结果：CCK可刺激结节神经元释放CARTp。CARTp在体内和体外复制了CCK刺激Y2R和CART本身在这些神经元中表达的作用，但不抑制大麻素-1、黑色素浓缩激素和黑色素浓缩激素-1受体的表达。CCK对Y2R和CART表达的影响可被CART小干扰RNA或灯盏花素A减弱。CARTp可增加大鼠短期禁食后CCK对食物摄取的抑制作用，而不是长期禁食。结论：CARTp可增强CCK刺激迷走神经传入神经元CART和Y2R表达及抑制摄食的作用，CCK可从这些神经元释放CARTp，提示CCK是一种自分泌的兴奋性介质。
BACKGROUND & AIMS: Cholecystokinin (CCK) acts on vagal afferent neurons to inhibit food intake and gastric emptying; it also increases expression of the neuropeptide cocaine-and amphetamine-regulated transcript (CART), but the significance of this is unknown. We investigated the role of CARTp in vagal afferent neurons. METHODS: Release of CART peptide (CARTp) from cultured vagal afferent neurons was determined by enzyme-linked immunosorbent assay. Expression of receptors and neuropeptides in rat vagal afferent neurons in response to CARTp was studied using immunohistochemistry and luciferase promoter reporter constructs. Effects of CARTp and CCK were studied on food intake. RESULTS: CCK stimulated CARTp release from cultured nodose neurons. CARTp replicated the effect of CCK in stimulating expression of Y2R and of CART itself in these neurons in vivo and in vitro, but not in inhibiting cannabinoid-1, melanin-concentrating hormone, and melanin-concentrating hormone-1 receptor expression. Effects of CCK on Y2R and CART expression were reduced by CART small interfering RNA or brefeldin A. Exposure of rats to CARTp increased the inhibitory action of CCK on food intake after short-, but not long-duration, fasting. CONCLUSIONS: The actions of CCK in stimulating CART and Y2R expression in vagal afferent neurons and in inhibiting food intake are augmented by CARTp; CARTp is released by CCK from these neurons, indicating that it acts as an autocrine excitatory mediator.