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Signaling in Rat Brainstem via Gpr160 is Required for the Anorexigenic and Antidipsogenic Actions of Cocaine- and Amphetamine-Regulated Transcript Peptide
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology ( IF 2.8 ) Pub Date : 2020-11-18 , DOI: 10.1152/ajpregu.00096.2020
Christopher J Haddock 1 , Gislaine Almeida-Pereira 1 , Lauren M Stein 2 , Matthew R Hayes 2 , Grant R Kolar 3 , Willis K Samson 1 , Gina L C Yosten 1
Affiliation  

Recent work identified Gpr160 as a candidate receptor for cocaine- and amphetamine-regulated transcript peptide (CARTp) and described its role in pain modulation. The aims of the present study were to determine if Gpr160 is required for the CARTp's ability to reduce food and water intake and to initially identify the distribution of Gpr160-like immunoreactivity (Gpr160ir) in the rat brain. A passive immunoneutralization approach targeting Gpr160 was used to block the behavioral effects of a pharmacologic dose of CARTp in the fourth cerebroventricle (4V) of rats and to determine the importance of endogenously produced CARTp in the control of ingestive behaviors. Passive immunoneutralization of Gpr160 in the 4V blocked the actions of CARTp to inhibit food and water intakes. Blockade of Gpr160 in the 4V, independent of pharmacologic CART treatment, caused an increase in both overnight food and water intakes. The decrease in food, but not water intake, caused by central injection of CARTp was demonstrated to be interrupted by prior administration of a GLP-1 receptor antagonist. Gpr160ir was observed in several, distinct sites throughout the rat brain, where CARTp staining has been described. Importantly, Gpr160ir was observed to be present in both neuronal and non-neuronal cell types. These data support the hypothesis that Gpr160 is required for the anorexigenic actions of central CARTp injection, and extend these findings to water drinking. Gpr160ir was observed in both neuronal and non-neuronal cell types in regions known to be important in the multiple pharmacologic effects of CARTp, identifying those areas as targets for future compromise of function studies.

中文翻译:

可卡因和安非他明调节的转录肽的厌食和抗过敏作用需要通过 Gpr160 在大鼠脑干中发出信号

最近的工作将 Gpr160 确定为可卡因和苯丙胺调节转录肽 (CARTp) 的候选受体,并描述了其在疼痛调节中的作用。本研究的目的是确定 CARTp 减少食物和水摄入的能力是否需要 Gpr160,并初步确定 Gpr160 样免疫反应性 (Gpr160ir) 在大鼠脑中的分布。一种针对 Gpr160 的被动免疫中和方法被用于阻断药理学剂量的 CARTp 在大鼠第四脑室 (4V) 中的行为影响,并确定内源性产生的 CARTp 在控制摄取行为中的重要性。4V 中 Gpr160 的被动免疫中和阻断了 CARTp 抑制食物和水摄入的作用。Gpr160在4V的封锁,独立于药物 CART 治疗,导致夜间食物和水摄入量的增加。由中央注射 CARTp 引起的食物摄入量减少,而不是水摄入量减少被证明被先前施用的 GLP-1 受体拮抗剂中断。Gpr160ir 在大鼠大脑中的几个不同部位观察到,其中描述了 CARTp 染色。重要的是,观察到 Gpr160ir 存在于神经元和非神经元细胞类型中。这些数据支持 Gpr160 是中央 CARTp 注射的厌食作用所必需的假设,并将这些发现扩展到饮水。在已知对 CARTp 的多种药理作用很重要的区域,在神经元和非神经元细胞类型中均观察到 Gpr160ir,
更新日期:2020-11-19
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