A neuropeptide ligand of the G protein-coupled receptor GPR103 regulates feeding, behavioral arousal, and blood pressure in mice
A neuropeptide ligand of the G protein-coupled receptor GPR103 regulates feeding, behavioral arousal, and blood pressure in mice
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DOI：
10.1073/pnas.0602371103
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发表时间：
2006-05-09
影响因子：
11.1
通讯作者：
Sakai, Juro
中科院分区：
文献类型：
--
作者：
Takayasu, Shinobu;Sakurai, Takeshi;Sakai, Juro
在这里，我们报道了从大鼠脑中分离和表征GPR103的内源性肽配体。纯化后的肽为43个残基的rf酰胺肽QRFP。我们还描述了人类GPR103的两个小鼠同源物，称为小鼠GPR103A和GPR103B。QRFP结合并激活人GPR103，以及小鼠GPR103A和GPR103B，在转染细胞中具有纳摩尔亲和力。小鼠大脑系统原位杂交分析显示，QRFP仅在脑室周围和下丘脑外侧表达，而这两种受体mrna明显定位于不同的脑区，彼此之间没有重叠。当集中给药小鼠时，QRFP诱导摄食行为，同时增加一般运动活动和代谢率。通过预先给药BIBP3226（一种Y1神经肽Y受体的特异性拮抗剂）来消除qrfp诱导的食物摄入。在ob/ob和db/db小鼠中，下丘脑pre - pro- qrfp mRNA的表达在禁食和遗传性肥胖小鼠中上调。中央给予QRFP也引起血压和心率的高度持续升高。我们的研究结果表明，QRFP和GPR103A/B可能调节多种神经内分泌和行为功能，并参与该神经肽系统在代谢综合征中的作用。
Here, we report the isolation and characterization of an endogenous peptide ligand of GPR103 from rat brains. The purified peptide was found to be the 43-residue RF-amide peptide QRFP. We also describe two mouse homologues of human GPR103, termed mouse GPR103A and GPR103B. QRFP binds and activates the human GPR103, as well as mouse GPR103A and GPR103B, with nanomolar affinities in transfected cells. Systematic in situ hybridization analysis in mouse brains showed that QRFP is expressed exclusively in the periventricular and lateral hypothalamus, whereas the two receptor mRNAs are distinctly localized in various brain areas without an overlap to each other. When administered centrally in mice, QRFP induced feeding behavior, accompanied by increased general locomotor activity and metabolic rate. QRFP-induced food intake was abolished by preadministration of BIBP3226, a specific antagonist for the Y1 neuropeptide Y receptor. Hypothalamic prepro-QRFP mRNA expression was up-regulated upon fasting and in genetically obese ob/ob and db/db mice. Central QRFP administration also evoked highly sustained elevation of blood pressure and heart rate. Our findings suggest that QRFP and GPR103A/B may regulate diverse neuroendocrine and behavioral functions and implicate this neuropeptide system in metabolic syndrome.