GPR39 signaling is stimulated by zinc ions but not by obestatin
GPR39 signaling is stimulated by zinc ions but not by obestatin
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DOI：
10.1210/en.2006-0933
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发表时间：
2007-01-01
期刊：
影响因子：
4.8
通讯作者：
Schwartz, Thue W.
中科院分区：
文献类型：
--
作者：
Holst, Birgitte;Egerod, Kristoffer L.;Schwartz, Thue W.
GPR39是Ghrelin受体家族中的一个孤儿成员，最近被认为是由Ghrelin前体衍生的多肽Obe statin的受体。在这里，我们比较了他汀类药物和锌离子对信号转导的影响，并研究了他汀类药物对食物摄入量的影响。尽管锌离子刺激GPR39表达细胞的肌醇磷酸转换、cAMP生成、arrestin动员以及cAMP反应元件依赖和血清反应元件依赖的转录活性，但在表达GPR39的细胞中，他汀类药物不能获得可复制的作用。此外，在两种不同类型的表达GPR39的细胞中，用三种不同的放射性碘化形式的奥贝抑素都不能检测到与其特异的结合。定量聚合酶链式反应分析发现，GPR39在十二指肠和肾脏等外周器官中表达，而在脑垂体和下丘脑中不表达，即推测为obstatin的中枢靶器官。无论是自由喂养的还是禁食的瘦小鼠，奥斯汀对急性摄食量都没有显著且可重复性的影响。结论：GPR39可能不是奥贝他汀受体。相反，锌离子在激活信号方面的效力和效果表明，这种金属离子可能是GPR39的生理相关激动剂或调节剂。
GPR39 is an orphan member of the ghrelin receptor family that recently was suggested to be the receptor for obestatin, a peptide derived from the ghrelin precursor. Here, we compare the effect of obestatin to the effect of Zn2+ on signal transduction and study the effect of obestatin on food intake. Although Zn2+ stimulated inositol phosphate turnover, cAMP production, arrestin mobilization, as well as cAMP response element-dependent and serum response element-dependent transcriptional activity in GPR39-expressing cells as opposed to mock-transfected cells, no reproducible effect was obtained with obestatin in the GPR39-expressing cells. Moreover, no specific binding of obestatin could be detected in two different types of GPR39-expressing cells using three different radioiodinated forms of obestatin. By quantitative PCR analysis, GPR39 expression was readily detected in peripheral organs such as duodenum and kidney but not in the pituitary and hypothalamus, i.e. presumed central target organs for obestatin. Obestatin had no significant and reproducible effect on acute food intake in either freely fed or fasted lean mice. It is concluded that GPR39 is probably not the obestatin receptor. In contrast, the potency and efficacy of Zn2+ in respect of activating signaling indicates that this metal ion could be a physiologically relevant agonist or modulator of GPR39.