Obestatin does not activate orphan G protein-coupled receptor GPR39

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• 作者：Erwin Lauwers ; Bart Landuyt ; Lutgarde Arckens ; Liliane Schoofs and Walter Luyten
• 关键词：Obestatin ; GPR39 ; GPCR
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2006
• 期刊代码：159_0006291x
• 类别：bio
• 出版时间：8 December 2006
• 卷：351
• 期：1
• 页码：21-25
• 文件大小：831 K

摘要

Recently, the ligand of the orphan G protein-coupled receptor GPR39 has been identified as obestatin, a 23-amino acid peptide derived from the ghrelin precursor protein. We used two methods to study the possible activation of GPR39 by obestatin: cAMP measurements based on a luminescent reporter gene and a fluorometric Ca²⁺ flux method. The former was similar to that reported in the original publication of Zhang et al. [J.V. Zhang, P.G. Ren, O. Avsian-Kretchmer, C.W. Luo, R. Rauch, C. Klein, Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin’s effects on food intake, Science 310 (2005) 996–999]. The latter method used promiscuous as well as chimaeric G-proteins commonly used to couple orphan G protein-coupled receptors to the phospholipase C pathway, that leads to intracellular Ca²⁺ rise. We could, however, not demonstrate activation of the GPR39 receptor by obestatin via any of these signal transduction pathways. We could activate GPR39 by high concentrations of Zn²⁺, demonstrating cell surface expression of a functional receptor that could elicit a Ca²⁺ response. The Zn²⁺ response was not affected by obestatin. The identity of the native ligand for GPR39 remains to be elucidated.