Obestatin does not activate orphan G protein-coupled receptor GPR39

被引:207
作者
Lauwers, Erwin
Landuyt, Bart
Arckens, Lutgarde
Schoofs, Liliane
Luyten, Walter
机构
[1] Katholieke Univ Leuven, Lab Dev Physiol Genom & Proteom, B-3000 Louvain, Belgium
[2] Katholieke Univ Leuven, Sch Med, Dept Gynaecol, B-3000 Louvain, Belgium
[3] Katholieke Univ Leuven, Lab Neuroplasticity & Neuroproteom, B-3000 Louvain, Belgium
关键词
obestatin; GPR39; GPCR;
D O I
10.1016/j.bbrc.2006.09.141
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
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. (c) 2006 Elsevier Inc. All rights reserved.
引用
收藏
页码:21 / 25
页数:5
相关论文
共 9 条
[1]   Common structural basis for constitutive activity of the ghrelin receptor family [J].
Holst, B ;
Holliday, ND ;
Bach, A ;
Elling, CE ;
Cox, HM ;
Schwartz, TW .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (51) :53806-53817
[2]   Metal ion-mediated agonism and agonist enhancement in melanocortin MC1 and MC4 receptors [J].
Holst, B ;
Elling, CE ;
Schwartz, TW .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (49) :47662-47670
[3]   GPR39 receptor expression in the mouse brain [J].
Jackson, Valerie R. ;
Nothacker, Hans-Peter ;
Civelli, Olivier .
NEUROREPORT, 2006, 17 (08) :813-816
[4]   Cloning and characterization of two human G protein-coupled receptor genes (GPR38 and GPR39) related to the growth hormone secretagogue and neurotensin receptors [J].
McKee, KK ;
Tan, CP ;
Palyha, OC ;
Liu, J ;
Feighner, SD ;
Hreniuk, DL ;
Smith, RG ;
Howard, AD ;
Van der Ploeg, LHT .
GENOMICS, 1997, 46 (03) :426-434
[5]   Characterization of the short neuropeptide F receptor from Drosophila melanogaster [J].
Mertens, I ;
Meeusen, T ;
Huybrechts, R ;
De Loof, A ;
Schoofs, L .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2002, 297 (05) :1140-1148
[6]  
Roelant CH, 1996, BIOTECHNIQUES, V20, P914
[7]   Natural agonist enhancing bis-His zinc-site in transmembrane segment V of the tachykinin NK3 receptor [J].
Rosenkilde, MM ;
Lucibello, M ;
Holst, B ;
Schwartz, TW .
FEBS LETTERS, 1998, 439 (1-2) :35-40
[8]   Allosteric modulation of β2-adrenergic receptor by Zn2+ [J].
Swaminath, G ;
Steenhuis, J ;
Kobilka, B ;
Lee, TW .
MOLECULAR PHARMACOLOGY, 2002, 61 (01) :65-72
[9]   Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's effects on food intake [J].
Zhang, JV ;
Ren, PG ;
Avsian-Kretchmer, O ;
Luo, CW ;
Rauch, R ;
Klein, C ;
Hsueh, AJW .
SCIENCE, 2005, 310 (5750) :996-999