Naturally occurring glucagon-like peptide-2 (GLP-2) receptors in human intestinal cell lines

被引:8
|
作者
Sams, A
Hastrup, S
Andersen, M
Thim, L
机构
[1] Novo Nordisk AS, Dept Mol Pharmacol, DK-2760 Malov, Denmark
[2] Novo Nordisk AS, Dept Microbial Cell Technol, DK-2760 Malov, Denmark
[3] Novo Nordisk AS, Dept Prot Engn, DK-2760 Malov, Denmark
关键词
GLP-2; receptor; G alpha protein signalling; intestinal growth; RT-PCR; western blot; cAMP;
D O I
10.1016/j.ejphar.2005.12.001
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Although clinical trials with GLP-2 receptor agonists are currently ongoing, the mechanisms behind GLP-2-induced intestinal epithelial growth remain to be understood. To approach the GLP-2 mechanism of action this study aimed to identify intestinal cell lines endogenously expressing the GLP-2 receptor. Here we report the first identification of a cell line endogenously expressing functional GLP-2 receptors. The human intestinal epithelial cell line, FHC, expressed GLP-2 receptor encoding mRNA (RT-PCR) and GLP-2 receptor protein (Western blot). In cultured FHC cells, GLP-2 induced concentration dependent cAMP accumulation (pEC50=9.7 +/- 0.04 (mean S.E.M., n=4)). In addition, a naturally occurring human intestinal fibroblast cell line, 18Co, endogenously expressing GLP-2 receptor encoding mRNA (RTPCR) and protein (Western blot) was identified. No receptor functionality (binding or G-protein signalling) could be demonstrated in 18Co cells. The identified gut-relevant cell lines provide tools for future clarification of the mechanisms underlying GLP-2-induced epithelial growth. (c) 2006 Elsevier B.V. All rights reserved.
引用
收藏
页码:18 / 23
页数:6
相关论文
共 50 条
  • [1] Glucagon-like peptide 2 (GLP-2), an intestinotrophic mediator
    Thulesen, J
    CURRENT PROTEIN & PEPTIDE SCIENCE, 2004, 5 (01) : 51 - 65
  • [2] The alpha cell expresses glucagon-like peptide-2 receptors and glucagon-like peptide-2 stimulates glucagon secretion from the rat pancreas
    J. de Heer
    J. Pedersen
    C. Ørskov
    J. J. Holst
    Diabetologia, 2007, 50 : 2135 - 2142
  • [3] The alpha cell expresses glucagon-like peptide-2 receptors and glucagon-like peptide-2 stimulates glucagon secretion from the rat pancreas
    de Heer, J.
    Pedersen, J.
    Orskov, C.
    Holst, J. J.
    DIABETOLOGIA, 2007, 50 (10) : 2135 - 2142
  • [4] Differential expression of glucagon-like peptide-2 (GLP-2) is involved in pancreatic islet cell adaptations to stress and beta-cell survival
    Khan, Dawood
    Vasu, Srividya
    Moffett, R. Charlotte
    Irwin, Nigel
    Flatt, Peter R.
    PEPTIDES, 2017, 95 : 68 - 75
  • [5] Synthesis and Pharmacological Characterization of Novel Glucagon-like Peptide-2 (GLP-2) Analogues with Low Systemic Clearance
    Wisniewski, Kazimierz
    Sueiras-Diaz, Javier
    Jiang, Guangcheng
    Galyean, Robert
    Lu, Mark
    Thompson, Dorain
    Wang, Yung-Chih
    Croston, Glenn
    Posch, Alexander
    Hargrove, Diane M.
    Wisniewska, Halina
    Laporte, Regent
    Dwyer, John J.
    Qi, Steve
    Srinivasan, Karthik
    Hartwig, Jennifer
    Ferdyan, Nicky
    Mares, Monica
    Kraus, John
    Alagarsamy, Sudarkodi
    Riviere, Pierre J. M.
    Schteingart, Claudio D.
    JOURNAL OF MEDICINAL CHEMISTRY, 2016, 59 (07) : 3129 - 3139
  • [6] The dimerization of glucagon-like peptide-2 MIMETIBODY™ is linked to leucine-17 in the glucagon-like peptide-2 region
    E. Baker, Audrey
    Sague, Sarah
    Grygiel, Tami L. R.
    Schmidt, Albert
    Rogers, Alison
    Jiang, Haiyan
    Kruszynski, Marian
    Nesspor, Tom
    JOURNAL OF MOLECULAR RECOGNITION, 2012, 25 (03) : 155 - 164
  • [7] Glucagon-like peptide-2 (GLP-2) response to enteral intake in children during anti-cancer treatment
    Andreassen, BU
    Pærregaard, A
    Schmiegelow, K
    Rechnitzer, C
    Heilman, C
    Hartmann, B
    Holst, JJ
    Michaelsen, KF
    JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION, 2005, 40 (01) : 48 - 53
  • [8] Glucagon-like peptide-1 and glucagon-like peptide-2 regulation during human liver regeneration
    Ammann, Markus
    Santol, Jonas
    Pereyra, David
    Kalchbrenner, Tamara
    Wuerger, Tanja
    Laengle, Johannes
    Smoot, Rory L.
    Hulla, Wolfgang
    Laengle, Friedrich
    Starlinger, Patrick
    SCIENTIFIC REPORTS, 2023, 13 (01)
  • [9] Intestinotrophic Glucagon-Like Peptide-2 (GLP-2) Activates Intestinal Gene Expression and Growth Factor-Dependent Pathways Independent of the Vasoactive Intestinal Peptide Gene in Mice
    Yusta, Bernardo
    Holland, Dianne
    Waschek, James A.
    Drucker, Daniel J.
    ENDOCRINOLOGY, 2012, 153 (06) : 2623 - 2632
  • [10] The "cryptic" mechanism of action of glucagon-like peptide-2
    Rowland, Katherine J.
    Brubaker, Patricia L.
    AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 2011, 301 (01): : G1 - G8