Stimulation of cloned human glucagon‐like peptide 1 receptor expressed in HEK 293 cells induces cAMP‐dependent activation of calcium‐induced calcium release

FEBS Letters

Gromada, Jesper¹  Rorsman, Patrik¹  Dissing, Steen³  Wulff, Birgitte S.² 

[1] Islet Cell Physiology, Symbion Science Park, Novo Nordisk A/S, Fruebjergvej 3, DK-2100 Copenhagen, Denmark;Department of Molecular Pharmacology, Novo Nordisk A/S, Novo Allé, DK-2880 Bagsvaerd, Denmark;Department of Medical Physiology, The Panum Institute, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen, Denmark

关键词: GLP-1 receptor;    Calcium;    cAMP;    HEK 293 cell;    CICR;   

DOI  :  10.1016/0014-5793(95)01070-U

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The actions of glucagon-like peptide-1(7–36)amide (GLP-1(7–36)amide) on cellular signalling were studied in human embryonal kidney 293 (HEK 293) cells stably transfected with the cloned human GLP-1 receptor. The cloned GLP-1 receptor showed a single high-affinity binding site (K _d = 0.76 nM). Binding of GLP-1(7–36)amide stimulated cAMP production in a dose-dependent manner (EC₅₀ = 0.015 nM) and caused an increase in the intracellular free Ca²⁺ concentration ([Ca²⁺]_i). The latter effect reflected Ca²⁺-induced Ca²⁺ release and was suppressed by ryanodine. We propose that the ability of GLP-1(7–36)amide to increase [Ca²⁺]_i results from sensitization of the ryanodine receptors by a protein kinase A dependent mechanism.

【 授权许可】

Unknown