Abstract
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 (Kd = 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 Ca(2+)-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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylcholine / pharmacology
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Calcium / metabolism*
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Calcium / pharmacology
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Calcium Channel Blockers / pharmacology
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Cell Line
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Cloning, Molecular
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Cyclic AMP / analogs & derivatives
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Cyclic AMP / metabolism*
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Cyclic AMP / pharmacology
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Embryo, Mammalian
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Glucagon / pharmacology
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Glucagon-Like Peptide 1
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Glucagon-Like Peptide-1 Receptor
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Glucagon-Like Peptides
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Humans
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Ionomycin / pharmacology
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Kidney
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Peptide Fragments / pharmacology
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Receptors, Glucagon / biosynthesis
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Receptors, Glucagon / drug effects
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Receptors, Glucagon / physiology*
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Recombinant Proteins / biosynthesis
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Recombinant Proteins / drug effects
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Recombinant Proteins / metabolism
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Ryanodine / pharmacology
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Thionucleotides / pharmacology
Substances
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Calcium Channel Blockers
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GLP1R protein, human
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Glucagon-Like Peptide-1 Receptor
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Peptide Fragments
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Receptors, Glucagon
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Recombinant Proteins
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Thionucleotides
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glucagon-like peptide 1 (7-36)amide
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Ryanodine
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adenosine-3',5'-cyclic phosphorothioate
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Ionomycin
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Glucagon-Like Peptides
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Glucagon-Like Peptide 1
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Glucagon
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Cyclic AMP
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Acetylcholine
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Calcium