Stimulation of cloned human glucagon-like peptide 1 receptor expressed in HEK 293 cells induces cAMP-dependent activation of calcium-induced calcium release.
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.
Gromada
J
J
Novo Nordisk A/S, Copenhagen, Denmark.
Rorsman
P
P
Dissing
S
S
Wulff
B S
BS
D000109:Acetylcholine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002460:Cell Line; D003001:Cloning, Molecular; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D004622:Embryo, Mammalian; D005934:Glucagon / Q000494:pharmacology; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D004763:Glucagon-Like Peptides; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D007668:Kidney; D010446:Peptide Fragments / Q000494:pharmacology; D018027:Receptors, Glucagon / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism; D012433:Ryanodine / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology
D002121:Calcium Channel Blockers; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D010446:Peptide Fragments; D018027:Receptors, Glucagon; D011994:Recombinant Proteins; D013873:Thionucleotides; C055453:glucagon-like peptide 1 (7-36)amide; D012433:Ryanodine; C016957:adenosine-3',5'-cyclic phosphorothioate; D015759:Ionomycin; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D000242:Cyclic AMP; D000109:Acetylcholine; D002118:Calcium