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 (K-d = 0.76 nM). Binding of GLP-1(7-36)amide stimulated cAMP production in a dose-dependent manner (EC(50) = 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.