Glucagon-like peptide-1 receptor expression in Xenopus oocytes stimulates inositol trisphosphate-dependent intracellular Ca2+ mobilization.
The signal transduction pathway of the cloned human glucagon-like peptide-1 (GLP-1) receptor was studied in voltage-clamped Xenopus oocytes. Binding of GLP-1(7-36)amide was associated with cAMP production, increased [Ca2+]i and activation of Ca2+-dependent Cl- current. The effect of GLP-1(7-36)amide reflects intracellular Ca2+ mobilization and was suppressed by injection of the Ca2+ chelator BAPTA and the inositol trisphosphate receptor antagonist heparin. The responses were not mimicked by the adenylate cyclase activator forskolin and unaffected by the protein kinase A (PKA) inhibitor Rp-cAMPS. We conclude that GLP-1 receptor expression in Xenopus oocytes evokes inositol trisphosphate-dependent intracellular Ca2+ mobilization independent of the cAMP/PKA signaling pathway.
Gromada
J
J
Department of Islet Cell Physiology, Novo Nordisk A/S, Symbion, Copenhagen, Denmark. JLG@novo.dk
Anker
C
C
Bokvist
K
K
Knudsen
L B
LB
Wahl
P
P
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D018118:Chloride Channels / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D015870:Gene Expression; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D007424:Intracellular Fluid; D009865:Oocytes / Q000378:metabolism; D018027:Receptors, Glucagon / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000378:metabolism
D018118:Chloride Channels; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D018027:Receptors, Glucagon; D015544:Inositol 1,4,5-Trisphosphate; D017868:Cyclic AMP-Dependent Protein Kinases; D000262:Adenylyl Cyclases; D002118:Calcium