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 pept ide-1 (GLP-1) receptor was studied in voltage-clamped Xenopus oocytes. Binding of GLP-1(7-36)amide was associated with cAMP production, incr eased [Ca2+](i) and activation of Ca2+-dependent Cl- current. The effe ct of GLP-1(7-36)amide reflects intracellular Ca2+ mobilization and wa s suppressed by injection of the Ca2+ chelator BAPTA and the inositol trisphosphate receptor antagonist heparin. The responses were not mimi cked by the adenylate cyclase activator forskolin and unaffected by th e protein kinase A (PKA) inhibitor Rp-cAMPS. We conclude that GLP-1 re ceptor expression in Xenopus oocytes evokes inositol trisphosphate-dep endent intracellular Ca2+ mobilization independent of the cAMP/PKA sig naling pathway. (C) 1998 Federation of European Biochemical Societies.