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.