Stimulation of cloned human glucagon-like peptide 1 receptor expressed in HEK 293 cells induces cAMP-dependent activation of calcium-induced calcium release

FEBS Lett. 1995 Oct 9;373(2):182-6. doi: 10.1016/0014-5793(95)01070-u.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Calcium / metabolism*
  • Calcium / pharmacology
  • Calcium Channel Blockers / pharmacology
  • Cell Line
  • Cloning, Molecular
  • Cyclic AMP / analogs & derivatives
  • Cyclic AMP / metabolism*
  • Cyclic AMP / pharmacology
  • Embryo, Mammalian
  • Glucagon / pharmacology
  • Glucagon-Like Peptide 1
  • Glucagon-Like Peptide-1 Receptor
  • Glucagon-Like Peptides
  • Humans
  • Ionomycin / pharmacology
  • Kidney
  • Peptide Fragments / pharmacology
  • Receptors, Glucagon / biosynthesis
  • Receptors, Glucagon / drug effects
  • Receptors, Glucagon / physiology*
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / drug effects
  • Recombinant Proteins / metabolism
  • Ryanodine / pharmacology
  • Thionucleotides / pharmacology

Substances

  • Calcium Channel Blockers
  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Peptide Fragments
  • Receptors, Glucagon
  • Recombinant Proteins
  • Thionucleotides
  • glucagon-like peptide 1 (7-36)amide
  • Ryanodine
  • adenosine-3',5'-cyclic phosphorothioate
  • Ionomycin
  • Glucagon-Like Peptides
  • Glucagon-Like Peptide 1
  • Glucagon
  • Cyclic AMP
  • Acetylcholine
  • Calcium