Cloning and functional expression of a human glucagon-like peptide-1 receptor.
A human glucagon-like 1 peptide receptor has been cloned from the gastric tumor cell line HGT-1. The cDNA clone encodes a protein of 463 amino acids and is a member of the superfamily of seven transmembrane domain G protein coupled receptors. Transfection of the human GLP-1 receptor into COS-7 cells confers upon them high affinity binding for [125I] GLP-1 (7-36) amide. In membranes prepared from COS-7 cells transfected with the human GLP-1 receptor, the binding of [125I] GLP-1 (7-36) amide is inhibited with the rank order of potency GLP-1 (7-36) amide > glucagon > secretin, characteristic of a GLP-1 receptor. The human GLP-1 receptor is functionally coupled to increases in intracellular cAMP in these cells: incubation of COS-7 cells expressing the human GLP-1 receptor with GLP-1 (7-36) amide gives rise to a 4-fold increase in cyclic AMP over basal levels, with an EC50 of 25pM. Glucagon is also a full agonist but is 200-fold less potent than GLP-1 (7-36) amide in stimulating the human GLP-1 receptor.
Graziano
M P
MP
Department of Molecular Pharmacology and Biochemistry, Merck Research Laboratories, Rahway, NJ 07065.
Hey
P J
PJ
Borkowski
D
D
Chicchi
G G
GG
Strader
C D
CD
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D005934:Glucagon / Q000378:metabolism; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000145:classification / Q000235:genetics*; D018027:Receptors, Glucagon; D011994:Recombinant Proteins / Q000096:biosynthesis; D017386:Sequence Homology, Amino Acid; D014162:Transfection
D018076:DNA, Complementary; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D010446:Peptide Fragments; D011498:Protein Precursors; D011956:Receptors, Cell Surface; D018027:Receptors, Glucagon; D011994:Recombinant Proteins; D052216:Glucagon-Like Peptide 1; D005934:Glucagon