Stable expression of the rat GLP-I receptor in CHO cells: activation and binding characteristics utilizing GLP-I(7-36)-amide, oxyntomodulin, exendin-4, and exendin(9-39).
Glucagon-like peptide-I (GLP-I) is a potent insulinotropic peptide that mediates its actions at pancreatic B-cells via specific receptors. In the present study we stably expressed the rat B-cell GLP-I receptor in CHO cells and studied binding characteristics and receptor activation utilizing the naturally occurring receptor agonist GLP-I(7-36)-amide (GLP-I), the proglucagon-derived GLP-I-related peptide oxyntomodulin, the GLP-I receptor agonist exendin-4, and the specific antagonist exendin(9-39). The potencies to displace [125I]GLP-I from the receptor were GLP-I > exendin-4 > exendin(9-39) > oxyntomodulin, and to displace [125I]exendin-4 GLP-I = exendin-4 > exendin(9-39) > oxyntomodulin. cAMP production was stimulated equally by GLP-I and exendin-4. Oxyntomodulin was less potent to stimulate cAMP generation. Exendin(9-39) blocked the stimulatory action of GLP-I and exendin-4 on cAMP production, but not that of oxyntomodulin. This study shows that GLP-I and exendin-4 are potent agonists at the transfected rat B-cell GLP-I receptor whereas oxyntomodulin is only a weak GLP-I receptor agonist. Furthermore, exendin(9-39) is a potent GLP-I receptor antagonist. This peptide is a valuable tool to further study the physiological actions of GLP-I.
Fehmann
H C
HC
Department of Medicine, Philipps-University of Marburg, Germany.
Jiang
J
J
Schweinfurth
J
J
Wheeler
M B
MB
Boyd
A E
AE
Göke
B
B
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D005069:Evaluation Studies as Topic; D000077270:Exenatide; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D004763:Glucagon-Like Peptides / Q000378:metabolism; D008116:Lizards; D018377:Neurotransmitter Agents / Q000378:metabolism; D053772:Oxyntomodulin; D010446:Peptide Fragments / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D051381:Rats / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018027:Receptors, Glucagon; D014688:Venoms
C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D018377:Neurotransmitter Agents; D053772:Oxyntomodulin; D010446:Peptide Fragments; D010455:Peptides; D011956:Receptors, Cell Surface; D018027:Receptors, Glucagon; D014688:Venoms; C055453:glucagon-like peptide 1 (7-36)amide; C083773:exendin (9-39); D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D000077270:Exenatide