Elsevier

Peptides

Volume 15, Issue 3, 1994, Pages 453-456
Peptides

Article
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)

https://doi.org/10.1016/0196-9781(94)90204-6Get rights and content

Abstract

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 occuring 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.

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