Truncated glucagon-like peptide-1 interacts with exendin receptors on dispersed acini from Guinea pig pancreas: Identification of a mammalian analogue of the reptilian peptide exendin-4

To find mammalian analogues of exendin-4, a peptide from Helodermatidae venoms that interacts with newly discovered exendin receptors on dispersed acini from guinea pig pancreas, we examined the actions of recent additions to the vasoactive intestinal peptide/ secretin/glucagon family of regulatory peptides. In every respect tested, the truncated form of glucagon-like peptide-1, GLP-1(7-36)NH₂, mimicked the actions of exendin-4. Like exendin-4, GLP-1(7-3G)NH₂ caused an increase in acinar cAMP without stimulating amylase release. GLP-1(7-36)NH₂-induced increases in cAMP were inhibited progressively by increasing concentrations of the specific exendin-receptor antagonist, exendin(9-39)NH₂. In dispersed acini from guinea pig and rat pancreas, concentrations of GLP-1(7-3G)NH₂ that stimulated increases in cAMP caused potentiation of cholecystokinin-induced amylase release. Binding of ¹²⁵I-[Y³⁹]exendin-4 or ¹²⁵I-GLP-1(7-36)NH₂ to dispersed acini from guinea pig pancreas was inhibited by adding increasing concentrations of unlabeled exendin-4 or GLP-1(7-3G)NH₂. We conclude that the mammalian peptide GLP-1(7-3G)NH₂ interacts with exendin receptors on dispersed acini from guinea pig pancreas. Exendin(9-39)NH₂, a competitive antagonist of the actions of GLP-1(7-3G)NH₂ in pancreatic acini, may be a useful tool for examining the physiological actions of this peptide.