A reassessment of structure-function relationships in glucagon. Glucagon_1-21 is a full agonist

Glucagon_1-21 has been prepared by treating native glucagon with carboxypeptidase A. Purified glucagon_1-21 did not contain detectable methionine (<0.001 residue/mol) and the activity of the compound did not change after treatment with cyanogen bromide as has been shown with native glucagon. Glucagon_1-21 stimulates hepatic adenylate cyclase activity to the same extent as native glucagon but with 0.1% the potency. Glucagon_1-21 also displayed 0.1% the binding affinity of native glucagon to the glucagon receptor in hepatic membranes. Glucagon_22-29 alone or in combination with glucagon_1-21 did not activate adenylate cyclase or displace ¹²⁵I-glucagon from its receptor. The finding that glucagon_1-21 is a full agonist on adenylate cyclase is discussed in relation to the structure-function relationships required for the biological action of glucagon.