Receptor binding and cell-mediated metabolism of [125I]monoiodoglucagon by isolated canine hepatocytes

A reverse-phase HPLC method has been developed to purify 125I-labeled products resulting from the chloramine-T-based iodination of glucagon. In addition the products [(125I)iodoTyr1013]glucagon, [(125I)iodoTyr13]glucagon, and [(125I)iodoTyr10]glucagon) have been used to study the receptor binding of glucagon and the cell-mediated metabolism of the hormone by isolated canine hepatocytes. It was concluded that (a) not withstanding apparent differences in affinities exhibited by the three peptides, the interactions with the glucagon receptor are functionally equivalent, and (b) the cell-mediated metabolism of receptor-bound glucagon involves the formation of hormone-derived peptides in which the biologically important NH2-terminal region of the hormone has been modified by limited proteolytic cleavage