The effect of C-terminus and N-terminus iodination on avian pancreatic polypeptide (APP) binding to its chicken brain...

In previous studies, membranes from chicken gastrointestinal tissues failed to bind appreciable levels of 125I-APP labeled at the C-terminus. In order to address the suggestion that this was due to steric hindrance of the critical C-terminus, N-terminally labeled 125I-APP was utilized in in vitro membrane binding assays. Membranes from chicken cerebellum and spleen specifically bound N-terminally iodinated APP, while those from gastrointestinal tissues including pancreas, mucosal and muscle layers of duodenum and proventriculus did not. Cerebral cortex membranes also failed to specifically bind Bolton-Hunter labeled 125I-APP. Liver membranes, which previously were shown to bind C-terminally iodinated APP with low affinity, also did not specifically bind N-terminally labeled preparations. It is concluded that the inability of membranes from gastrointestinal tissues and brain regions other than cerebellum to bind 125I-APP is not an artifact of location of iodine placement on the molecule and that both the N- and C-termini may be important for receptor binding. It is also concluded that liver APP binding sites may be structurally distinct from those in the cerebellum, and that gastrointestinal tissues may not be direct targets for APP action.