Somatostatin 28 interacts with CCK receptor in brain and pancreas

The ability of somatostatin analogs to interact with the binding of cholecystokinin has been studied in pancreatic and brain cortical membranes. Only the 28 amino-acid forms of somatostatin (S 28), [Nle 8]S 28 and [Des Lys 14, DTrp 22]S 28 were found to inhibit the binding of cholecystokinin to rat pancreatic plasma membranes and to increase the amylase release from pancreatic acini. This effect was independent of somatostatin receptor and resulted from an interaction between S 28 and CCK receptor. This interaction was not observed with [Leu 8, DTrp 22, Tyr 25]S 28, indicating that this analog does not possess the biological activity of the native peptide and that the iodinated peptide could not label specific S 28 receptors. S 28 interacted also with CCK receptors in cortical brain membranes. Our results support the concept that S 28, but not S 14, may function as a regulatory molecule at CCK receptors and emphasize that S 28 and S 14 may be distinct neuromodulators.