Interaction of secretin 5–27 and its analogues with hormone receptors on pancreatic acini

Abstract

The C-terminal tricosapeptide of secretin (S 5–27) and two analogues, one with asparagine replacing aspartic acid in position 15 (15-Asn-S 5–27) and one with lysine replacing aspartic acid in position 15 (15-Lys-S 5–27) were tested for their abilities to interact with hormone receptors on pancreatic acinar cells. In interacting with the receptors which prefer vasoactive intestinal peptide (vaso-active intestinal peptide-preferring receptors), the apparent affinity of 15-Asn-S 5–27 was equal to that of 15-Lys-S 5–27 and was greater than that of S 5–27. In interacting with secretin-preferring receptors, the apparent affinity of 15-Asn-S 5–27 was equal to that of S 5–27 and was greater than that of 15-Lys-S 5–27. In interacting with the secretin-preferring receptors each of the secretin fragments was approximately 2% as effective as secretin in causing an increase in cellular cyclic AMP. None of these fragments was able to cause a detectable increase in cyclic AMP mediated by the vasoactive intestinal peptide-preferring receptors. The dose vs. response curves for the action of secretin and vasoactive intestinal peptide on cellular cyclic AMP and on amylase secretion as well as the patetern of effects of secretin fragments on these actions indicated that the increase in amylase secretion caused by vasoactive intestinal peptide and secretin is mediated exclusively by the vasoactive intestinal peptide-preferring receptors. Furthermore, occupation of approximately 50% of the vasoactive intestinal peptide-preferring receptors is sufficient to cause maximal stimulation of amylase secretion.