dibutyryl-cyclic-gmp and cholecystokinin-(27-33)

The biological activity of bovine pancreatic polypeptide (BPP) on rat exocrine pancreatic secretion was compared in vivo and in vitro. In anesthetized rats prepared with a bile-pancreatic duct cannula, BPP inhibited cholecystokinin (CCK)-stimulated (10 IDU . kg-1 X h-1) protein secretion in a dose-related manner (P less than 0.001). CCK, from 5-20 IDU . kg-1 X h-1, did not alter the degree of inhibition by BPP at 40 micrograms . kg-1 X h-1, suggesting a nonsurmountable inhibition. Analogues of BPP, including rat pancreatic polypeptide, neuropeptide Y, peptide YY, and the C-terminal hexapeptide of PP, also inhibited CCK-stimulated protein secretion. To determine whether BPP acts directly on acinar cells to suppress enzyme secretion, in vitro studies were performed. BPP and its analogues did not suppress octapeptide of CCK (CCK-8)-stimulated amylase release from either isolated rat pancreatic acini or preparations of pancreatic lobules. Specific binding of 125I-BPP to pancreatic acini was also not observed. From our data we conclude that BPP acts to inhibit pancreatic enzyme secretion in the rat in a noncompetitive manner. Absence of an effect by BPP or its analogues in vitro coupled with an absence of 125I-BPP binding to acini suggest that the inhibitory action of PP on exocrine pancreatic function is mediated by indirect mechanisms.

Topics: Amylases; Animals; Bile; Dibutyryl Cyclic GMP; Dose-Response Relationship, Drug; In Vitro Techniques; Male; Nerve Tissue Proteins; Neuropeptide Y; Pancreas; Pancreatic Polypeptide; Peptide Fragments; Peptide YY; Peptides; Proteins; Rats; Rats, Inbred Strains; Sincalide; Stimulation, Chemical

We tested the synthetic C-terminal heptapeptide of cholecystokinin, which has the same biologic activity as cholecystokinin, and various synthetic analogs of the C-terminal heptapeptide for their abilities to increase amylase secretion from dispersed acini prepared from guinea-pig pancreas. We found that altering the chemical character of the amino acid in position 27 altered the potency with which the peptide stimulated amylase secretion but did not alter the efficacy of the peptide. We also found that, in the amino acid in position 27, the major function of the side-chain seems to be to position to the sulfate ester group at a proper distance from the backbone of the peptide chain, whereas the chemical structure of the side-chain per se seems to be of relatively minor importance.

Topics: Amino Acid Sequence; Amylases; Animals; Cholecystokinin; Dibutyryl Cyclic GMP; Guinea Pigs; Male; Pancreas; Peptide Fragments; Sincalide