Action of pancreatic polypeptide on rat pancreatic secretion: in vivo and in vitro

Abstract

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.

Effects of wheat bran on exocrine pancreas secretion in the pig

“…We also noted an increase in the plasma levels of PP and somatostatin, peptides known to inhibit the volume of pancreatic secretion in dogs (Konturek et al, 1982(Konturek et al, , 1985. Such an effect in pigs does not seem to be due to somatostatin ; this agrees with results obtained by Bloom, Joffe and Polak (1975) (Lin et al, 1977 ;Konturek et al, 1982 ;Louie, William and Owyang, 1985 …”

Vagal afferent pathway mediates physiological action of cholecystokinin on pancreatic enzyme secretion.

“…Pancreaticobiliary juice protein was measured spectrophotometrically using the assay method of Bradford ( 12). Our previous study ( 13) confirmed that the increase in protein output in the bile pancreatic juice after CCK-8 stimulation mainly reflected protein from the pancreatic source. Biliary juice protein did not increase with CCK stimulation.…”

Effects of human pancreatic polypeptide on exocrine pancreatic function in conscious rats.

“…No receptors for PP on the pancreatic acinar cells in the rat could be demonstrated (Louie et al 1985), and it was suggested that the indirect mechanism was involved in the action of PP (Louie et al 1985). Therefore, the mechanism of inhibitory effect of PP on pancreatic exocrine secretion is considered to be indirect.…”

“…Therefore, the mechanism of inhibitory effect of PP on pancreatic exocrine secretion is considered to be indirect. It was also reported that other inhibitory agents, such as PYY, NPY and somatostatin could not inhibit pancreatic secretion in isolated acini (Louie et al 1985;Singh 1986), although the receptor for somatostatin on acinar cells was recently defined (Strikant 1986). We have reported an experimental system for determining pancreatic exocrine secretion in conscious rats (Miyasaka and Green 1984;Miyasaka et al 1986).…”

“…The exact mechanism of the feedback regulation has not been elucidated, but it has been shown that CCK is released when protease activities are removed in the proximal intestine decreased below the threshold (Louie et al 1986). Louie et al (1985) examined the effect of PP on pancreatic secretion in the anesthetized rat and observed that 20 ,u g/kg/hr bovine PP caused the maximal inhibition of CCK stimulated pancreatic secretion and that even rat PP (40pg/ kg/hr) inhibited CCK-33 induced bile-pancreatic protein output by 20%. However, in the present experiments, as little as l ,u g/kg/hr of hPP inhibited protein output by 55% (Table 1).…”