Effect of pancreastatin on pancreatic exocrine secretion in vivo and in vitro

The effects of pancreastatin on pancreatic exocrine secretion were examined both in vivo and in vitro in rats. Pancreastatin inhibited pancreatic fluid and protein outputs stimulated by the exclusion of pancreatic juice from the intestine with the intraduodenal infusion of Trasylol but did not inhibit bicarbonate output stimulated by HCl in vivo in conscious rats. However, pancreastatin did not affect amylase release from dispersed acini or Ca concentration in acinar cells. Therefore, it is concluded that pancreastatin inhibits pancreatic exocrine secretion but the effect is indirect.     

Effects of porcine pancreastatin on postprandial pancreatic exocrine secretion and endocrine functions in the conscious rat

The inhibitory effect of a newly discovered polypeptide, pancreastatin, on postprandial pancreatic exocrine secretions and endocrine functions was examined in the conscious rat with a chronic external bile, pancreatic and gastric fistula. The infusion of 100 and 200 pmol/kg/h of pancreastatin significantly inhibited meal-stimulated pancreatic secretion of fluid and protein but not bicarbonate in a dose-dependent manner. The infusion of 100 and 200 pmol/kg/h of pancreastatin increased plasma pancreastatin concentrations (mean +/- SE) up to 133.5 +/- 15.9 and 209.8 +/- 14.5 pM, respectively. However, the same doses of pancreastatin failed to inhibit postprandial insulin and gastrin releases and did not affect blood glucose levels. It is suggested that pancreastatin may be an inhibitor of postprandial pancreatic exocrine secretion. However, the doses used in the present study may not have been high enough to affect endocrine functions.     

Effect of pancreastatin on cerulein-stimulated pancreatic blood flow and exocrine secretion in anaesthetized rats

BACKGROUND: Pancreastatin (PST) is an inhibitor of pancreatic exocrine secretion in vivo but not in vitro, which suggests that the inhibitory effect of PST is indirect, that is, not mediated by a specific receptor on pancreatic acinar cells. In this study, we investigated the effects of PST on pancreatic exocrine secretion and local pancreatic blood flow in anaesthetized rats to elucidate the participation of PST in indirect regulation of pancreatic exocrine function through blood supply. METHODS: Pancreastatin (100, 200 or 500 pmol/kg per h) was administered intravenously under background infusion of cerulein (0.5 microg/kg per h), a cholecystokinin analogue. Pancreatic exocrine secretion was monitored by volume and protein output of the pancreatic juice and local pancreatic blood flow was measured by the hydrogen gas clearance method. RESULTS: Pancreastatin significantly reduced cerulein-induced local pancreatic blood flow in a dose-dependent manner. Pancreatic exocrine secretion was also reduced significantly by PST dose-dependently. Pancreastatin did not change systemic blood pressure.These results suggested that the reduction of pancreatic blood flow is associated with the reduction of pancreatic exocrine secretion. CONCLUSIONS: We conclude that the mechanism of PST-induced inhibition of pancreatic exocrine secretion is, at least, partly mediated by the reduction of local pancreatic blood flow through blockade, caused by the action of cerulein on pancreatic blood flow.     

Effect of pancreastatin on insulin secretion and the exocrine pancreas in rats]

Pancreastatin, a 49-amino-acid C-terminal amidated peptide, was isolated from porcine pancreas in 1986. It has been reported to inhibit insulin release and exocrine pancreatic secretion, but both these effects have been disputed. In the isolated perfused rat pancreas we therefore studied the effect of pancreastatin on insulin and exocrine pancreatic secretion. Neither basal exocrine pancreatic secretion, nor exocrine secretion stimulated by CCK-8, bombesin or secretin were affected by pancreastatin. 20 or 200 pM pancreastatin, however, significantly inhibited stimulated insulin release. We conclude that pancreastatin seems to be yet another inhibitory peptide, which--for unknown reasons--inhibits insulin release both in vivo and in vitro, but exocrine pancreatic secretion only in vivo.     

Effect of tetramethylpyrazine on exocrine pancreatic and bile secretion

AIM: To investigate the effect of tetramethylpyrazine ?A (ligustrazine, TMP) on the secretion of exocrine pancreas(and biliary). METHODS: In in vivo study, we investigated the effect of TMP on the secretion of pancreatic-bile juice (PBJ) in rats. Using human pancreatic duct cell line, CAPAN-1, combined with the short-circuit current (Isc) technique we further studied the effect of TMP on the pancreatic anion secretion. RESULTS: Administration of TMP (80mg/kg, ip) significantly increased the secretion of PBJ (P<0.05), but the pH of PBJ and the secretion of pancreatic protein were not significantly affected. Basolateral addition of TMP produced a dosedependent increase in Isc(EC50=1.56mmol/L), which contained a fast transient Isc response followed by a slow decay. Apical application of CI- channel blockers, DPC (1mmol/L), decreased the response by about 67.1% (P<0.001), whereasamiloride (100μmol/L), a epithelial sodium channel blockers, had no effect. Removal of extracellular HCO3^- abolished TMP-induced increase in Isc by about 74.4% (P<0.001),but the removal of external Cl^- did not. Pretreatment with phosphodiesterase inhibitor, IBMX(0.5mmol/L), decreasedthe TMP-induced Isc by 91% (P<0.001). CONCLUSION: TMP could stimulate the secretion of PBJ, especially pancreatic ductal HCO3- secretion via cAMP or cGMP-dependent pathway. It need further study to investigate the roles of cAMP or cGMP in the effect of TMP on the secretion of exocrine pancreas.     

Effect of nicotine on serum secretin and exocrine pancreatic secretion

The effect of nicotine (100 g/kg hr^–1) on serum secretin and pancreatic secretions was studied in dogs with chronic pancreatic fistulas. Release of immunoreactive secretin (IRS) was stimulated by intraduodenal infusion of HCl (9.6 mEq/30 min). Pancreatic flow rate and bicarbonate and protein secretions were stimulated either by intestinal acidification or infusion of exogenous secretin (1.0 IU/kg hr^–1). It was found that nicotine delayed the appearance of peak IRS concentrations in response to intraduodenal HCl by about 20 min. However, nicotine had no effect on the total amount of IRS released nor was this delay accompanied by a similar delay in the appearance of peak bicarbonate output. Furthermore, nicotine did not affect pancreatic secretory function stimulated by either HCl or exogenous secretin. These data do not support the thesis that nicotine plays an important role in the pathogenesis of duodenal ulcers in smokers by inhibiting the pancreatic secretion of bicarbonate.     

Effects of L-364,718 on pancreatic exocrine and endocrine secretion in the rat.

We examined the inhibitory effect of L-364,718, a nonpeptide cholecystokinin (CCK) antagonist, on CCK stimulation of pancreatic exocrine and endocrine secretion in both the isolated pancreatic acini and the isolated perfused pancreata of rats. In the isolated acini, L-364,718 inhibited CCK octapeptide (CCK-8)-stimulated amylase release and binding of 125I-CCK-8 in a dose-dependent manner without appreciable effects on the basal amylase secretion. L-364,718 also inhibited amylase release in response to caerulein and gastrin I, but had no effect on amylase release stimulated by other secretagogues or by agents bypassing receptors. Similarly, binding of N-methylscopolamine to pancreatic acini was not inhibited by L-364,718. In the isolated perfused pancreata, L-364,718 inhibited CCK-8-stimulated pancreatic exocrine secretion and insulin release. The inhibitory effects of L-364,718 were more potent for insulin release than for exocrine secretion and persisted even after the removal of L-364,718 infusion. These results clearly demonstrate that L-364,718 is a specific, potent, and prolonged antagonist of CCK's stimulatory actions on pancreatic acinar and B cells.     

Effect of caerulein on pancreatic endocrine and exocrine secretion from the perfused rat pancreas (author's transl)]

Several investigations in vivo and in vitro have shown that gastro-intestinal hormones stimulate insulin secretion. However, the reports on the insulinotropic activity of pancreozymin are contradictory. The conflicting results are probably due to the fact that pure native preparation of this hormone has not been obtained in "physiologic" doses. In the present study this problem has been investigated by exposing rat pancreas to caerulein in vitro. Caerulein, an active decapeptide isolated from the skin of the Australian amphibia Hyla caerulea, resembles pancreozymin in chemical structure, including C-terminus. This active polypeptide of nonmammalian origin has been shown to possess all the biological activities of pancreozymin. The present investigation was undertaken to evaluate the significance of the interactions of exocrine and endocrine pancreas using perfused rat pancreas in vitro. Biphasic insulin release was demonstrated with caerulein at concentrations higher than 1 ng/ml. Insulin response of the first phase was proportional to the dose up to 1 microgram/ml. The second phase of insulin release was, however, almost constant, regardless of the concentrations of caerulein. Release of glucagon was stimulated by the same concentrations of caerulein which stimulated insulin release. Maximal response of the pancreatic amylase and pancretic juice output were observed with 1 ng/ml of caerulein. With higher doses, significantly less secretory responses were observed. The dissociation of the response to caerulein between endocrine and exocrine pancreas was found.     

Involvement of endogenous prostaglandins in pancreatic endocrine and exocrine secretion in dog pancreas

The involvement of endogenous prostaglandins (PGs) in pancreatic endocrine and exocrine secretion was investigated, using the isolated and perfused dog pancreas. Spontaneous production of both PGE2 and 6-keto-PGF1 alpha was recorded in venous effluent. Prostaglandin production increased following stimulation with both 10 x 10(-11) and 20 x 10(-11) mol of CCK-8, but was not affected by a 5 x 10(-11) mol infusion. Insulin, glucagon, and amylase release was stimulated by 10 x 10(-11) mol of CCK-8. Indomethacin pretreatment with 10 mg/kg totally abolished endogenous PG production, but failed to suppress an insulin and glucagon response. On the other hand, an amylase response was accelerated by indomethacin pretreatment. Although low dose CCK-8 failed to stimulate endogenous prostaglandin production, a brisk exocrine secretion was not suppressed by indomethacin pretreatment. From the above results, we conclude that endogenous PGs do not appear to play an important role in pancreatic endocrine and exocrine secretion, but might have a cytoprotective effect on the pancreatic acinar cells damaged by CCK-8.     

Effect of acarbose on exocrine and endocrine pancreatic function in the rat

Exocrine and endocrine pancreatic function were studied simultaneously in the isolated perfused pancreas from rats fed a normal or an acarbose-containing diet (150 mg/100 g food) for 20 days. Body weight gain of acarbose-treated rats was slightly lower than that of control rats, despite a larger food intake. Basal and caerulein-stimulated flow rates of pancreatic juice from acarbose-treated rat pancreases were similar to those from controls, suggesting that the treated rat pancreas has normal sensitivity and responsiveness to caerulein. On the other hand, amylase output in response to caerulein was significantly decreased in acarbose-treated rat pancreases, though basal output was normal. The addition of acarbose to the diet for 20 days had no effect on the speed of the insulin response to glucose and caerulein, but the magnitude of insulin secretion to glucose stimulation was reduced by 40% and the caerulein-induced additional output of insulin by 30% in the treated group as compared with the control group. The present investigation has demonstrated that inhibition of key enzymes for carbohydrate digestion decreases not only the secretory responsiveness of amylase from acinar cells to caerulein stimulation but also the sensitivity of the insulin-secretory mechanism of pancreatic B cells to glucose and non-glucose stimulation.     

Effect of ethanol on pancreatic exocrine secretion in rats.

The effect of ethanol on pancreatic exocrine secretion was studied in isolated rat pancreatic acini. Ethanol caused a dose-dependent stimulation of amylase release, and a twofold increase of amylase release was observed with 600 mM ethanol. Ethanol inhibited cholecystokinin octapeptide (CCK-8)- and carbamylcholine-stimulated amylase release and similarly inhibited binding of [125I]CCK-8 and [N-methyl-3H]scopolamine to isolated rat pancreatic acini in a dose-dependent manner. The inhibitory effect of ethanol was fully reversible with respect to CCK-8-induced amylase release. On the other hand, ethanol potentiated secretin- and vasoactive intestinal peptide (VIP)-stimulated amylase release. Ethanol induced a small but significant increase in Ca2+ efflux, whereas CCK-8 induced an immediate and large increase, but ethanol significantly inhibited CCK-8-stimulated Ca2+ efflux. The present study clearly demonstrates the dual effects of ethanol on pancreatic exocrine function: stimulation and inhibition. We suggest that mobilization of intracellular Ca2+ may be involved in the mechanism of ethanol's action on isolated rat pancreatic acini.     

Effect of parenteral amino acids on human pancreatic exocrine secretion

Parenteral administration of amino acids has been utilized for the nutritional support of patients with a variety of gastrointestinal disorders including protracted pancreatitis and pancreatic fistulae. However, the effect of parenteral amino acid administration alone on human pancreatic secretion has not been studied. We have studied the short-term effect of parenteral administration of amino acids on pancreatic exocrine secretion in seven healthy men. A double-lumen tube was placed in the duodenum and polyethylene glycol was perfused into the proximal duodenum at the rate of 10 ml/min. A second double-lumen tube was placed in the stomach and bromsulfthalein was perfused into the cardia. Samples of duodenal contents were aspirated and gastric contents recovered during one hour of intravenous saline infusion followed by two hours of an amino acid mixture infusion. Hourly outputs of protein and pancreatic enzymes were determined, correcting for duodenogastric reflux based on concentrations of both markers in the samples. Despite an average increase of 72% in the plasma concentration of the infused amino acids, the outputs of protein, trypsin and amylase did not change significantly during amino acid infusion; the output of lipase decreased significantly during amino acid infusion. Two subjects were given intravenous secretin and cholecystokinin following amino acids; this resulted in increased outputs of protein, trypsin, and amylase in both. We conclude that the parenteral administration of amino acids to healthy young men does not stimulate pancreatic enzyme secretion as measured by the method using duodenal marker perfusion at the rate of 10 ml/min.This research was supported by a grant from U.S. Veterans Administration.