The effect of oleate on pancreatic and bile secretion in the conscious rat

The effects of sodium oleate infused into either the duodenum or the terminal ileum on bile and pancreatic secretion were examined in the conscious rat. Rats were prepared with cannulae draining pure bile and pancreatic juice separately, and with an ileal and two duodenal cannulae. A 40 mM taurocholate solution containing 7 mg/ml bovine trypsin was infused into the duodenum throughout the experiment to replace diverted bile-pancreatic juice to maintain the normal regulation of pancreatic secretion. The intraduodenal infusion of sodium oleate significantly increased pancreatic juice flow, protein, and bicarbonate outputs, whereas it did not affect bile secretion. Intravenous infusion of proglumide (300 mg/kg/hr) did not inhibit pancreatic secretion stimulated by intraduodenal infusion of sodium oleate. An intravenous infusion of atropine (100 micrograms/kg/hr) attenuated protein and fluid secretions but not that of bicarbonate in response to intraduodenal oleate. In contrast, the intraileal infusion of oleate had no effect on pancreatic secretion, whereas it decreased bile flow, bicarbonate, and bile salt outputs. In conclusion, sodium oleate introduced in the duodenum stimulates pancreatic secretion but oleate in the terminal ileum inhibits bile secretion.     

Effect of acute hyperglycemia on basal, secretin and secretin + cholecystokinin stimulated exocrine pancreatic secretion in humans

Pancreatico-biliary secretion is reduced during acute hyperglycemia. We investigated whether alterations in pancreatico-biliary flow or volume output are responsible for the observed reduction in duodenal output of pancreatic enzymes and bilirubin during hyperglycemia. Eight healthy subjects were studied on two occasions during normoglycemia and hyperglycemia (15 mmol/l). Pancreatico-biliary output was measured by aspiration using a recovery marker under basal conditions (60 min), during secretin infusion (0.1 CU/kg.h) for 60 min and during secretin + CCK (0.5 IDU/kg.h) infusion for 60 min. Secretin was infused to stimulate pancreatico-biliary flow and volume output. Secretin significantly (P<0.005-P<0.05) increased volume and bicarbonate output and CCK significantly (P<0.01) increased the output of bilirubin, pancreatic enzymes, bicarbonate and volume, both during normoglycemia and hyperglycemia. During hyperglycemia basal, secretin stimulated and secretin + CCK stimulated total pancreatico-biliary output were significantly (P<0.005-P<0.05) reduced compared to normoglycemia. The incremental outputs, however, were not significantly different between hyper- and normoglycemia. Pancreatic volume output was significantly (P<0.05) reduced during hyperglycemia compared to normoglycemia under basal conditions (31+/-16 m/h versus 132+/-33 m/h) during secretin infusion (130+/-17 ml/h versus 200+/-34 m/h) and during secretin + CCK infusion (370+/-39 ml/h versus 573+/-82 ml/h). Plasma PP levels were significantly (P<0.05) reduced during hyperglycemia. It is concluded that 1) hyperglycemia significantly reduces basal pancreatico-biliary output 2) the incremental pancreaticobiliary output in response to secretin or secretin + CCK infusion is not significantly affected during hyperglycemia, 3) a reduction in volume output contributes to the inhibitory effect of hyperglycemia on pancreatico-biliary secretion, 4) hyperglycemia reduces PP secretion suggesting vagal-cholinergic inhibition of pancreatico-biliary secretion and volume during hyperglycemia.     

促胰液素和胆囊收缩素族激素对豚鼠肝胆汁分泌的影响

用具备胃瘘和胆瘘的豚鼠于人工维持胆汁酸池恒定的条件下,观察促胰液素(SEC)和胆囊收缩素(CCK)族激素[包括雨蛙肽(CAE)、五肽胃泌素(G5)和内源性CCK]对肝胆汁分泌的影响及其相互作用。结果表明:静脉灌注SEC、CAE或肠内灌注左旋苯丙氨酸(L-PHE,促内源性CCK释放剂)后,胆汁流量、胆汁HCO~-_3和Cl~-排出量均显著增多,并呈剂量-效应关系,但静脉注射G5则无利胆效应。在恒速灌注SEC的背景下,CAE或CCK对胆汁HCO~-_3排出的效应分别大于它们单独给予时的效应(P<0.05或P<0.01)。这些激素对胆汁酸的排出量均无影响。上述结果表明,SEC,CAE和内源性CCK均有利胆作用,所刺激的肝胆汁属于不依赖胆汁酸部分。G5则无利胆效应。对胆汁中HCO~-_3的排出,SEC与CAE或内源性CCK间有相互加强作用。     

Hepatic bile and pancreatic exocrine secretions evoked by gastrointestinal peptides in sheep

The secretory response of hepatic bile and exocrine pancreas to gastrointestinal peptides has been studied in chronically cannulated sheep. Pancreatic juice flow and protein output were evoked dose dependently by intraportal injection of secretin, CCK-8, caerulein, VIP and neurotensin. However, biliary secretion was evoked by only secretin. Biliary and pancreatic exocrine secretions were enhanced by delivered gastric juice into the duodenum as followed by the increased plasma concentration of immunoreactive secretin (IRS). Results suggest that secretin is the major peptide that regulates pancreatic exocrine secretion and hepatic bile production in the sheep.     

Relationship between intravenous ethanol, alcohol-induced inhibition of pancreatic secretion and plasma concentration of immunoreactive pancreatic polypeptide, vasoactive intestinal peptide, and somatostatin in man

We have studied in seven men, consuming less than 50 g alcohol daily, the effect of intravenous (i.v.) ethanol on (a) hormonally (secretin + CCK PZ) submaximally stimulated pancreatic secretion and (b) blood levels of pancreatic polypeptide (PP), vasoactive intestinal peptide (VIP) and somatostatin. After intravenous ethanol (600 mg/kg), pancreatic secretion decreased in all subjects and plasma levels of PP and VIP increased significantly. Moreover, there was a significant correlation between the mean inhibition of chymotrypsin output and the mean increase in PP plasma levels during the first 45 min following ethanol infusion. Therefore i.v. infusion of alcohol elicits release of PP and VIP and PP release could explain in part at least the alcohol-induced pancreatic inhibition observed in non-alcoholic men.     

Interactions between bile and pancreatic juice diversions on cholecystokinin release and pancreas in conscious rats

Pancreatic exocrine secretion in the conscious rat is regulated by proteases secreted by the pancreas, and cholecystokinin (CCK) is known to be involved in its mechanism. It has also been reported that the absence of either pancreatic juice or bile in the duodenum could stimulate pancreatic secretion. Therefore, differences in CCK release responding to the exclusion of bile, pancreatic juice (PJ), or both bile and pancreatic juice (BPJ) from the intestine were examined by using a bioassay for cholecystokinin. Plasma CCK levels were increased by all three treatments compared with the basal value, the order of their effects being BPJ greater than PJ greater than bile diversion, and CCK concentrations produced by BPJ diversion were much greater than can be explained as simply summed effect of exclusions of bile and PJ. Pancreatic exocrine secretions were significantly increased by PJ and BPJ diversions, but the effect of bile diversion on the pancreas was not statistically significant. An additional infusion of CR-1409 (0.1 mg/rat), one of CCK receptor antagonists, inhibited exocrine function stimulated by BPJ diversion. We conclude (i) BPJ diversion is the strongest endogenous stimulant on CCK release; (ii) the potentiation between bile and PJ diversions is induced on CCK release; (iii) pancreatic protein secretion during BPJ diversion is mainly modulated by CCK.     

CCK and PYY do not participate in the delayed inhibition of pancreatic secretion, after stimulation by duodenal oleic acid infusion.

The role played by CCK in the stimulation of pancreatic secretion by duodenal infusion of oleic acid in conscious rats was studied using a potent and specific CCK receptor antagonist. CR-1409 did not alter basal secretion, which does not require CCK. The three doses of CR-1409 that were used (2, 4 and 8 mg/kg/h) suppressed the protein response to duodenal infusion of oleic acid and significantly enhanced the delayed inhibition normally observed in control rats (-81%, -87% and -88% vs. -51% of basal in controls). CR-1409 dose-dependently reduced the volume of pancreatic secretion after duodenal infusion of oleic acid (0.40 +/- 0.02, 0.36 +/- 0.02, 0.34 +/- 0.03 vs. 0.48 +/- 0.04 ml/30 min for 2, 4, 8 mg/kg/h and controls, respectively) and revealed a delayed inhibition of volume and a slight reduction of bicarbonate secretion. CCK appears to be directly responsible for the protein and also water response to duodenal infusion of oleic acid, and to be indirectly involved in bicarbonate stimulation. PYY antiserum significantly augmented protein output after duodenal infusion of oleic acid (10.75 +/- 1.40, 14.10 +/- 1.60 vs. 8.60 +/- 1.20 mg/30 min, 1 microliter, 2 microliters and controls), but failed to modify the delayed inhibition: PYY modulates the response to duodenal infusion of oleic acid and is not involved in the delayed inhibition, which was shown to be also present for volume, but which is normally masked by the action of CCK.     

Effects of pancreatic polypeptide on biliary flow and bile acid secretion stimulated by secretin and cholecystokinin in the conscious pig

Fourteen castrated male Large White pigs, weighing 42.5 +/- 1.0 kg, were fitted with biliary and duodenal fistulae for biliary secretion studies. Furthermore, catheters were placed in a carotid artery for blood sampling and in a jugular vein for peptide infusion. Bile was automatically restituted to the animals and continuously sampled for analysis on experimental days. Following an 8 day recovery period, infusion studies were performed after an overnight fast. After a 30 min basal period, sustained biliary flow and bile acid output were obtained and maintained throughout the assay with secretin (36 pmol/kg/h) and CCK-8 (600 pmol/kg/h) infusion. Then, 200, 400, 600, 800 or 1200 pmol/kg/h of porcine pancreatic polypeptide (PP) were infused for 60 min. Secretin plus CCK infusion was continued for 1 h after PP infusion was stopped. Each dose of PP was given on a separate day. Biliary flow was not affected by PP except for the dose of 400 pmol/kg/h. On the contrary, bile acid concentration and output decreased with the lowest dose of PP (200 pmol/kg/h). As soon as the first dose of PP was infused, bile acid concentration and output fell to about 60% of values obtained with secretin plus CCK. Plasma levels of PP were below or similar to postprandial values for 200, 400 and 600 pmol/kg/h and they were significantly larger with 800 and 1200 pmol/kg/h. Bile acid concentration and output did not return to values obtained with secretin plus CCK infusion after cessation of PP infusion. In conclusion, porcine PP given in physiological doses to the pig decreases bile acid output whereas biliary flow remains unaffected.     

Mutual dependence of VIP/PACAP and CCK receptor signaling for a physiological role in duck exocrine pancreatic secretion

Unlike in rodents, CCK has not been established as a physiological regulator in avian exocrine pancreatic secretion. In the isolated duck pancreatic acini, 1 nM CCK was required for stimulation of amylase secretion, maximal effect being achieved at 10 nM; picomolar CCK was without effect. Vasoactive intestinal peptide (VIP)/pituitary adenylate cyclase activating peptide (PACAP) receptor (VPAC) agonists PACAP-38 and PACAP-27 (10(-12)-10(-7) M) alone had no effect, but made picomolar CCK effective. VPAC agonist VIP 10(-10)-10(-7) M stimulated amylase secretion marginally, but made CCK 10(-12)-10(-10) M effective also. PACAP-27 and VIP both shifted the maximal CCK concentration from 10(-8) to 10(-9) M. This sensitizing effect was mimicked by forskolin. CCK dose dependently induced intracellular Ca2+ concentration ([Ca2+]i) oscillations. PACAP-38 (1 nM), PACAP-27 (1 nM), VIP (10 nM), or forskolin (10 microM) alone did not stimulate [Ca2+]i increase, neither did they modulate CCK (1 nM)-induced oscillations; but when they were added to cells simultaneously exposed to subthreshold CCK (10 pM), calcium spikes emerged. Amylase secretion induced by the simultaneous presence of 10 pM CCK and VPAC agonists was completely blocked by removing extracellular calcium, but the protein kinase C inhibitor staurosporine (1 microM) was without effect. CCK (10 nM)-induced secretion was inhibited by CCK1 receptor antagonist FK480 (1 microM). Gastrin from 10(-12) to 10(-6) M did not stimulate amylase secretion nor did it (100 nM) induce [Ca2+]i increase. The above data suggest that duck pancreatic acini possess both CCK1 and VPAC receptors; simultaneous activation of both is required for each to play a physiological role.     

Effects of pancreatic polypeptide on the pancreatic exocrine secretion stimulated by secretin and cholecystokinin in the conscious pig

Fourteen castrated male Large White pigs, weighing 42.5 +/- 1.0 kg, were fitted with pancreatic and duodenal fistulae for pancreatic secretion studies. Moreover, catheters were placed in a carotid artery for blood sampling and in a jugular vein for peptide infusion. Pancreatic juice was automatically restituted to the animals and continuously sampled for analysis on experimental days. Following an 8-day recovery period, perfusion studies were performed after an overnight fast. After a 30-min basal period, sustained pancreatic flow and protein output were obtained and maintained throughout the assay with secretin (36 pmol/kg/h) and CCK-8 (600 pmol/kg/h) infusion. Then, 200, 400, 600, 800 or 1200 pmol/kg/h of porcine pancreatic polypeptide (PP) were infused for 60 min. Secretin + CCK infusion was continued for 1 h after PP infusion was stopped. Each dose of PP was given on a separate day. Neither pancreatic flow nor bicarbonate output were affected whatever the dose of infused PP. On the contrary, protein concentration and output decreased with the lowest dose of PP (200 pmol/kg/h) and the diminution was more pronounced with the other doses. With 600 pmol/kg/h as well as with 800 and 1200 pmol/kg/h of PP, pancreatic protein output fell to about 20% of values obtained with secretin + CCK. Plasma levels of PP were below or similar to postprandial values for 200, 400 and 600 pmol/kg/h and they were significantly larger with 800 and 1200 pmol/kg/h. Protein concentration and output returned to values obtained with secretin + CCK infusion after cessation of PP infusion. In conclusion, porcine PP given in physiological doses to the pig decreases pancreatic protein output whereas pancreatic flow remains unaffected.     

Neurotensin modulates the composition of pancreatic exocrine secretions in chickens

The effects of neurotensin on pancreatic exocrine secretion were examined in fasted, conscious White Leghorn hens. A cannula was surgically implanted in the central duct serving the ventral lobe of the pancreas in order to collect pure pancreatic juice. Following recovery, neurotensin was infused intravenously at 3.6 or 10.8 pmol/kg*min. The volume and pH of the pancreatic secretions were recorded and total pancreatic protein concentration, amylase, lipase, trypsin, and chymotrypsin activity were measured every 30 min for 2 hr and compared to secretions following the infusion of 0.9% saline. Our results demonstrated that neurotensin did not affect the pH nor the pancreatic juice protein concentration, but did increase secretion rate following neurotensin infusion at 3.6 pmol/kg*min. Amylase activity was significantly depressed during neurotensin infusions, while lipase (both pancreatic and carboxylester lipase) activity was significantly elevated. The ratio of amylase to lipase activity was especially depressed by neurotensin infusion at 10.8 pmol/kg*min. Insufficient secretory activity prevented a balanced statistical analysis of chymotrypsin activity, but from a pooled analysis, neurotensin had no effect on protease activity in the pancreatic juice. These results support our current research indicating that neurotensin may be a hormonal regulator of postprandial lipid digestion in chickens.     

Effect of intraduodenal sodium bicarbonate in rat and rabbit exocrine pancreatic secretion.

The effect of intraduodenal sodium bicarbonate, 0.1 M, on exocrine pancreatic secretion and the release of two peptides, secretin and VIP, was studied in anesthetized rats and rabbits, two species largely used in the gastroenterology laboratories. In the rabbit, intraduodenal sodium bicarbonate perfusion had no effect either on exocrine pancreatic secretion or on portal plasma levels of secretin and VIP. By contrast, in the rat, intraduodenal sodium bicarbonate perfusion significantly increased hydroelectrolyte exocrine pancreatic secretion and portal plasma secretin levels. A clear interspecific difference reflecting the different gastrointestinal physiology of both species is observed.     

Exocrine secretion of epidermal growth factor from Brunner's glands. Stimulation by VIP and acetylcholine

Brunner's glands of the duodenum are innervated by cholinergic and VIP-ergic nerves, and the glands have been shown to contain epidermal growth factor (EGF). In this study the effect of VIP and acetylcholine (Ach) on secretion of EGF from Brunner's glands was investigated in the rat. Intravenous infusion of VIP stimulated the flow rate of duodenal secretion, an effect which was inhibited by atropine. Ach alone did not significantly increase flow rate, and combined infusion of VIP and Ach induced the same flow as VIP alone. Concentration of EGF in duodenal secretion was increased by infusion of Ach, and this effect was potentiated by VIP. Infusion of VIP alone did not influence EGF concentration. EGF output from Brunner's glands was significantly stimulated by i.v. infusion of VIP and of Ach and combined infusion further increased EGF output. The study has demonstrated exocrine secretion of EGF from Brunner's glands, and it is suggested that stimulation is mediated by interaction of neuronal VIP and Ach.     

Effect of immunoneutralisation of cholecystokinin on bombesin-stimulated pancreatic enzyme secretion in the rat

Infusion of bombesin stimulates plasma cholecystokinin (CCK) and pancreatic enzyme secretion in various species, including the rat. This study was undertaken in two groups of four conscious rats with a cannulated pancreatic duct to determine the role of endogenously released CCK in mediating the effect of bombesin on pancreatic enzyme secretion. Infusion of 2 ml CCK antiserum or normal rabbit serum for 40 min was followed 10 min later by infusion of 18 pmol/kg bombesin for 30 min and after an interval of 90 min by infusion of 24 pmol/kg CCK for 30 min. After administration of control rabbit serum, pancreatic protein secretion increased by 3.2 +/- 1.0 mg/30 min during bombesin and 4.0 +/- 1.5 mg/30 min during CCK, while the plasma CCK increments were 1.7 +/- 0.5 pM and 7.0 +/- 0.9 pM for the bombesin and CCK infusions, respectively. Immunoneutralisation with the CCK antiserum did not significantly affect bombesin-stimulated pancreatic protein secretion (3.6 +/- 1.3 mg/30 min), but almost abolished the pancreatic protein response to CCK (0.5 +/- 0.2 mg/30 min). It is therefore concluded that CCK is not an important mediator of the stimulatory effect of bombesin on the pancreas in the rat.     

Immunoreactive cholecystokinin in human and rat plasma: correlation of pancreatic secretion in response to CCK

Immunoreactive cholecystokinin (CCK) levels in human and rat plasma are described using a radioimmunoassay specific for the biologically active sulfated end of CCK. This assay detected significant changes in plasma cholecystokinin levels during intrajejunal administration of amino acids and intravenous infusions of CCK-8 which were followed by increased pancreatic secretion. In humans, the concentration (pg/ml) of plasma cholecystokinin increased from 10.8 to 18.9 following intrajejunal amino acid instillation and from 15.4 to 31.1 during CCK infusion, while pancreatic trypsin secretion increased more than 15 fold. Ingestion of a test meal also caused a rapid and significant elevation (P less than 0.05) in both plasma CCK (14.5-21.7 pg/ml) and gastrin (50-160 pg/ml) levels. In the rat, an injection of 46 ng of CCK-8 produced a 300% increase in immunoreactive plasma CCK levels (2 min) and caused peak pancreatic protein secretion within 5 min; 4 fold lower doses (11.5 ng) elevated plasma CCK by 38% and pancreatic protein secretion to a small but significant extent. The ability of this assay to detect various forms of sulfated CCK in human plasma was also determined. Following gel chromatography on Sephadex G-50, at least three different immunoreactive peaks were found in plasma from fasted subjects and after intrajejunal amino acid stimulation. While the lower molecular weight CCK peptides (CCK-8 and CCK-12) were detected in plasma from both fasted and stimulated subjects, the larger form (CCK-33) was only present in measurable concentrations after amino acid infusion. The simultaneous measurement of increased plasma CCK levels and pancreatic secretion and the changes in the distribution of CCK peptides following amino acid infusion provides strong support that this assay detects physiologically relevant changes in biologically active CCK peptides.     

Effects of cholecystokinin octapeptide on the pancreatic exocrine secretion in the pig

In conscious pigs, intravenous infusion of serial doses of cholecystokinin octapeptide (CCK8; 2.9-232.3 pmol.kg-1.min-1) upon a background of secretin resulted in a linear increase of plasma CCK-like immunoreactivity (CCK-LI) concentration and evoked a dose-related increase of pancreatic volume and bicarbonate and protein outputs. The threshold plasma CCK-LI concentration for significant pancreatic response was 103.8 +/- 10.2 pM using a CCK8 dose of 8.8 pmol.kg-1.min-1. The maximum pancreatic response was observed for a plasma CCK-LI level of 498.0 +/- 15.3 pM using 77.2 pmol CCK8.kg-1.min-1. In anesthetized pigs, the threshold plasma CCK-LI concentration for pancreatic response was 1500 pM (actual CCK8 dose of 60.3 pmol.kg-1.min-1). The physiological relevance of this finding was assessed by comparing the food-induced increase of pancreatic secretion with that of plasma CCK-LI. Food ingestion was followed by a sharp pancreatic response and by a progressive increase of plasma CCK-LI to a peak increment of about 15 pM. Gel chromatography of portal and peripheral plasma from fed animals revealed three major peaks in the volumes of CCK33/39 and CCK8, and in a volume intermediate between CCK33/39 and CCK8. An additional minor component eluted ahead of CCK33/39. CCK8, which is one of the CCK components released after food intake, appears to be a fairly weak pancreatic stimulant in pigs.     

Differential mechanism and site of action of CCK on the pancreatic secretion and growth in rats

Recent studies demonstrated that cholecystokinin (CCK) at physiological levels stimulates pancreatic enzyme secretion via a capsaicin-sensitive afferent vagal pathway. This study examined whether chemical ablation of afferent vagal fibers influences pancreatic growth and secretion in rats. Bilateral subdiaphragmatic vagal trunks were exposed, and capsaicin solution was applied. Pancreatic wet weight and pancreatic secretion and growth in response to endogenous and exogenous CCK were examined 7 days after capsaicin treatment. Perivagal application of capsaicin increased plasma CCK levels and significantly increased pancreatic wet weight compared with those in the control rats. Oral administration of CCK-1 receptor antagonist loxiglumide prevented the increase in pancreatic wet weight after capsaicin treatment. In addition, continuous intraduodenal infusion of trypsin prevented the increase in plasma CCK levels and pancreatic wet weight after capsaicin treatment. There were no significant differences in the expression levels of CCK-1 receptor mRNA and protein in the pancreas in capsaicin-treated and control rats. Intraduodenal administration of camostat or intravenous infusion of CCK-8 stimulated pancreatic secretion in control rats but not in capsaicin-treated rats. In contrast, repeated oral administrations of camostat or intraperitoneal injections of CCK-8 significantly increased pancreatic wet weight in both capsaicin-treated and control rats. Present results suggest that perivagal application of capsaicin stimulates pancreatic growth via an increase in endogenous CCK and that exogenous and endogenous CCK stimulate pancreatic growth not via vagal afferent fibers but directly in rats.     

Role of cholecystokinin in mediating GRP-stimulated gastric, biliary and pancreatic functions in man.

To explore the mechanisms of gastrin-releasing peptide (GRP)-induced gut functions in man, we investigated the effect on gallbladder contraction, exocrine pancreatic secretion and gastric acid secretion of a recently developed CCK receptor antagonist, loxiglumide, on GRP-stimulated effects in six healthy human subjects. Intravenous infusion of graded doses of synthetic human GRP (1-27 pmol/kg per h) caused significant and dose-dependent increases in pancreatic enzyme and gastric acid secretions and in gallbladder contraction. Intravenous administration of loxiglumide (10 mg/kg per h) abolished GRP-stimulated gallbladder contraction, augmented gastric acid secretion, but did not affect exocrine pancreatic secretion. The results suggest that endogenously released CCK is (1) responsible for GRP-stimulated gallbladder contraction, and (2) involved in regulating gastric acid secretion. The results further suggest that GRP-stimulated pancreatic secretion is not mediated by CCK, but has a direct response of GRP on the exocrine pancreas.     

A secretin releasing peptide exists in dog pancreatic juice

Canine pancreatic juice has been shown to stimulate exocrine pancreatic secretion in the dog. In the present study we investigated whether there is a secretin-releasing peptide in canine pancreatic juice. Pancreatic juice was collected from the dogs with Thomas gastric and duodenal cannulas while pancreatic secretion was stimulated by intravenous administration of secretin at 0.5 microg/kg/h and CCK-8 at 0.2 microg/kg/h, respectively. The pancreatic juice was separated into three different molecular weight (MW) fractions (Fr) by ultrafiltration (Fr 1; MW > 10,000, Fr 2; MW=10,000-4,000 and Fr 3; MW < 4,000), respectively. All the fractions were bioassayed in anesthetized rats. Fraction 3 dose-dependently and significantly stimulated pancreatic juice flow volume from 78.0% to 99.4% (p<0.05) and bicarbonate output from 128.9% to 202.1% (p<0.01), respectively. Plasma secretin concentration also increased from 1.2 +/- 0.5 pM to 5.0 +/- 0.8 pM and 6.0 +/- 1.0 pM (p<0.05). None of these fractions increased pancreatic protein secretion or plasma CCK level. The stimulatory effect of Fraction 3 on pancreatic secretion and the release of secretin was completely abolished by treatment with trypsin (1 mg/ml for 60 min at 37 degrees C) but not by heating (100 degrees C, 10 min). Intravenous injection of a rabbit anti-secretin serum, which rendered plasma secretin almost undetectable in rat plasma, also abolished Fr 3-stimulated pancreatic secretion of fluid and bicarbonate secretion. These observations suggest that a secretin-releasing peptide exists in the canine pancreatic juice. It is trypsin-sensitive and heat-resistant. This peptide may play a significant physiological role on the release of secretin and regulation of exocrine pancreatic secretion.     

Vasoactive intestinal polypeptide (VIP) in the pig pancreas: role of VIPergic nerves in control of fluid and bicarbonate secretion

Vasoactive intestinal polypeptide (VIP) in the pig pancreas is localized to nerves, many of which travel along the pancreatic ducts. VIP stimulates pancreatic fluid and bicarbonate secretion like secretin. Electrical vagal stimulation in the pig causes an atropine-resistant profuse secretion of bicarbonate-rich pancreatic juice. In an isolated perfused preparation of the pig pancreas with intact vagal nerve supply, electrical vagal stimulation caused an atropine-resistant release of VIP, which accurately parallelled the exocrine secretion of juice and bicarbonate. Perfusion of the pancreas with a potent VIP-antiserum inhibited the effect of vagal stimulation on the exocrine secretion. It is concluded, that VIP is responsible for (at least part of) the neurally controlled fluid and bicarbonate secretion from the pig pancreas.