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Four goats (30.1 ± 1.3 kg) with common bile duct re-entrant catheter and duodenal catheter were used to evaluate the effects of duodenal leucine infusion on pancreatic exocrine secretion and plasma parameters with two 4 × 4 Latin square design experiments. In the long-term infusion experiment, goats were fed twice daily [700 g/day, dry matter ( DM) basis] at 8:00 and 18:00 hours and were duodenally infused with 0, 3, 6, 9 g/day leucine for 14 days. Pancreatic juice and jugular blood samples were collected over 1-h intervals for 6 h daily from d 11 to 14 days to encompass a 24-h day. In the short-term experiment, goats were infused leucine for 10 h continuously at the same infusion rate with Experiment 1 after feed deprivation for 24 h repeated every 10 days. Pancreatic juice and blood samples were collected at 0, 1, 2, 4, 6, 8 and 10 h of infusion. The results showed that the long-term leucine infusion did not affect pancreatic juice secretion, protein output, trypsin and lipase secretion and plasma insulin concentration, but linearly increased α-amylase secretion. No changes in pancreatic protein and lipase secretion were observed in the short-term infusion. Pancreatic juice and α-amylase secretion responded quadratically, with the greatest values observed in the 3 and 6 g/day leucine respectively. Trypsin secretion linearly decreased, while plasma insulin concentration increased linearly with increased leucine infusion. The results demonstrated that duodenal leucine infusion dose and time dependently regulated pancreatic enzyme secretion not associated with the change in plasma insulin concentration. [ABSTRACT FROM AUTHOR]

Abstract: Background: The relationship between prognosis of advanced pancreatic cancer and exocrine secretion impairment is unknown. Aim: To investigate a possible correlation between faecal elastase-1 value and survival in advanced pancreatic cancer. Methods: 194 patients with advanced pancreatic cancer were prospectively enrolled between 2007 and 2009 and underwent faecal elastase-1 measurement. Exocrine pancreatic secretion was defined as “moderately reduced” (faecal elastase-1: 100–200μg/g), “severely reduced” (faecal elastase-1<100 and >20μg/g) and “extremely reduced” (faecal elastase-1≤20μg/g). Results: Median faecal elastase-1 was 204μg/g (interquartile range 19; 489). Overall, 48 patients (25%) had an extremely reduced exocrine pancreatic secretion, 28 (14%) a severely reduced exocrine pancreatic secretion and 21 (11%) a moderately reduced exocrine pancreatic secretion. Patients with extremely reduced exocrine pancreatic secretion had higher rates of pancreatic head localizations (P <0.01) and of jaundice (P <0.01). Median overall survival was 10.5months. Patients with faecal elastase-1≤20μg/g had a worse prognosis (median survival: 7 versus 11months, P =0.031). Presence of metastases (Hazard ratio 1.81, P <0.0001), haemoglobin≤12g/L (Hazard ratio 2.12, P =0.001), albumin≤40g/L (Hazard ratio 1.64, P =0.010) and FE-1≤20μg/g (Hazard ratio 1.59 P =0.023) resulted as independent predictors of survival in advanced pancreatic cancer patients. Conclusions: A low value of faecal elastase-1 is strongly correlated with a poor survival in advanced pancreatic cancer. [Copyright &y& Elsevier]

Galanin inhibits pancreatic amylase secretion from mouse lobules induced by physiological concentrations of caerulein via an insulin- dependent mechanism. We aimed to determine the effect and elucidate the mechanism of action of exogenous galanin on pancreatic amylase secretion induced by supramaximal concentrations of caerulein. Amylase secretion from isolated murine pancreatic lobules was measured. Lobules were coincubated with galanin (10-1210-7 M) and caerulein (10-7M). Lobules were preincubated with atropine (10-5 M), tetrodotoxin (10-5 M), diazoxide (10-7 M), or the galanin antagonist galantide (10-12̱10-7 M) for 30 mm followed by incubation with caerulein alone, or combined with galanin (10-12 M). Lobules were also coincubated with combinations of galanin (10- 12 M), caerulein, octreotide (10-1210-7 M) or cyclo-(7-aminohep- tanoyl-Phe-D-Trp-Lys-Thr[BZL]), a somatostatin receptor antagonist (10-9 M). Amylase secretion was expressed as percent of total lobular amylase. Caerulein stimulated amylase secretion to 124% of control. Diazoxide pretreatment abolished the caerulein-stimulated amylase secretion, whereas atropine or tetrodotoxin caused a partial inhibition. Galanin (10-12̱10-7 M) potentiated caerulein-stimulated amylase secretion to 160% of control. Preincubation with a combination of atropine and diazoxide abolished the potentiating effect of galanin, indicating muscarinic receptor and insulin mediation. Preincubation with galantide abolished the galanin effect, implying galanin receptor involvement. Coincubation with caerulein, galanin, and octreotide significantly reduced the potentiating effect galanin. However, coincubation with the somatostatin receptor antagonist, alone or in combination with galanin, significantly increased caerulein-stimulated amylase secretion to a level comparable to the galanin potentiation. Taken together, these data suggest that, at supramaximal caerulein concentrations, galanin acts via its receptors to further increase caerulein-stimulated amylase secretion by inhibiting the caerulein-induced release of somatostatin. [ABSTRACT FROM AUTHOR]

Pancreatic exocrine secretion is affected by galanin, but the mechanisms involved are unclear. We aimed to determine the effect and elucidate the mechanism of action of exogenous galanin on basal and stimulated pancreatic amylase secretion in vitro. The effect of galanin on basal-, carbachol-, and caerulein-stimulated amylase secretion from isolated murine pancreatic lobules was measured. Carbachol and caerulein concentration-response relationships were established. Lobules were coincubated with galanin (10-12 M to 10-6 M), carbachol (10-6 M), or caerulein (10-10 M). Lobules were preincubated with atropine (10-5 M), tetrodotoxin (10-5 M), hexamethonium (10-5 M), or diazoxide (10-7 M and 10-4 M) for 30 mm followed by incubation with caerulein (10-10 M) alone or combined with galanin (10-12 M). Amylase secretion was expressed as percent of total lobular amylase. Immunohistochemical studies used the antigen retrieval technique and antisera for galanin receptor (GALR) 1, 2, and 3. Carbachol and caerulein stimulated amylase secretion in a concentration-dependent manner with maximal responses of two- and 1.7-fold over control evoked at 10-6 M and 10-10 M, respectively. Galanin (10-12 M) completely inhibited caerulein-stimulated amylase secretion but had no effect on carbachol-stimulated or basal secretion. Atropine and tetrodotoxin pretreatment abolished the caerulein-stimulated amylase secretion, whereas hexamethonium had no significant effect. Diazoxide significantly reduced caerulein-stimulated amylase secretion by ∼80%. Galanin did not affect caerulein-stimulated amylase secretion in the presence of hexamethonium or diazoxide. Glucose-stimulated amylase secretion was also inhibited by galanin. Immunohistochemistry revealed islet cells labeled for GALR2. These data suggest that galanin may modulate caerulein-stimulated amylase secretion by acting on cholinergic nerves and/or islet cells possibly via GALR2 to regulate insulin release. [ABSTRACT FROM AUTHOR]

Abstract: We previously reported that C-type natriuretic peptide (CNP) increases amylase release in isolated pancreatic acini through natriuretic peptide receptor C activation and enhances pancreatic exocrine secretion via vagal pathways when applied to the brain. In the present study we sought to establish whether CNP was involved in the peripheral regulation of pancreatic secretion. Anesthetized rats were prepared with pancreatic duct cannulation, pyloric ligation and bile diversion into the duodenum. CNP dose-dependently enhanced pancreatic flow, chloride and protein excretion but did not modify bicarbonate output. A selective natriuretic peptide receptor C agonist enhanced pancreatic flow and mimicked CNP-evoked protein output but failed to modify chloride secretion. Truncal vagotomy, perivagal application of capsaicin and hexamethonium reduced CNP-evoked pancreatic flow and abolished chloride excretion but did not affect protein output. Furthermore, pre-treatment with atropine reduced both CNP-stimulated pancreatic flow and chloride excretion but failed to modify protein excretion. Partial muscarinic blockade of CNP-evoked chloride output suggested that mediators other than acetylcholine were involved. However, CNP response was unaltered by cholecystokinin and vasoactive intestinal peptide receptor blockade or by nitric oxide synthase inhibition. In conclusion, CNP-stimulated pancreatic flow through the activation of the natriuretic peptide receptor C and the vago-vagal reflex but it increased protein output only by natriuretic peptide receptor C activation and chloride excretion by vago-vagal reflexes. Present results suggest that CNP may play a role as a local regulator of the exocrine pancreas. [Copyright &y& Elsevier]

Previous studies have suggested that somatostatin inhibits pancreatic secretion at a central vagal site, and the dorsal vagal complex (DVC) is involved in central feedback inhibition of the exocrine pancreas. The aim of this study was to investigate the effect of exogenous somatostatin in the DVC on pancreatic secretion and the somatostatin receptor subtype(s) responsible for the effect. The effects of somatostatin microinjected into the DVC on pancreatic secretion stimulated by cholecystokinin octapeptide (CCK-8) or 2-deoxy-D-glucose (2-DG) were examined in anesthetized rats. To investigate the somatostatin inhibitory action site, a somatostatin receptor antagonist [SRA; cyclo(7-aminoheptanoyl-Phe-D-Trp-Lys-Thr)] was microinjected into the DVC before intravenous infusion of somatostatin and CCK-8/2-DG. The effects of injection of a somatostatin receptor-2 agonist (seglitide) and combined injection of somatostatin and a somatostatin receptor-2 antagonist (CYN 154806) in the DVC on the pancreatic secretion were also investigated. Somatostatin injected into the DVC significantly inhibited pancreatic secretion evoked by CCK-8 or 2-DG in a dose-dependent manner. SRA injected into the DVC completely reversed the inhibitory effect of intravenous administration of somatostatin. Seglitide injected into the DVC also inhibited CCK-8/2-DG-induced pancreatic protein secretion. However, combined injection of somatostatin and CYN 154806 did not affect the CCK-8/2-DG-induced pancreatic secretion. Somatostatin in the DVC inhibits pancreatic secretion via somatostatin receptor-2, and the DVC is the action site of somatostatin for its inhibitory effect. [ABSTRACT FROM AUTHOR]

Ghrelin receptors are present in the central nervous system. We hypothesized that ghrelin released from the stomach acts as an endocrine substance and stimulates brain stem vagovagal circuitry to evoke pancreatic secretion. In an in vivo anesthetized rat model, an intravenous infusion of ghrelin at doses of 5, 10, and 25 nmol increased pancreatic protein secretion from a basal level of 125 ± 6 to 186 ± 8, 295 ± 12, and 356 ± 11 mg/h, respectively. Pretreatment with atropine or hexamethonium or an acute vagotomy, but not a perivagal application of capsaicin, completely abolished pancreatic protein secretion responses to ghrelin. In conscious rats, an intravenous infusion of ghrelin at a dose of 10 nmol resulted in a 2.2-fold increase in pancreatic protein secretion over basal volume. Selective ablation of the area postrema abolished pancreatic protein secretion stimulated by intravenous infusion of ghrelin but did not alter the increase in pancreatic protein secretion evoked by diversion of bile-pancreatic juice. Immunohistochemical staining showed a marked increase in the number of c-Fos-expressing neurons in the area postrema, nucleus of the solitary tract, and dorsal motor nucleus of the vagus after an intravenous infusion of ghrelin in sham-lesioned rats; selective ablation of the area postrema eliminated this increase. In conclusion, ghrelin stimulates pancreatic secretion via a vagal cholinergic efferent pathway. Circulating ghrelin gains access to the brain stem vagovagal circuitry via the area postrema, which represents the primary target on which peripheral ghrelin may act as an endocrine substance to stimulate pancreatic secretion. [ABSTRACT FROM AUTHOR]

Abstract: The observation that in dogs electrical stimulation of the vagus nerve elicited a strong secretory activity of the pancreas, prompted I. P. Pavlov in 1888 to conclude that the pancreatic secretory response to nutrients is mediated by enteropancreatic reflexes involving the vagus nerves. It took, however, more than 90 years until by studying the latency of pancreatic amylase response to exogenous and endogenous stimuli for the first time experimental evidence was provided for the actual existence of cholinergic vago-vagal enteropancreatic reflexes. Follow-up studies, based on stepwise extrinsic denervation of the pancreas, ruled out possible splanchnic pathways for enteropancreatic reflexes. In more recent years, experiments utilizing specific antagonists demonstrated a physiological role for both cholinergic M1 and cholecystokinin (CCK) receptors within the enteropancreatic reflex. At least a significant portion of the cholinergic fibres of the enteropancreatic reflex end on muscarinic receptors of the subtype M1. CCK, the most important hormone stimulating pancreatic enzyme secretion, appears to act at least in part on CCK receptors located on vagal afferent nerves, which in turn elicit a vago-vagal reflex, implying that CCK exerts its effect on the pancreas at least in part through vago-vagal reflexes. Furthermore, pharmacological blockade of CCK receptors totally abolished the early pancreatic amylase response to intestinal nutrients, suggesting that the activation of (probably vagal) CCK receptors is essential to run the enteropancreatic reflex. [Copyright &y& Elsevier]

Abstract: Jejunal nutrition is currently used as a fundamental therapeutic measure for acute pancreatitis. Its impact on pancreatic exocrine secretion (PES) is still on dispute. The aim of this study was to determine the effect of jejunal nutrition on PES and illuminate whether NTS is involved in the regulation of PES. Firstly, we established experimental acute cutaneous pancreatitis (ACP) and acute necrotic pancreatitis (ANP) rat models, and measured the volume and protein levels of pancreatic fluid in normal and pancreatitis rats, and found that pancreatitis rats had a significantly lower pancreatic fluid volume and protein level than the normal rats. Then, we gave 0.3 mol/l maltose and 3% saline as jejunal nutrition were given to the two groups, respectively, and found that the jejunal nutrition did not increase the PES levels in both groups. In addition, we analyzed c-Fos expression in the nucleus tractus solitarius (NTS), and found c-Fos expression in NTS was stronger in rats who were given the jejunal nutrition than in those who were not. These findings suggest that jejunal nutrition excites vagal afferent nerve fibers at pancreatitis rats, and the excitation can be transmitted to medulla oblongata, but do not induce changes in PES. It is likely that the central integration mechanism, pathway of vagal efferent nerve or status of effector in acute pancratitis may be different from normal physiological conditions. [Copyright &y& Elsevier]

Pancreatic exocrine secretion is known to be facilitated by gastric antral distension via long- and short-route reflexes. In this study, we studied the effects of gastric distension on intra-pancreatic nerve discharges and blood insulin level as well as pancreatic exocrine secretion. Mongrel dogs were anesthetized with ketamine and thiopental, and immediately decerebrated. This study consisted of two series of experiments. In the first series, efferent discharges in an intra-pancreatic nerve branch were recorded, and its responses to antral distension were analyzed. In the second series, effects of antral distension on pancreatic exocrine secretion and blood insulin level were observed before and after vagotomy in splanchnicectomized dogs. Efferent discharges in a pancreatic nerve branch were increased by antral distension. Neither vagotomy nor splanchnicectomy produced obvious changes in the neural response. In splanchnicectomized dogs, antral distension elevated blood insulin level and increased pancreatic exocrine secretion. After subsequent vagotomy, these effects were reduced, but the increases were still greater than 50%. These results indicate that the antro-pancreatic short-route reflex plays a significant role in exocrine secretion, and also suggest that insulin release is increased by antral distension independent of blood glucose level. [Copyright &y& Elsevier]

The present report gives an overview of the experimental, pharmacological and molecular investigations that have been undertaken during the past two decades to characterize and identify the muscarinic receptor subtype(s) involved in the cholinergic control of pancreatic exocrine secretion in humans and different animal species. The results published in the literature clearly indicate that both M1 and M3 receptors contribute to the regulation of pancreatic enzyme secretion, although contradictory conclusions have been drawn from secretory studies using specific M1 and M3 receptor antagonists in vivo and in vitro. Binding studies using specific M1 and M3 receptor antagonists have supported the existence of both M1 and M3 receptors on pancreatic acinar cells, which was confirmed by the demonstration of specific mRNA for both receptor subtypes in rat pancreatic acinar cells. In addition, experimental evidence exists that nonacinar (possibly presynaptic) M1 receptors also contribute to the control of pancreatic enzyme secretion. The role of the different muscarinic receptor subtypes in the control of pancreatic fluid and bicarbonate output, however, still needs to be clarified. Future research should cover the evaluation of the relative contribution of the different receptor subtypes to the regulation of pancreatic exocrine function, the localization of the receptors involved as well as possible species differences. [ABSTRACT FROM AUTHOR]

Previously we demonstrated that circulating peptide YY (PYY), which inhibits pancreatic exocrine secretion, binds to specific receptors in the area postrema (AP); therefore we have tested the hypothesis that the removal of the AP (APX) will alter the effects of PYY on pancreatic secretion in awake rats. One-month after AP lesion or sham lesion, rats were implanted with pancreatic, biliary, duodenal, and intravenous catheters. After recovery from the surgery, unanesthetized rats were infused with vehicle or PYY (30 pmol/kg/hr or 100 pmol/kg/hr) under basal or 2-deoxy-D-glucose (2-DG) stimulated (75 mg/kg, intravenous bolus) conditions. PYY at 30 pmol/kg/hr inhibited basal pancreatic fluid secretion in sham-operated rats, but not APX rats. PYY at 100 pmol/kg/hr stimulated basal pancreatic protein secretion in sham-operated rats, and this effect was also lost in APX rats. PYY at 30 and 100 pmol/kg/hr inhibited peak 2-DG stimulated protein secretion to a greater extent in APX rats as compared to sham-operated rats (P < 0.05). Since PYY inhibition of basal pancreatic secretion is AP dependent and inhibition of 2-DG stimulated pancreatic secretion is AP independent, we conclude that the 2-DG pathway of pancreatic secretion differs from the pathway responsible for basal secretion, and that APX potentiates the inhibitory effect of PYY on the 2-DG pathway. [ABSTRACT FROM AUTHOR]

Background: Intraileal carbohydrates and lipids affect the pancreatic exocrine secretion, but the effect of intraileal amino acids and the role of the extrinsic nerves of the ileum as mediators of the pancreatic bicarbonate and enzyme output are unknown. Methods: Four dogs underwent total extrinsic denervation of the entire ileum. Thomas-like cannulas were placed into the stomach, duodenum (to collect pure pancreatic juice), and at the jejuno-ileal junction. Eight neurally intact control dogs received only the three fistulas. After recovery, in both sets of dogs, dose-response studies of the pancreatic secretory response to intraileal infusion with graded loads of tryptophan (0.12–10.0 mmol/h) were performed, given against an intravenous (iv) background of secretin (20.5 pmol/kg/h) and cerulein (29.6 pmol/kg/h). On separate days, control experiments with intraileal infusion of 0.15 M NaCl were performed. Results: In both sets of dogs, iv secretin plus cerulein significantly ( p<0.05) increased pancreatic bicarbonate and protein output above basal. Intraileal tryptophan caused a dose-dependent decrease in the pancreatic bicarbonate and protein response to secretin plus cerulein. In the dogs with denervated ileum, this inhibition was significantly stronger than in the intact animals. In both sets of dogs, the 225-min integrated bicarbonate (IBR) and protein response (IPR) to all loads of tryptophan were significantly lower than in control experiments. Both IBR and IPR were significantly lower in the denervated as compared with the intact animals. Conclusions: 1) Extrinsic denervation of the entire ileum is a valuable preparation to study the role of nerves in the control of pancreatic exocrine secretion; 2) both in the intact and denervated animals the amino acid tryptophan induces an “ileal brake” of the hormonally stimulated pancreatic bicarbonate and protein output; 3) the extrinsic nerves of the ileum are probably not the dominant mediators of the inhibitory action of intraileal tryptophan but rather counteract this effect. [ABSTRACT FROM AUTHOR]

The effects of tetraprenylacetone (TPN), an acyclic polyisoprenoid with antiulcer actions, on pancreatic exocrine secretion, and its preventive and therapeutic effects on acute pancreatitis in two experimental models were studied in rats. Intraduodenal administration of TPN (0, 100, 200 and 400 mg/kg/h) caused dose-dependent increases in pancreatic juice and bicarbonate output without increasing protein output and plasma cholecystokinin (CCK) concentrations. TPN-stimulated pancreatic exocrine secretion was completely abolished by antisecretin serum but it was not by CCK receptor antagonist loxiglumide (50 mg/kg/h). In acute pancreatitis induced by four subcutaneous injections of 20 μg/kg cerulein at hourly intervals over, 3 h, TPN (400 mg/kg) given by an oral route either 1 h before the first cerulein injection or immediately after the last injection significantly reduced the increases in serum amylase and lipase activities and pancreatic wet wt. Pretreatment with TPN caused histologic improvements, whereas posttreatment failed to ameliorate histologic alterations. In severe type of acute pancreatitis induced by retrograde intraductal injection of 1.0 mL/kg of 4% sodium taurocholate, TPN exerted no apparent beneficial effects on biochemical and histologic alterations of acute pancreatitis. It is concluded that TPN given by an oral route stimulates pancreatic exocrine secretion through an increase in endogenous secretin release and causes beneficial effects on the experimental model of mild acute pancreatitis in rats. [ABSTRACT FROM AUTHOR]

The exocrine pancreas secretes throughout 24 hours. In both interdigestive and postprandial states, pancreatic secretion is regulated by neural and hormonal actions, and neurohormonal interactions. At the turn of this century, the prevailing theory of Pavlov (1) that pancreatic exocrine secretion was exclusively regulated by secretory fibers in both vagi and splanchnic nerves was refuted by Bayliss and Starling in 1902, who put forward their hypothesis that pancreatic secretion was stimulated by a circulating hormone, 'secretin,' which was released by hydrochloric acid from the duodenal mucosa (2). Soon, Pavlov conceded to the hypothesis of Bayliss and Starling. Pavlov adopted the theory of a dual mechanism-nervous and hormonal-of the regulation of pancreatic secretion. In recent decades, explosions of new information about old and newly discovered gut hormones or peptides and neuropeptides have resulted in a better understanding of the regulatory mechanism of the exocrine pancreas, and also opened new, exciting frontiers in the investigations of the physiology and patho-physiology of pancreatic secretion. [ABSTRACT FROM AUTHOR]

Secretin stimulates pancreatic water and CO excretion as well as pancreatic blood flow. It has been questioned whether the production (i.e. water and CO excretion) is reflected in the input-output difference of nutrients. In pentobarbital anesthetised dogs, pancreatic exocrine secretion was stimulated by secretin, (Karolinska), 1 U/kg injected as an i.v. bolus. Secretion was maximally increased at 2 min after the secretin shot and returned to a basal value at between 16 and 32 min after secretin. Blood flow was also maximally increased at 2 min, but decreased to the basal value at between 8 and 16 min. O extraction first decreased (at 2 min) and then gradually increased until it was higher than the basal value (at 16 min) and then returned to the basal level (at 32 min). O consumption increased quickly, reached a plateau, lasting from 1 to 16 min, and then decreased to the basal level (32 min). CO transfer from blood to tissue reached a maximum at 4 min and then decreased to the basal value (at between 16 and 32 min). The curves for CO transfer from tissue to pancreatic secretion and for CO in the secretion had the same shape. It is concluded that the curve of production (of water and CO excretion) parallels the curve of O consumption fairly well. The O consumption curve did not correlate either with the blood flow curve or with the O extraction curve. About one quarter of the excreted CO originated from pancreatic metabolism and the remaining three quarters were transferred from blood, through the pancreatic tissue into the secretion. The increase in O consumption was achieved by an increase in blood flow, followed by an increase in O extraction. The release of a vasodilator metabolite by the pancreatic cells upon arrival of the secretin molecules, may explain both the increase in blood flow and the successive increase in O extraction. Therefore these data can be interpreted according to the model for metabolic control of tissue oxygenation. [ABSTRACT FROM AUTHOR]

Vasopressin decreases blood flow as well as secretory flow in the pancreas. The question raised was whether the blood flow decrease is the determinant of the decrease in secretion or quite the reverse. In pentobarbital anesthetized dogs, secretory flow was first increased to a steady level by infusion of secretin. At this steady state, O consumption and O extraction were increased, while blood flow remained at the control level, indicating an increase in the area available for exchange i.e. an increase in capillary density. At increasing doses of vasopressin, secretory flow decreased, arterial flow decreased, and O extraction increased, while O consumption decreased and venous-arterial CO concentration difference was not changed. At the same time CO transport decreased, CO concentration in the secretion was unchanged and CO output in the secretion was decreased. The decrease in blood flow was always seen about 25 s before the decrease in secretory flow, strongly suggesting that the decrease in blood flow induced the decrease in secretory flow. A higher dose of vasopressin was required to decrease the O consumption (i.e. this effect was less sensitive) than to increase O extraction. The decrease in secretory flow and the decrease in blood flow showed an intermediate sensitivity. So O consumption seems to be preserved at a high level by the increase in O extraction. It is concluded that the vasopressin-induced decrease in blood flow is the determinant of the decrease in secretory flow. This phenomenon is discussed in terms of the model for metabolic control of tissue oxygenation. [ABSTRACT FROM AUTHOR]

We investigated the effects of porcine pancreastatin on the endocrine and unstimulated exocrine secretion of isolated, perfused porcine pancreas. Pancreastatin in a concentration of 10mol/l had no effect on basal secretion of insulin, glucagon and somatostatin at a perfusate glucose concentration of 5 mmol/l ( n=4) and neither at 10 nor 10 mol/l influenced the hormone responses to acute elevations of perfusate glucose concentration from 3.5 to 11 mmol/l ( n=7). This elevation strongly stimulated insulin secretion and inhibited glucagon secretion. Exocrine secretion was not affected by pancreastatin. The results suggest that pancreastatin does not directly influence pancreatic secretion. [ABSTRACT FROM AUTHOR]

Various cannulae have been devised to serve in experiments for collecting pancreatic juice. In this study we created a pancreatic fistula in dogs through a modification of Herrera's method. Since it is advisable to make as small a duodenal pouch as possible to collect almost all the secreted pancreatic juice, both ends of the pouch were closed by an inverted continuous all-layer suture. The lateral flange of the cannula was then introduced into the pouch to sample the pancreatic juice. Duodenoduodenostomy was performed to restore continuity of the alimentary tract, and the other end was inserted into the duodenum 3 cm distal to the anastomosis on the anal side. The exocrine pancreatic secretion of these dogs responded well to food ingestion, with a peak level of 14.5±5.4 ml/15 min appearing after 30 to 45 min in a postprandial state. Moreover, the animals were able to survive and be utilized for experiments for a period of 3 to 5 months. This experimental model is therefore considered to be of great value for the investigation of exocrine pancreatic secretion. [ABSTRACT FROM AUTHOR]

We assessed the duration of the anti-cholecystokinin (CCK) action of FK480, a new non-peptide CCK-A receptor antagonist developed in Japan, in an in vivo study in rats, comparing it with CR 1505. Pancreatic exocrine secretion stimulated by intravenous infusion of CCK-8 (0.06 μg/kg per h) was measured at intervals of 0-24 h after the oral administration of FK480 (1.5 mg/kg) and CR 1505 (30 mg/kg). FK480 significantly inhibited both CCK-stimulated pancreatic juice volume flow and amylase output 0, 4, 8, and 12h after oral administration, whereas the inhibitory effect of CR 1505 had completely disappeared by 8h after oral administration. It was concluded that orally administered FK480 has a prolonged anti-CCK action. [ABSTRACT FROM AUTHOR]

We investigated the possible role of endogenous secretin and cholecytokinin (CCK) on oleic acid-stimulated pancreatic exocrine secretion in anesthetized rats. Intraduodenal infusion of oleic acid (pH 6.5) in three different doses (0.06, 0.25 and 1 mmole/hr) resulted in dose-related increases in pancreatic juice volume, bicarbonate and amylase outputs (r=0.665, 0.736 and 0.517, respectively) (P<0.001). Plasma secretin and CCK concentrations also elevated significantly in response to oleic acid, in a dose-related manner (r=0.721 and 0.546, respectively) (P<0.001). There were statistically significant correlations between plasma secretin concentrations and bicarbonate outputs, and between plasma CCK concentrations and amylase outputs in response to oleic acid (P<0.01). Potent CCK antagonist, CR 1409 (5 mg/kg.hr) administered intravenously suppressed completely increase in amylase output induced by oleic acid, and partially in juice volume and bicarbonate output. It is concluded that both endogenous secretin and CCK play important roles on oleic acid-induced pancreatic secretion in rats. [ABSTRACT FROM AUTHOR]

Exocrine pancreatic secretion to intravenous injections of a new stimulant of gastrointestinal motility, R51 619 (cisapride) was studied in conscious rats, and in the isolated pancreatic acini in vitro. The injection of cisapride (2 mg/kg) significantly increased fluid, bicarbonate and protein output in vivo. Atropine completely abolished the pancreatic responses to cisapride, and CR 1409, a new glutaramic acid derivative and a competitive cholecystokinin (CCK) inhibitor, tended to decrease the cisapride-induced pancreatic exocrine secretion. However, amylase release and Ca efflux from the isolated pancreatic acini were not stimulated. These results suggest that cisapride indirectly affects the pancreatic exocrine secretion primarily by releasing acethycholine from the intrapancreatic nerve endings and in part by releasing CCK from the duodenum, but has no direct action on the pancreas. [ABSTRACT FROM AUTHOR]

We examined diurnal changes of pancreatic exocrine secretion and plasma levels of cholecystokinin (CCK) and human pancreatic polypeptide (hPP) in men with postoperative transient external pancreatic drainage (3 with pancreatico-jejunostomy: PJ, and 5 with pancreato-duodenectomy: PD). Plasma CCK levels increased and the pancreatic exocrine secretion showed a corresponding increase after meals in both groups. In the PJ group hPP levels increased after meals and there was a significant correlation between the plasma levels of CCK and hPP. In the PD group the plasma hPP levels were not detectable throughout the study and there was a better correlation between the exocrine secretion and the plasma CCK levels than in the PJ group. Plasma CCK levels showed rhythmic changes associated with pancreatic exocrine secretion, with no significant changes in plasma glucose and insulin in the night (24:00-07:00). These results suggested that (1) the resection of the pancreatic head which is rich in hPP contents led to a complete loss of anti-CCK effects on CCK, and that (2) fluctuation in plasma CCK levels, in the fasting state, might initiate pancreatic exocrine secretion. [ABSTRACT FROM AUTHOR]