Regulation Of Pancreatic Exocrine Secretion Research Articles

Cholic acid activation of GPBAR1 does not induce or exacerbate acute pancreatitis but promotes exocrine pancreatic secretion

Obstruction of bile ducts due to gallstones can lead to biliary acute pancreatitis (BAP). According to Perides et al., G protein-coupled bile acid receptor-1 (GPBAR1) mediates BAP. However, Zi’s findings suggest that GPR39, rather than GPBAR1, mediates TLCAS-induced increases in cytosolic calcium and acinar cell necrosis, casting doubt on the role of GPBAR1 in BAP. Numerous G protein-coupled receptors on pancreatic acinar cells utilize Ca2+ and cyclic adenosine monophosphate (cAMP) as second messengers to manage pancreatic exocrine secretion, with significant cross-talk between these signals. The primary bile acid cholic acid (CA) and its conjugated forms are predominant in the human gallbladder. This study aimed to clarify the role and physiological significance of GPBAR1 by investigating the physiological and pathological effects of CA activation on GPBAR1 in pancreatic acinar cells. Isolated rat pancreatic acinar cells were treated with CA and CCK in vitro to observe the effect of CA-induced cAMP signaling on CCK-induced physiological and pathological calcium signaling. In vivo evaluations involved reverse biliopancreatic duct injections of 5% sodium taurocholate (STC) or 5% CA in rats. CA induced intracellular cAMP signaling in a concentration-dependent manner without increasing the intracellular Ca2+ concentration. CA did not independently cause calcium overload or enzyme activation, nor did it exacerbate calcium overload or enzyme activation from high-dose CCK. Reverse biliopancreatic duct injections of 5% CA did not cause acute pancreatitis in the rats. Transcriptomic analysis revealed that 50 μM CA induced changes in gene expression related to protein synthesis in the endoplasmic reticulum and ribosomes. Furthermore, 50 μM CA accelerated the calcium waves and increased the enzyme secretion induced by CCK. GPBAR1 was found on the basolateral membrane in rat pancreatic tissue rather than near the apical region of acinar cells.GPBAR1 activation is not crucial for BAP activity but may play a role in bile acid regulation of pancreatic exocrine secretion, suggesting that GPBAR1 is a potential therapeutic target for pancreatic exocrine insufficiency.

Neurotensin and xenin stimulates pancreatic exocrine secretion through the peripheral cholinergic nerves in conscious sheep

The present study aimed to clarify the effects of neurotensin and xenin on pancreatic exocrine secretion in conscious sheep and their mechanism of actions. The animals were equipped with two silastic cannulae in the common bile duct to separately collect pancreatic fluid and bile, and a silastic cannula in the proximal duodenum to continuously return the mixed fluids. NT and xenin were intravenously injected at range of 0.01–3.0 nmol/kg during the phase I of duodenal migrating motor complex. A single intravenous NT injection significantly and dose-dependently increased pancreatic fluid, protein, and bicarbonate outputs. The effect of NT at 1 nmol/kg was completely inhibited by a background intravenous infusion of atropine methyl nitrate at a dose of 10 nmol/kg/min, however, the effect was not altered by a prior injection of the neurotensin receptor subtype (NTR)-1 antagonist SR 48692 at 60 nmol/kg. Moreover, a single intravenous xenin-25 injection significantly and dose-dependently increased pancreatic fluid and protein output, whereas the effect of xenin-25 did not clearly show dose-dependence. The prior SR 48692 injection at 30 nmol/kg did not significantly alter the effects of xenin-25 at 0.3 nmol/kg, while the atropine infusion significantly inhibited the increase in fluid secretion. Under the atropine infusion, xenin-25 at 0.3 nmol/kg did not increase protein and bicarbonate outputs, whereas the inhibitory effect of the atropine was not significant compared to that of the single injection of xenin-25. A single intravenous injection of NTR-2 agonist levocabastine at 0.1–3 nmol/kg did not alter pancreatic exocrine secretion. These results suggest that both NT and xenin-25 effectively stimulates pancreatic exocrine secretion through the peripheral cholinergic system in sheep and that NTR-2 is not involved in the regulation of pancreatic exocrine secretion, however, we did not precisely determine the role of NTR-1 in the actions of both the peptides on pancreatic exocrine secretion.

Distribution of nociceptin in pancreatic islet cells of normal and diabetic rats.

Nociceptin has been reported to play an important role in the regulation of pancreatic exocrine secretion. Most of the studies performed on nociceptin are mainly physiological rather than morphological in nature. The present study investigated the pattern of distribution of nociceptin in the endocrine pancreas of normal and diabetic rats. Immunohistochemistry, immunofluorescence, Western blot, and double-labeled immunoelectron microscopy were used in this study. Diabetes was induced using streptozotocin (60 mg/kg body weight). Nociceptin-immunoreactive cells were observed in the central and peripheral regions of the islets of both normal and diabetic rat pancreas. The number of nociceptin-positive cells was significantly (P < 0.05) lower in the islet of diabetic rats compared with the control. Immunofluorescence study showed that nociceptin colocalizes with insulin in pancreatic β-cells. The degree of colocalization of nociceptin with insulin was severely deranged after the onset of diabetes. Moreover, immunogold particles conjugated with either nociceptin or insulin were observed on the granules of pancreatic β-cell. The number of nociceptin-labeled colloidal gold particles was significantly lower after the onset of diabetes. Nociceptin is present in pancreatic islets cells and colocalizes with insulin. Nociceptin may have a physiological role in the metabolism of insulin.

Valsartan, a specific angiotensin II receptor blocker, inhibits pancreatic fluid secretion via vagal afferent pathway in conscious rats

Background/aimThe renin–angiotensin system (RAS) exists in the pancreas, but the role of RAS in the regulation of pancreatic exocrine secretion under physiological conditions has been little known. The present study addressed the RAS's effect on the pancreatic secretion by using valsartan, a specific angiotensin II receptor blocker, in conscious rats. MethodMale Wistar rats prepared with pancreatic, biliary, duodenal and jugular vein cannulas were used. To examine the role of RAS in the pancreatic secretion, valsartan at 1, 5, or 25mg/kg was administered into the duodenum via cannula, and volume of pancreatic juice and protein concentration were determined. In addition, to examine the role of RAS in hormone-stimulated pancreatic hypersecretion, pancreatic secretion was examined in response to stimulation of secretin or cholecystokinin after intraduodenal infusion of valsartan at 25mg/kg. Furthermore, to examine the mechanism of action of RAS on pancreatic secretion, intravenous infusion of atropine or perivagal application of capsaicin was conducted and then the pancreatic secretion was examined following intraduodenal infusion of valsartan at 25mg/kg. ResultsVolume of pancreatic juice, but not protein output, significantly decreased after administration of valsartan. However, administration of valsartan did not exert significant effects on secretin- or cholesystokinin-stimulated pancreatic secretion. Treatment with atropine and perivagal application of capsaicin completely abolished the suppressive effect of valsartan on pancreatic juice secretion. ConclusionPresent results suggest that RAS plays a stimulatory role in pancreatic juice secretion via cholinergic afferent pathway without affecting protein secretion and hormonally stimulated pancreatic secretion under physiological conditions.

Regulation of pancreatic exocrine secretion in goats: differential effects of short‐ and long‐term duodenal phenylalanine treatment

Four yearling goats (31.2 ± 2.5 kg), surgically fitted with common bile duct reentrant and duodenal catheter, were used in two 4 × 4 Latin square design experiments to investigate the effects of duodenal infusion of phenylalanine for different times on pancreatic exocrine secretion (PES). In experiment 1 (the long-term experiment), goats were duodenally infused with 0, 2, 4 or 8 g/day phenylalanine for 14 day. Pancreatic juice and jugular blood samples were collected over 1-h intervals for 6 h daily from day 11 to day 14 to encompass a 24-h day. In experiment 2 (the short-term experiment), goats were infused with phenylalanine for 10 h continuously at the same infusion rate as experiment 1 after feed deprivation for 24 h repeated every 10 day. Pancreatic juice and blood samples were collected at 0, 1, 2, 4, 6, 8 and 10 h of infusion. The volume and pH of pancreatic juice were measured, and a 5% subsample was composited and frozen until analysis of enzyme activities. Plasma was frozen until analysis of insulin and cholecystokinin (CCK). In experiment 1, pancreatic juice, α-amylase secretion and plasma CCK concentration responded quadratically (p < 0.05), with the top value observed at the 2 g/day phenylalanine. Trypsin secretion had a quadratic response (p < 0.05), with secretion increasing up to 4 g/day phenylalanine and decreasing thereafter. Phenylalanine linearly decreased pancreatic protein and lipase secretion (p < 0.05). The results of correlation analysis showed significant correlations (p < 0.05) between plasma CCK concentration and secretion of α-amylase and trypsin. However, the short-term phenylalanine infusion did not influence (p > 0.05) pancreatic juice, protein, α-amylase, lipase, trypsin secretion and plasma CCK concentration. These results indicate PES of ruminants is stimulated by phenylalanine and is potentially mediated by CCK in the long-term duodenal infusion treatment, but is not influenced by phenylalanine in the short-term duodenal infusion treatment.

Effects of nitric oxide synthase blockade on dorsal vagal stimulation-induced pancreatic insulin secretion

We and others have previously shown that the dorsal motor nucleus of the vagus (DMV) is involved in regulation of pancreatic exocrine secretion. Many pancreatic preganglionic neurons within the DMV are inhibited by pancreatic secretagogues suggesting that an inhibitory pathway may participate in the control of pancreatic exocrine secretion. Accordingly, the present study examined whether chemical stimulation of the DMV activates the endocrine pancreas and whether an inhibitory pathway is involved in this response. All experiments were conducted in overnight fasted isoflurane/urethane-anesthetized Sprague Dawley rats. Activation of the DMV by bilateral microinjection of bicuculline methiodide (BIM, GABAA receptor antagonist, 100pmol/25nl; 4mM) resulted in a significant and rapid increase in glucose-induced insulin secretion (9.2±0.1ng/ml peak response) compared to control microinjection (4.0±0.6ng/ml). Activation of glucose-induced insulin secretion by chemical stimulation of the DMV was inhibited (2.1±1.1ng/ml and 1.6±0.1ng/ml 5min later) in the presence of the muscarinic receptor antagonist atropine methonitrate (100μg/kg/min, i.v.). On the other hand, the nitric oxide (NO) synthesis inhibitor l-nitroarginine methyl ester (30mg/kg, i.v.) significantly increased the excitatory effect of DMV stimulation on glucose-induced insulin secretion to 15.3±3.0ng/ml and 16.1±3.1ng/ml 5min later. These findings suggest that NO may play an inhibitory role in the central regulation of insulin secretion.

A study of the Effect of Ghrelin on the Regulation of Pancreatic Exocrine Secretion in Male Albino Rats

A study of the Effect of Ghrelin on the Regulation of Pancreatic Exocrine Secretion in Male Albino Rats

Involvement of cannabinoid CB1- and CB2-receptors in the modulation of exocrine pancreatic secretion

The role of the cannabinoid system in the regulation of exocrine pancreatic secretion was investigated by studying the effects of the synthetic CB1- and CB2-receptors agonist, WIN55,212, on amylase secretion in isolated lobules and acini of guinea pig and rat, and the expression of CB-receptors in rat pancreatic tissue by immuno-chemistry and Western-blot analysis in both basal and cerulein (CK)-induced pancreatitis condition. In pancreatic lobules of guinea pig and rat, WIN55,212 significantly inhibited amylase release stimulated by KCl depolarization through inhibition of presynaptic acetylcholine release, but did not modify basal, carbachol- or CK-stimulated amylase secretion. The effect of WIN55,212 was significantly reduced by pre-treatment with selective CB1- and CB2-receptor antagonists. The antagonists, when given alone, did not affect the KCl-evoked response. Conversely, WIN55,212 was unable to affect basal and CK- or carbachol-stimulated amylase release from pancreatic acini of guinea pig and rat. Immunofluorescent staining of rat pancreatic tissues showed that CB1- and CB2-receptors are expressed in lobules and in acinar cells and their presence in acinar cells was also shown by Western-blot analysis. After CK-induced pancreatitis, the expression of CB1-receptors in acinar cells was not changed, whilst a down-regulation of CB2-receptors was observed. In conclusion, the present study shows that WIN55,212 inhibits amylase release from guinea pig and rat pancreatic lobules and, for the first time, that cannabinoid receptors are expressed in lobules of the rat pancreas, suggesting an inhibitory presynaptic role of this receptor system. Finally, in rat pancreatic acinar cells, CB1- and CB2-receptors, expressed both in basal conditions and after CK-induced pancreatitis but inactive on amylase secretion, have an unknown role both in physiological and pathological conditions.

How does cholecystokinin stimulate exocrine pancreatic secretion? From birds, rodents, to humans

The field of cholecystokinin (CCK) stimulation of exocrine pancreatic secretion has experienced major changes in the recent past. This review attempts to summarize the present status of the field. CCK production in the intestinal I cells, the molecular forms of CCK produced and subsequently circulated in the blood, the presence or absence of CCK receptors on the isolated pancreatic acinar cells and the associated signaling for acinar cell secretion, and the actual circuits and sites of action for CCK regulation of exocrine pancreatic secretion in vivo are reviewed in different animal species with an emphasis on birds, rodents, and humans. Clear differences in the relative importance of neural and direct modes of CCK action on pancreatic acinar cells were identified. Rodents seem to be endowed with both modes of action, whereas in humans the neural mode may predominate. In birds, such as duck, the direct mode needs further assistance from pituitary adenylate cyclase-activating peptide/VIP receptors. However, much further work needs to be directed to the neural mode to map out all sites of CCK action and details of the full circuits, and we foresee a major revival for this field of research in the near future.

Effect of jejunal nutrition on pancreatic exocrine secretion in pancreatitis rats and the involvement of the nucleus tractus solitarius

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.

Secretin and the exposition of hormonal control.

Secretin and the exposition of hormonal control.

Neurohormonal control of pancreatic exocrine secretion

The neurohormonal control of pancreatic exocrine secretion is a complex interaction of multiple pathways involving a large number of gut hormones, neurotransmitters, and neuropeptides. Recent studies have elucidated a role for cholecystokinin in the regulation of bicarbonate and fluid secretion from pancreatic duct cells and suggested that cholecystokinin stimulation of human pancreatic acinar cells is likely regulated by an indirect mechanism of stimulation of afferent neurons. Evidence supports the regulation of potassium channels in rat pancreatic acinar cells by the cyclic AMP-mediated agonist secretin. Mechanisms for the regulation of cholecystokinin and secretin release by releasing factors have also been elucidated. The area postrema has been implicated in the mediation of inhibition of pancreatic secretion by the gut hormones peptide YY and pancreatic polypeptide. The neurotransmitter serotonin has been demonstrated to play a role in acid-induced secretin release and in pancreatic secretion stimulated by luminal factors. The regulation of pancreatic exocrine secretion by purines, nitric oxide, and gamma-aminobutyric acid as well as by the neuropeptides pituitary adenylate cyclase-activating peptide, gastrin-releasing peptide, and substance P is reviewed. The role of the central nervous system in modulating pancreatic secretion is also described. This review highlights the recent advances in knowledge of the neurohormonal regulation of pancreatic exocrine secretion.

Modulation of exocrine pancreatic secretion by leptin through CCK 1-receptors and afferent vagal fibres in the rat

In this report, we determined whether leptin could modify the exocrine pancreatic secretion of anaesthetized rats in vivo. Intravenous injection of recombinant murine leptin resulted in a time- and dose-dependent stimulation of exocrine pancreatic secretion, maximally observed with 30 nmol/kg of leptin. This stimulation of pancreatic water, bicarbonate, and protein output was abolished by atropine, hexamethonium, L364,718 ([3 S(−)- N-(1,3-dihydro-1-methyl-2-oxo-5-phenyl-1 H-1,4-benzodiazepine]), a cholecystokinin CCK 1 receptor antagonist or perivagal capsaicin pretreatment, but unaffected by the CCK 2 receptor antagonist L365,260 ([3 R(+)- N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1 H-1,4-benzodiazepin-3yl)- N′-(3-methylphenyl)urea]). In addition, the physiological dose of 3 nmol/kg leptin, ineffective per se, potentiated the secretory effect of 45 pmol/kg of cholecystokinin octapeptide (CCK-8) on exocrine pancreatic secretion. Furthermore, intraperitoneal leptin induced a rapid increase in plasma CCK levels in vivo in the rat. In conclusion, exogenous leptin can modulate exocrine pancreatic secretion through mechanisms involving CCK 1 receptors and capsaicin-sensitive afferent fibres in the rat. Whether this may have a physiological relevance in the postprandial regulation of exocrine pancreatic secretion and thus in nutrient digestion will require further investigations.

Neurohormonal control of exocrine pancreas

The exocrine pancreas is regulated by various hormonal factors derived from the gut through hormone-hormonal and neurohormonal interactions. Physiologic stimuli entering the upper small intestine elicit the release of intestinal hormones and activate sensory reflex mechanisms from the intestinal mucosa to stimulate or inhibit exocrine pancreatic secretion. In addition, the endocrine pancreas, intrapancreatic nerves, and some extrapancreatic neural pathways, with or without mediation by the vagus nerve, are known to participate in regulation of exocrine pancreatic secretion. It has been established that two key intestinal hormones, secretin and cholecystokinin (CCK), in physiologic doses, act through the vagal afferent pathway and interact with each other as well as with other gut hormones. The releases of these two hormones are mediated through the corresponding releasing peptides. In the past few years, the roles of secretin- and CCK-releasing peptides have become more clearly defined. The participation of several neurotransmitters and regulatory peptides in the regulation of exocrine pancreatic secretion has also been established. In addition, neurotransmitters and neuropeptides released from the central nervous system may participate in the regulation of pancreatic secretion. It is conceivable that a few neurotransmitters and neuropeptides are involved in each neural regulatory pathway. However, their roles and sites of action in each pathway remain to be determined.

Roles of 5-HT receptors in the release and action of secretin on pancreatic secretion in rats.

5-Hydroxytryptamine (serotonin, 5-HT) is a hormone and neurotransmitter regulating gastrointestinal functions. 5-HT receptors are widely distributed in gastrointestinal mucosa and the enteric nervous system. Duodenal acidification stimulates not only the release of both 5-HT and secretin but also pancreatic exocrine secretion. We investigated the effect of 5-HT receptor antagonists on the release of secretin and pancreatic secretion of water and bicarbonate induced by duodenal acidification in anesthetized rats. Both the 5-HT(2) receptor antagonist ketanserin and the 5-HT(3) receptor antagonist ondansetron at 1-100 microg/kg dose-dependently inhibited acid-induced increases in plasma secretin concentration and pancreatic exocrine secretion. Neither the 5-HT(1) receptor antagonists pindolol and 5-HTP-DP nor the 5-HT(4) receptor antagonist SDZ-205,557 affected acid-evoked release of secretin or pancreatic secretion. None of the 5-HT receptor antagonists affected basal pancreatic secretion or plasma secretin concentration. Ketanserin or ondansetron at 10 microg/kg or a combination of both suppressed the pancreatic secretion in response to intravenous secretin at 2.5 and 5 pmol x kg(-1) x h(-1) by 55-75%, but not at 10 pmol x kg(-1) x h(-1). Atropine (50 microg/kg) significantly attenuated the inhibitory effect of ketanserin on pancreatic secretion but not on the release of secretin. These observations suggest that 5-HT(2) and 5-HT(3) receptors mediate duodenal acidification-induced release of secretin and pancreatic secretion of fluid and bicarbonate. Also, regulation of pancreatic exocrine secretion through 5-HT(2) receptors may involve a cholinergic pathway in the rat.

Endogenous nitric oxide mediates pancreatic exocrine secretion stimulated by secretin and cholecystokinin in rats.

Nitric oxide (NO) is one of the important biologic mediators in regulation of gastrointestinal (GI) functions, but the influence of NO on the release of secretin and cholecystokinin (CCK) and exocrine pancreatic secretion has not been adequately investigated in the rat. The aim of this study was to determine the role of NO on endogenous and exogenous secretin- or CCK-stimulated pancreatic exocrine secretion both in anesthetized and conscious rats. Experiments were carried out in four different groups of rats with duodenal pancreatobiliary cannulas and jugular vein catheters. Group 1: During duodenal infusion of 0.05N HCl or 15% casein (pH 7.0), N-nitro-L-arginine (NNA), an inhibitor of NO-synthase in graded doses (2.5, 5, 10 mg/kg/h), was infused intravenously. Group 2: One hour after starting intravenous secretin at 5 pmol/kg/h or intravenous CCK-8 at 0.06 microg/kg/h, NNA in graded doses was administered intravenously. Group 3: In conscious rats, NNA (5 mg/kg/h) was given intravenously for 1 hour after a meal. Group 4: L-Arginine at 100 mg/kg/h was infused intravenously during the period of NNA (5 mg/kg/h) infusion in groups 1, 2, and 3. Pancreatic juice was collected at 30-minute intervals to measure volume, as well as output of bicarbonate and protein. At the end of the experiment, plasma secretin, vasoactive intestinal polypeptide (VIP) and CCK levels were determined by radioimmunoassay (RIA). NNA dose dependently inhibited the pancreatic secretion of fluid and bicarbonate stimulated by duodenal acidification, exogenous secretin, and a meal. NNA dose dependently inhibited the pancreatic secretion of protein stimulated by duodenal infusion of casein, exogenous CCK, and a meal. L-Arginine significantly reversed the NNA-induced inhibition of pancreatic secretion in all experiments. NNA did not alter significantly the plasma levels of secretin, VIP, and CCK. Our results indicated that endogenous NO plays a significant role in the regulation of pancreatic exocrine secretion stimulated by secretin and CCK. However, NO does not influence the release of secretin, VIP, or CCK in the rat.

Role of adrenergic receptors in veratridine-stimulated amylase secretion from rabbit pancreatic lobules.

Sympathetic inhibition of pancreatic enzyme secretion has been attributed to vasoconstriction and direct inhibition of acinar cells. We observed both adrenergic inhibition and facilitation of cholinergic transmission in rabbit pancreatic ganglia, which innervate acini. Here we used pancreatic lobules to determine whether adrenergic receptors also regulate synaptic transmission between pancreatic nerves and acini. Stimulation of pancreatic nerve terminals with veratridine (Ver), an activator of voltage-dependent Na+ channels, resulted in a 102% increase in amylase secretion, which was unaffected by alpha and beta receptor antagonists but inhibited 65% by atropine. At a concentration of 10 microM, norepinephrine inhibited (38%) and epinephrine potentiated (40%) Ver-stimulated secretion. At the same concentration, the alpha2 agonist clonidine (Clon) inhibited (39%), whereas the nonselective beta agonist isoproterenol (Iso) and the selective beta3 agonist BRL 37344 potentiated (71 and 67%, respectively) nerve-stimulated secretion. The effects of Clon and Iso and BRL 37344 were antagonized by yohimbine and propranolol, respectively. Phenylephrine, dobutamine, and terbutaline had no effect. Neither basal, bethanechol-stimulated, nor noncholinergic nerve-stimulated secretion was significantly altered by Clon or Iso. Thus, cholinergic nerve terminals innervating pancreatic acini exhibit both inhibitory alpha2 and atypical facilitatory beta adrenergic receptors. The apparent lack of adrenergic innervation suggests that adrenergic receptors on the nerve terminals of cholinergic pancreatic neurons are under hormonal control by circulating catecholamines. These results provide further evidence that intrinsic pancreatic neurons, which supply most, if not all, of the cholinergic innervation of acini, are important sites of sympathetic regulation of pancreatic exocrine secretion.

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 μ/gk/gh and CCK-8 at 0.2 μg/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 ° C) but not by heating (100 ° 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.

Neurohumoral control of the exocrine pancreas

Recent advances in the study of pancreatic exocrine secretion are reviewed, with an emphasis on neurohumoral mechanisms. In the past year, cDNA for the human pancreatic sodium-bicarbonate cotransporter was cloned, and the expressed protein was localized to pancreatic acini and ductal cells. Recent information suggests that the cholecystokinin B receptor has a role in pancreatic amylase release. Further evidence supports the concept of a protease-sensitive negative feedback mechanism regulating pancreatic exocrine secretion. Study of the expression of the receptors responsible for the regulation of pancreatic function has proven fruitful in the determination of the molecular mechanisms of hormone signal transduction and desensitization. Studies of peptide 1, pituitary adenylate cyclase-activating peptide, and gastrin-releasing peptide have shown how these peptides participate in the regulation of pancreatic secretion and have provided information on intracellular signaling pathways obtained using rat pancreatic tumor cells. Neural regulation via cholinergic receptors in isolated pancreatic acini and the mechanisms responsible for other neurotransmitters, such as calcitonin gene-related peptide, histamine, and dopamine, are reviewed. This review highlights recent discoveries in the neurohumoral regulation of pancreatic exocrine secretion.

Pancreatic hypersecretion in the jejunal-bypass rat.

We diverted bile and pancreatic juice from jejunal blind loops of different lengths in conscious rats to see if the pancreatic secretory response was dependent on the length of the jejunal blind loop. Short-term bile and pancreatic juice diversion from a short jejunal blind loop, representing only 8-10% of the total length of the small intestine, stimulated a significant increase in pancreatic exocrine secretion. Short-term bile and pancreatic juice diversion from jejunal blind loops of increasing length resulted in a progressive decrease in the pancreatic secretory response to diversion (i.e., there appears to be a length-dependent inhibition of the pancreatic secretory response to short-term bile and pancreatic juice diversion from the jejunum). Cholinergic receptor blockade with atropine eliminated this length-dependent inhibition of pancreatic exocrine secretion during short-term bile and pancreatic juice diversion. In contrast to what was observed with short-term bile and pancreatic juice diversion, there was a length-dependent increase in pancreatic secretion during long-term bile and pancreatic juice diversion. The jejunal-bypass rat model can facilitate the investigation of the intestinal mechanisms mediating feedback regulation of pancreatic exocrine secretion.