Inhibitory effects of pirenzepine on cholecystokinin and secretin stimulation on exocrine and endocrine rat pancreas

Effects of pirenzepine, a newly developed anticholinergic drug, on exocrine and endocrine pancreatic functions stimulated by cholecystokinin octapeptide and secretin were studied in both isolated pancreatic acini and the isolated perfused pancreas of rats. In the isolated acini, pirenzepine did not have any significant effect on cholecystokinin-inducec amylase release but caused an inhibition of amylase secretion initiated by secretin and shifted the dose-response curve for amylase secretion to the right. In the isolated perfused pancreas stimulated with 100 pM cholecystokinin octapeptide, addition of 10 M pirenzepine before as well as after 20 min of perfusion significantly inhibited pancreatic juice flow but not enzyme output. In contrast, pirenzepine caused an inhibition of secretin-stimulated enzyme secretion, but not pancreatic juice flow. The stimulatory effect of both cholecystokinin octapeptide and secretin on insulin secretion was also inhibited by pirenzepine. The present data indicate that pirenzepine may have an influence on pancreatic exocrine and endocrine function by inhibiting endogenous cholinergic activity of the pancreas when a large dose is given.     

Control of cyclic AMP accumulation in dog acini: its relation to amylase release

In dispersed acini from dog pancreas, exogenous derivatives of cAMP stimulated the amylase release; 8-Br-cAMP was a more potent stimulant than Bt2-cAMP, and induced a potentiation of the amylase release stimulated by cerulein. Both secretin and vasoactive intestinal peptide (VIP), increased cellular cAMP, with a greater potency for secretin, and supramaximal concentration of secretin plus VIP increased cellular cAMP to the same degree as that obtained with secretin alone. 125I-VIP-binding studies showed that in dog pancreatic acini there is a 95% decrease in the number of VIP-preferring receptors with minor changes in receptor affinity as compared to guinea-pig pancreas. The absence of effect between secretin or VIP and cerulein in stimulating amylase release could likely be explained by the low number in VIP-preferring receptors on dog pancreatic acini.     

Effect of diabetes mellitus on pancreatic exocrine secretion from isolated perfused pancreas in rats

We studied pancreatic exocrine function in response to cerulein and carbamylcholine in isolated perfused pancreas obtained from control, streptozotocin-induced diabetic, and insulin-treated diabetic rats. The time course of pancreatic juice, protein, amylase, and trypsinogen secretion in response to cerulein or carbamylcholine in diabetic rats was similar to that in control rats. Basal as well as cerulein- or carbamylcholine-stimulated output of amylase from diabetic rat pancreas was significantly reduced, whereas that of trypsinogen was similar to the control. Amylase and trypsinogen outputs in response to 620 pM (1.0 ng/ml) cerulein from insulin-treated diabetic rat pancreas were significantly lower than those from control rat pancreas, although the pancreatic contents of these enzymes were similar to or greater than those in control rats. The dose-response curves of pancreatic juice, protein, amylase, and trypsinogen for cerulein and carbamylcholine were biphasic in both control and diabetic rats. The minimal and the maximal release in response to cerulein occurred with higher concentrations in diabetic rats compared with control rats. In contrast, the maximal responses were obtained with 1 M carbamyl-choline in control rats and with 0.1–1 M carbamylcholine in diabetic rats. The present study demonstrates that the concentration of cerulein required to elicit maximal response was increased, whereas that to carbamylcholine was reduced in diabetic rat pancreas, and that the protein and enzyme outputs in response to cerulein were significantly reduced in insulin-treated diabetic rat pancreas despite restoration of the pancreatic enzyme contents to control levels.     

Beneficial effects of the synthetic trypsin inhibitor camostate in cerulein-induced acute pancreatitis in rats

The therapeutic effect and the mechanism of action of the synthetic trypsin inhibitor camostate were studied in a rat model of acute interstitial pancreatitis induced by four subcutaneous injections of 20 g/kg body weight of cerulein at hourly intervals. Rats with acute pancreatitis were given either 100 mg/kg body weight camostate or volume- and pH-adjusted water via an orogastric tube 30 min after the last cerulein injection. The elevation of serum amylase activity was significantly reduced by camostate treatment and the peak value was seen 1 hr earlier than that observed in the rats that did not receive camostate. Camostate also inhibited the reduction in pancreatic content of lipase and amylase seen during experimental pancreatitis. These effects were accompanied by alleviation of the histologic signs of acute pancreatitis such as cellular infiltration and acinar cell vacuolization. After oral administration, camostate and its metabolite were absorbed from the intestine and were detectable in plasma for more than 6 hr in concentrations high enough to have antiprotease activity. In addition, camostate in the duodenum was able to increase pancreatic juice flow and protein output and to stimulate endogenous secretin release. These results suggest that oral administration of camostate reduces the severity of cerulein-induced acute pancreatitis by releasing endogenous secretin and by its antiprotease activity.This work was supported in part by a grant from the Japanese Ministry of Health and Welfare (Intractable Disease of the Pancreas).     

Nitric oxide modulates pancreatic basal secretion and response to cerulein in the rat: Effects in acute pancreatitis

Nitric oxide synthase activity is detected in the pancreas, but the role of NO on pancreatic function has not been fully characterized. The aim of this study was to evaluate the role of NO in normal and diseased pancreatic function. Amylase and NO secretion were measured in vivo in rats and in vitro in dispersed acini, with and without NO synthesis blockade, by N^G-nitro-l-arginine methyl ester (l-NAME). Rats were subjected to cerulein-induced pancreatitis, and the effects of l-NAME or NO donors were assessed. l-NAME reduced amylase output to 60% of basal. This effect was reversed by l-arginine. The secretory response to optimal doses of cerulein induced a poor amylase secretion and a marked release of NO. High doses of cerulein in combination with l-NAME inhibited NO formation and amylase secretion. In dispersed acini, supramaximal cerulein concentrations induced NO release, but the amylase dose-response curve was not modified by NO inhibition. In acute pancreatitis, l-NAME increased amylasemia and tissue myeloperoxidase activities, whereas NO donors reduced amylasemia, lipasemia, and the histological damage score. The l-arginine/NO pathway facilitates basal and stimulated pancreatic secretion in vivo. NO donor drugs may improve the course of acute pancreatitis.     

Time-dependent effects of maximal doses of cerulein on the secretory response of the rat pancreas

The present study was performed to determine the time-dependent effects of chronic administration of maximal doses of cerulein on the secretory function of the rat pancreas. Four groups of rats, one treated with 0.9% NaCl (control) and the others with cerulein (2, 5, and 10 μg/kg twice a day ip, respectively) were used. After a treatment period of 15, 30, or 60 d, eight rats were taken from each group, the pancreatic bile duct was surgically cannulated, and the pancreatic juice was collected after CCK or secretin stimulation. Then the rats were killed and the pancreas was removed and weighed. Administration of 2 μg/kg of cerulein for 15 d induced a significant increase (p<0.05) in the volume of pancreatic juice in response to hormonal stimulation. The enzyme and bicarbonate outputs increased only in response to CCK, not to secretin. The above-mentioned increases are significant only when related to body weight, not to pancreatic weight. There was good correlation between pancreatic weight and the increase in the secretory parameters. The secretion pattern was not significantly modified by higher doses of cerulein nor by longer duration of treatment. We conclude that 1) increase in pancreatic secretory function induced by 2 μg/kg of cerulein is not enhanced by higher doses of peptide and 2) the functional capacity of the acinar cells is not affected by the length of treatment. These data are of interest as experimental backing to therapeutic use of CCK-like peptides in pancreatic exocrine insufficiency.     

Fasting prevents acute pancreatitis induced by cerulein in rats

We examined the effect of fasting on the course of experimental acute pancreatitis induced in rats by four subcutaneous injections of 20 g/kg body weight of cerulein at hourly intervals. Rats were either fasted from 24 hr before to 9 hr after the first cerulein injection or fed ad libitumthroughout the experiment. Twenty-four hours of fasting reduced cerulein-induced increases in serum levels of amylase and anionic trypsin(ogen) to 50 and 70% of those in fed rats, respectively. Increases in pancreatic wet weight after cerulein injections were also less in fasted rats than in fed rats. Pancreatic content of trypsin was significantly decreased after a 24-hr fast, and no further changes were induced by cerulein injections. The histological signs of acute pancreatitis were greatly alleviated by fasting. However, 24 hr of fasting did not alter the sensitivity and responsiveness of the exocrine pancreas to cerulein in both in vivoand in vitro.Plasma CCK bioactivity and immunoreactive secretin concentration in 24-hr-fasted rats were significantly lower than those in fed rats. Administration of CCK receptor antagonist, loxiglumide, 12 hr prior to the induction of acute pancreatitis reduced the increase in serum amylase activity in fed rats to nearly the same levels as that in fasted rats and alleviated histological signs of pancreatitis to some extent. These present observations suggest that fasting lessens the severity of cerulein-induced acute pancreatitis by reducing endogenous CCK release.This work was supported in part by a grant from the Japanese Ministry of Health and Welfare and Grant-in-Aid for Scientific Research (C).     

Potentiating effect of CCK and secretin on rat exocrine pancreas and its cholinergic dependence.

We investigated whether physiological doses of cholecystokinin (CCK) potentiate the stimulating effect of a physiological dose of secretin on exocrine pancreatic secretion, and the effect of atropine on this potentiating action in rats. Pure pancreatic juice was collected from anesthetized rats prepared by pancreatic duct and bile duct cannulation. Intravenous infusion of CCK-8 in three different doses, 0.03, 0.06, and 0.12 micrograms/kg/h, significantly increased pancreatic juice volume and amylase output, dose-dependently. Simultaneous infusion of CCK-8 in graded doses with secretin in a dose of 0.03 CU/kg/h, produced a dose-related increase in pancreatic secretory response significantly greater than the response to CCK-8 alone (p less than 0.05) and greater than the sum of the response to secretin alone and CCK-8 alone. The incremental pancreatic secretion, including juice volume and amylase output, in response to intravenous infusion of CCK-8 with secretin, was significantly suppressed by intravenous administration of atropine in a dose of 100 micrograms/kg/h (p less than 0.01). Thus, it is concluded that CCK-8 and secretin in physiological doses potentiate each other's stimulatory action on exocrine pancreatic secretion and this potentiating action appears to be cholinergic-dependent.     

Melatonin Reduces Lipid Peroxidation and Tissue Edema in Cerulein-Induced Acute Pancreatitis in Rats

Since oxygen free radicals and lipidperoxidation have been implicated in the pathogenesis ofan early stage of acute pancreatitis, we examinedwhether melatonin, a recently discovered free-radicalscavenger, could attenuate pancreatic injury inSprague-Dawley rats with cerulein-induced pancreatitis.Acute pancreatitis was induced by four intraperitonealinjections of cerulein (50 g/kg body wt) given at1-hr intervals. Thirty minutes after the lastcerulein injection, the rats were killed and the degreeof pancreatic edema, the level of lipid peroxidation inthe pancreas, and serum amylase activity were increased significantly. Pretreatment with melatonin (10or 50 mg/kg body wt) 30 min before each ceruleininjection resulted in a significant reduction inpancreatic edema and the levels of lipid peroxidation.Serum amylase activity, however, was notsignificantly influenced by either dose of melatonin.Moreover, we found that cerulein administration wasassociated with stomach edema as well as high levels oflipid peroxidation in the stomach and smallintestine, which were also reduced by melatonin.Melatonin's protective effects in cerulein-treated ratspresumably relate to its radical scavenging ability andto other antioxidative processes induced bymelatonin.     

Effects of tetraprenylacetone on pancreatic exocrine secretion and acute pancreatitis in two experimental models in rats

Summary 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.     

Somatostatin analog, SMS 201-995, inhibits pancreatic exocrine secretion and release of secretin and cholecystokinin in rats.

We studied the effect of a synthetic octapeptide somatostatin analog, SMS 201-995 (sandostatin), on pancreatic exocrine secretion and on plasma secretin and cholecystokinin (CCK) levels in vivo in anesthetized rats. The exocrine pancreas was stimulated by either intravenous infusion of both secretin (0.06 CU/kg/h) and cholecystokinin octapeptide (CCK-8) (0.03 micrograms/kg/h) or intraduodenal infusion of oleic acid (pH 6.5) in a dose of 0.25 mmol/h. Intravenous administration of SMS 201-995 in three different doses of 100, 200, and 400 ng/kg/h resulted in dose-related inhibition of pancreatic secretion in terms of volume, bicarbonate, and amylase stimulated by exogenous secretin and CCK. Intraduodenal oleic acid stimulated pancreatic secretion, including volume, bicarbonate, and amylase, and this was accompanied by a significant elevation in the plasma concentrations of secretin and CCK. Intravenous administration of SMS 201-995 in the three different doses described above caused dose-dependent suppression of the increase in pancreatic exocrine secretion as well as the plasma concentration of secretin and CCK induced by intraduodenal infusion of oleic acid. It is concluded that SMS 201-995 inhibits pancreatic exocrine secretion and the release of endogenous hormones, such as secretin and CCK, in rats.     

Pancreatic secretory responses to long-term infusions of secretin and cerulein in humans.

We measured pancreatic enzyme and bicarbonate responses to graded doses of intravenous secretin or cerulein alone or together in healthy human subjects. Bicarbonate responses were steady and well maintained during the last 3.5 h of the 4 h of infusions of secretagogues, giving evidence for a constant pancreatic flow rate. Potentiation (more-than-additive response) was observed between secretin and cerulein for bicarbonate secretion, but not for enzyme secretion. Secretin stimulated pancreatic enzyme secretion. The effect was most pronounced with amylase secretion and less prominent with lipase, trypsin, and chymotrypsin secretion. Changes in the proportion of enzymes were seen over time, with trypsin and chymotrypsin output declining towards the end of cerulein infusion. We conclude that in humans the effects of secretin on pancreatic enzyme secretion are complex and include time-dependent changes in the enzyme mixture, but potentiation between secretin and cerulein does not occur for enzyme output.     

Mechanism of pancreatic hypersecretion in dogs with obstructive jaundice

Pancreatic exocrine function in experimental obstructive jaundice was examined using dogs. Outputs of pancreatic juice, bicarbonate and amylase were greater in dogs with obstructive jaundice than in control dogs. To further examine the hypersecretory mechanism in obstructive jaundice, we examined pancreatic exocrine secretion stimulated by secretin and pancreozymin in both the isolated perfused pancreas and pancreatic dispersed cell culture. The perfused pancreas stimulated with secretin and pancreozymin in dogs with obstructive jaundice showed higher secretion of volume, bicarbonate and amylase than in control dogs. Dispersed pancreatic cells of jaundiced dogs stimulated by secretin and pancreozymin released more bicarbonate and amylase into the media than dispersed cells of control dogs. These data suggest pancreatic hypersecretion in obstructive jaundice is not due to excessive serum levels of secretin and pancreozymin or impaired metabolism of these hormones.     

Plasma osmolality and exocrine pancreatic secretion

To confirm the influence of plasma osmolality on exocrine pancreatic secretion, hypertonic saline (4% saline) was given intravenously to dogs with gastric and pancreatic fistulae. Intravenous administration of hypertonic saline caused a reduction of pancreatic juice flow and bicarbonate output, but did not alter protein output stimulated by secretin and cerulein. The changes of pancreatic juice flow(X) exhibited negative correlations with the changes in plasma osmolality(Y)(Y = -2.2X + 6A, r = -0.74,p < 0.01). Plasma osmolality and plasma vasopressin level were measured simultaneously. Plasma osmolality was elevated from 292 to 315 mOsm/kg with concurrent increase of plasma vasopressin level from 2.4 to 19.6 pg/ mL. On the other hand, exogenous administration of vasopressin inhibited pancreatic juice flow and bicarbonate output dose-dependently. In conclusion, elevation of plasma osmolality decreased exocrine pancreatic secretion stimulated by secretin and cerulein, and vasopressin may play an important role in its mechanism.     

Mechanism of pancreatic hypersecretion in dogs with obstructive jaundice

Summary Pancreatic exocrine function in experimental obstructive jaundice was examined using dogs. Outputs of pancreatic juice, bicarbonate and amylase were greater in dogs with obstructive jaundice than in control dogs. To further examine the hypersecretory mechanism in obstructive jaundice, we examined pancreatic exocrine secretion stimulated by secretin and pancreozymin in both the isolated perfused pancreas and pancreatic dispersed cell culture. The perfused pancreas stimulated with secretin and pancreozymin in dogs with obstructive jaundice showed higher secretion of volume, bicarbonate and amylase than in control dogs. Dispersed pancreatic cells of jaundiced dogs stimulated by secretin and pancreozymin released more bicarbonate and amylase into the media than dispersed cells of control dogs. These data suggest pancreatic hypersecretion in obstructive jaundice is not due to excessive serum levels of secretin and pancreozymin or impaired metabolism of these hormones.     

A small dose of somatostatin inhibits the secretin stimulated secretion of bicarbonate, amylase, and chymotrypsin in man

The effects of a small dose of somatostatin (0.025 mg/h) on the pancreatic secretion of bicarbonate, amylase, and chymotrypsin during stepwise increasing doses of secretin was examined in six healthy volunteers. The secretion of bicarbonate, amylase, and chymotrypsin in response to secretin was significantly reduced by somatostatin. Both output and concentration of pancreatic enzymes were reduced, whereas the concentration of bicarbonate remained unchanged. The pattern of inhibition suggests that somatostatin is a competitive inhibitor of secretin in the stimulation of pancreatic secretion of bicarbonate, which supports the hypothesis of a direct effect of somatostatin on the exocrine secretory cells of the pancreas. The pattern of inhibition of amylase and chymotrypsin secretion is different and difficult to interpret from the present study, but somatostatin may inhibit also the secretin stimulated pancreatic secretion of enzymes completely, as the inhibitory effect seemed to decline when larger doses of secretin were applied.     

Protective effects of rhubarb on experimental severe acute pancreatitis

AIM: To investigate the effects of rhubarb on severe acute pancreatitis (SAP) in rats. METHODS: Severe acute pancreatitis was induced by two intraperitoneal injections of cerulein (40 μg/kg body weight) plus 5-h restraint water-immersion stress. Rhubarb (75-150 mg/kg) was orally fed before the first cerulein injection. The degree of pancreatic edema, serum amylase level, local pancreatic blood flow (PBF), and histological alterations were investigated. The effects of rhubarb on pancreatic exocrine secretion in this model were evaluated by comparing with those of somatostatin. RESULTS: In the Cerulein+Stress group, severe edema and diffuse hemorrhage in the pancreas were observed, the pancreatic wet weight (11.60&#177;0.61 g/Kg) and serum amylase (458 490&#177;43 100 U/L) were markedly increased (P&lt;0.01 vs control). In the rhubarb (150 mg/kg) treated rats, necrosis and polymorphonuclear neutrophil (PMN) infiltration in the pancreas were significantly reduced (P&lt;0.01), and a marked decrease (50%) in serum amylase levels was also observed (P&lt;0.01). PBF dropped to 38% (93&#177;5 mL/min per 100 g) of the control in the Cerulein+Stress group and partly recovered in the Cerulein+Stress+Rhubarb 150 mg group (135&#177;12 mL/min per 100 g) (P&lt;0.01). The pancreatic exocrine function was impaired in the SAP rats. The amylase levels of pancreatic juice were reduced in the rats treated with rhubarb or somatostatin, comparing with that of untreated SAP group. The bicarbonate concentration of pancreatic juice was markedly elevated only in the rhubarbtreated group (P&lt;0.01). CONCLUSION: Rhubarb can exert protective effects on SAP, probably by inhibiting the inflammation of pancreas, improving pancreatic microcirculation, and altering exocrine secretion.     

Manifestations of experimental acute pancreatitis in young and old rats

Two kinds of experimental pancreatitis were induced in young (4-6 month) and old (25-27 month) female Wistar rats: acute edematous pancreatitis was induced by intraperitoneal administration of a high dose of cerulein (40 micro/kg x 2) and acute hemorrhagic pancreatitis was intraductal injection of 1% deoxycholic acid. After these treatments, the plasma amylase concentration and pancreatic wet weight were determined and the pancreas was examined histologically. In the groups with cerulein induced pancreatitis one of eight old rats died, whereas all five young rats survived. There was no specific finding macroscopically in the liver, kidney, lung or heart of old rats at autopsy after cerulein injection. The plasma amylase concentration and the pancreatic wet weight were significantly increased by administration of cerulein or deoxycholic acid in both young and old rats. There was no significant difference in the plasma amylase concentrations in young and old rats after the induction of acute pancreatitis. The increase in pancreatic wet weight was less in old rats than in young ones after deoxycholic acid treatment, but similar in the two groups after cerulein injection. The extents of histological changes were also similar in young and old rats. Thus, no evidence that aging increases susceptibility to pancreatitis was obtained.     

Glucagon inhibition of cerulein-induced hypertrophy of the exocrine pancreas

Glucagon is structurally related to secretin but inhibits the effects of secretin and cholecystokinin (CCK) on pancreatic secretion in vivo. Because secretin is a weak stimulant of pancreatic growth and potentiates the trophic effects of CCK, we hypothesized that glucagon might inhibit CCK-induced pancreatic growth. Four groups of 10 rats were injected with saline, glucagon (30 micrograms/kg, equimolar to a known trophic dose of secretin), cerulein (0.67 microgram/kg), or glucagon plus cerulein every 8 h for 5 days. The pancreas was excised, weighed, and assayed for total content of DNA, protein, amylase, chymotrypsinogen, and lipase. In control and glucagon-alone groups, the small intestine was also removed, weighed, and assayed for DNA, protein, and disaccharidase content. Glucagon alone decreased pancreatic DNA and increased lipase content. Compared with cerulein-treated animals, animals treated with glucagon and cerulein showed significant decreases in pancreatic weight and content of protein, amylase, and chymotrypsinogen. Although glucagon had significant effects on intestinal protein, maltase, and sucrase contents in certain segments, there was no clear pattern of response. The data suggest that glucagon may be an inhibitory regulator of pancreatic growth, acting to block the effects of CCK on pancreatic hypertrophy.     

Immunoglobulin A Secretion into Pancreatic Juice as a Novel Marker of Local Immune Defense and Exocrine Pancreatic Function

The importance of secretory immunoglobulin A (IgA) of local immune defense in the gastrointestinal tract has gained increasing acceptance. Bacterial contamination is a major factor related to mortality in acute pancreatitis. However, very little is known about IgA in pancreatic juice. Pure pancreatic juice was collected from 40 patients undergoing pancreatoduodenectomy. The patients were divided into three groups according to the degree of preoperative pancreatic duct obstruction, as follows: normal, narrowed, and obstructed. IgA concentration, amylase activity, and daily volume of pancreatic juice were measured. Daily IgA secretion into pancreatic juice was constant during the early period after the operation. The concentration of IgA in the control group was 5 ± 0.8 g/ml, and IgA daily secretion was 1.2 ± 0.2 mg/day. Pancreatic duct obstruction resulted in a marked decrease in both amylase and pancreatic juice secretion. The concentration of IgA, however, was markedly increased in the narrowed group (11.1 ± 2.4 g/ml) and the obstructed group (32.5 ± 5.4 g/ml). The concentration of amylase increased with the increase in pancreatic juice. Conversely, the concentration of IgA increased with the decrease in volume of pancreatic juice. Similarly, the increased in IgA concentrations positively correlated with the decrease in amylase activity. In conclusion, the mechanisms that modulate IgA secretion in the human pancreas are essentially different from those that modulate digestive enzyme and fluid secretion. IgA in pancreatic juice may play an important role in pathological conditions such as pancreatic duct obstruction. As such, the measurement of IgA in pancreatic juice may potentially be used as a new marker of local immune defense and exocrine pancreatic function.