Pancreatic Amylase Output Research Articles

Effect of osteocalcin on human beta cell proliferation and function and its role on insulin secretion

Effect of osteocalcin on human beta cell proliferation and function and its role on insulin secretion

Roles of Non-cholinergic Intrapancreatic Nerves, Serotonergic Nerves, on Pancreatic Exocrine Secretion in the Isolated Perfused Rat Pancreas

It has been rereported that axons which display 5-hydroxytryptamine (5-HT) immunoreactivity are abundant in the pancreas and the majority of serotonergic axons terminate within intrapancreatic ganglia, islet and acini. This histological result strongly suggests that intrapancreatic serotonergic nerves could affect to the pancreatic endocrine and exocrine secretion. Thus, this study was aimed to investigate whether intrapancreatic serotonergic nerves could affect pancreatic exocrine secretion and an action mechanism of the intrapancreatic serotonergic nerves. The rats were anesthetized with a single injection of urethane. The median line and the abdominal aorta was carefully dissected and cannulated with PE-50 tubing just above the celiac artery, and then tightly ligated just below the superior mesenteric artery. The pancreatic duct was also cannulated with Tygon microbore tubing. With the addition of serotonin, pancreatic volume flow and amylase output were significantly inhibited electrical field stimulation (EFS). On the other hand, pancreatic volume flow and amylase output were significantly elevated in EFS with the addition of spiperone. EFS application, however, pancreatic volume flow and amylase output had no significant change in cholecystokinin (CCK) alone when serotonin was applied under a 5.6 mM glucose background. Pancreatic volume flow and amylase output under 18 mM glucose background were significantly elevated in CCK plus serotonin than in CCK alone. These data suggest that intrapancreatic serotonergic nerves play an inhibitory role in pancreatic exocrine secretion and an important role in the insulin action or release.

The effect of luminal ghrelin on pancreatic enzyme secretion in the rat

Ghrelin, a 28-amino-acid peptide produced predominantly by oxyntic mucosa has been reported to affect the pancreatic exocrine function but the mechanism of its secretory action is not clear. The effects of intraduodenal (i.d.) infusion of ghrelin on pancreatic amylase outputs under basal conditions and following the stimulation of pancreatic secretion with diversion of pancreato-biliary juice (DPBJ) as well as the role of vagal nerve, sensory fibers and CCK in this process were determined. Ghrelin given into the duodenum of healthy rats at doses of 1.0 or 10.0 μg/kg increased pancreatic amylase outputs under basal conditions or following the stimulation of pancreatic secretion with DPBJ. Bilateral vagotomy as well as capsaicin deactivation of sensory fibers completely abolished all stimulatory effects of luminal ghrelin on pancreatic exocrine function. Pretreatment with lorglumide, a CCK 1 receptor blocker, reversed the stimulation of amylase release produced by intraduodenal application of ghrelin. Intraduodenal ghrelin at doses of 1.0 or 10.0 μg/kg increased plasma concentrations of CCK and ghrelin. In conclusion, ghrelin given into the duodenum stimulates pancreatic enzyme secretion. Activation of vagal reflexes and CCK release as well as central mechanisms could be implicated in the stimulatory effect of luminal ghrelin on the pancreatic exocrine functions.

Pathophysiology of alcohol-induced pancreatic injury.

The evidence that ethanol abuse can lead to pancreatitis is overwhelming, but the mechanism(s) by which ethanol causes pancreatic injury and pancreatitis are not known. Many studies have focused on short-term effects of ethanol administration on exocrine pancreatic function, but the results reported have been variable and no clear picture has emerged. Attempts to induce pancreatitis by long-term ethanol administration have, for the most part, failed. We evaluated the effects of ethanol administration on pancreatic secretion of digestive enzymes. These studies indicate that administration of ethanol results in a transient increase in pancreatic amylase output and plasma cholecystokinin (CCK) levels. This phenomenon is mediated by a trypsin-sensitive CCK-releasing factor that is present within the duodenal lumen. These observations lead us to speculate that repeated CCK-mediated, ethanol-induced stimulation of pancreatic digestive enzyme secretion may play a role in the events that link ethanol abuse to the development of pancreatic injury.

Effect of cholecystokinin1 receptor antagonist loxiglumide (CR1505) on basal pancreatic exocrine secretion in conscious rats.

To examine the involvement of cholecystokinin (CCK) in the basal pancreatic exocrine, we investigated the effect of loxiglumide (CR1505), a CCK1 receptor antagonist, on basal pancreatic exocrine secretion in conscious rats. After the basal collection of pancreatic juice for 1 hour, loxiglumide (10 mg/kg/h) or saline was infused via the femoral vein continuously for 2 hours. Loxiglumide significantly suppressed the basal pancreatic protein and amylase outputs. However, loxiglumide did not alter the basal pancreatic juice volume. These results demonstrate that loxiglumide suppresses basal pancreatic exocrine secretion in normal rats. They also suggest that CCK is involved in basal pancreatic exocrine in conscious rats and that loxiglumide may be useful as a therapeutic agent for pancreatitis, even during fasting, by attenuating the basal pancreatic exocrine burden on the pancreas.

Response of Rat Exocrine Pancreas to High-Fat and High-Carbohydrate Diets

Intake of diets with high fat content is a risk factor for acute pancreatitis and pancreatic cancer. The underlying mechanisms leading to the development of these diseases due to high fat intake are currently unknown. The current study was designed in rats to determine the physiologic and pathological consequences of a highfat diet that contained excess amounts of cottonseed oil or a high-carbohydrate diet that contained high amounts of sucrose on the exocrine pancreas. Rats were maintained on the diets for 4 weeks, and a cannula was inserted into the right jugular vein and one into the pancreatic duct for collection of pancreatic juice. Volume of the pancreatic juice and concentrations of amylase, lipase, and trypsinogen in the pancreatic juice were measured before and after infusions of CCK-8. Results showed that basal and CCK-stimulated pancreatic outputs of volume, amylase and lipase but not trypsinogen, were significantly elevated in intact rats given a high-fat diet when compared with rats given a high-carbohydrate diet. Forty-eight hours later, rats were sacrificed, and parts of the pancreas were removed for isolation of pancreatic acinar cells and for histopathologic studies. Pancreatic acini isolated from rats on a high-fat diet showed significantly lower basal and CCK-stimulated amylase release when compared with those on a high-carbohydrate diet. Histology of the pancreas of rats on a high-carbohydrate diet appeared normal; however, the pancreas of rats on high-fat diet showed significant alterations in exocrine pancreas. These results showed abnormalities in the exocrine pancreas of rats on a high-fat diet, that were not found in rats on a high-carbohydrate diet; further, they support the contention that a high-fat diet has a deleterious effect on the pancreas.

Response of Rat Exocrine Pancreas to High‐Fat and High‐Carbohydrate Diets

Abstract. Intake of diets with high fat content is a risk factor for acute pancreatitis and pancreatic cancer. The underlying mechanisms leading to the development of these diseases due to high fat intake are currently unknown. The current study was designed in rats to determine the physiologic and pathological consequences of a high‐fat diet that contained excess amounts of cottonseed oil or a high‐carbohydrate diet that contained high amounts of sucrose on the exocrine pancreas. Rats were maintained on the diets for 4 weeks, and a cannula was inserted into the right jugular vein and one into the pancreatic duct for collection of pancreatic juice. Volume of the pancreatic juice and concentrations of amylase, lipase, and trypsinogen in the pancreatic juice were measured before and after infusions of CCK‐8. Results showed that basal and CCK‐stimulated pancreatic outputs of volume, amylase and lipase but not trypsinogen, were significantly elevated in intact rats given a high‐fat diet when compared with rats given a high‐carbohydrate diet. Forty‐eight hours later, rats were sacrificed, and parts of the pancreas were removed for isolation of pancreatic acinar cells and for histopathologic studies. Pancreatic acini isolated from rats on a high‐fat diet showed significantly lower basal and CCK‐stimulated amylase release when compared with those on a high‐carbohydrate diet. Histology of the pancreas of rats on a high‐carbohydrate diet appeared normal; however, the pancreas of rats on high‐fat diet showed significant alterations in exocrine pancreas. These results showed abnormalities in the exocrine pancreas of rats on a high‐fat diet, that were not found in rats on a high‐carbohydrate diet; further, they support the contention that a high‐fat diet has a deleterious effect on the pancreas.

Elevation of plasma peptide YY and pancreatic juice hypersecretion following massive small bowel resection in the rat.

To clarify a physiological role of endogenous peptide YY(PYY) on pancreatic exocrine secretion, gastrointestinal transit and bile flow, a hyper-PYY-emia model was constructed by performing a massive small bowel resection using rats. (1) 75% resection of the small intestine was performed at its distal side. Two weeks after surgery, these rats were fed a liquid meal, and intestinal transit of contents was observed and plasma PYY and secretin concentrations were measured by radioimmunoassay. (2) Two weeks after the same surgery, a liquid meal was infused into the duodenum, and both pancreatic juice and bile were collected separately under general anesthesia. Transit of the intestinal contents from the pyloric ring, plasma CCK concentrations, pancreatic juice flow, amylase output, and bile flow were determined. Hyper-PYY-emia occurred following surgery both at fasting and after feeding, accompanied by retardation of gastrointestinal transit, increase of pancreatic juice flow and decrease of bile flow. Plasma secretin levels were elevated slightly, while CCK levels remained unchanged. In conclusion, massive small bowel resection is a useful model to induce hyper-PYY-emia in rats. It is considered that, in a malnutritional state after small intestinal resection, a colonic regulatory mechanism, via humoral factors such as PYY, participates in the feedback regulation of proximal intestinal as well as of pancreatic function.

A cholecystokinin-releasing factor mediates ethanol-induced stimulation of rat pancreatic secretion.

The mechanisms by which short-term ethanol administration alters pancreatic exocrine function are unknown. We have evaluated the effects of ethanol administration on pancreatic secretion of digestive enzymes. In our studies, anesthetized as well as conscious rats were given ethanol at a rate sufficient to cause the blood ethanol concentration to reach levels associated with clinical intoxication. Ethanol was administered over a 2-h period during which blood ethanol levels remained stably elevated. We report that intravenous administration of ethanol results in a transient increase in pancreatic amylase output and plasma cholecystokinin (CCK) levels. The ethanol-induced increase in amylase output can be completely inhibited by the CCK-A receptor antagonist L-364,718 and partially inhibited by the muscarinic cholinergic antagonist atropine. The ethanol-induced rise in amylase output can be completely prevented by instillation of trypsin into the duodenum or by lavage of the duodenum with saline during ethanol administration. Furthermore, the intraduodenal activity of a CCK-releasing factor is increased by infusion of ethanol. These studies indicate that administration of ethanol causes rat pancreatic exocrine secretion to increase. This phenomenon is mediated by a trypsin-sensitive CCK-releasing factor which is present within the duodenal lumen. These observations lead us to speculate that repeated CCK-mediated ethanol-induced stimulation of pancreatic digestive enzyme secretion may play a role in the events which link ethanol abuse to the development of pancreatic injury.

Effect of pituitary adenylate cyclase-activating polypeptide on exocrine and endocrine secretion in the ovine pancreas

The role of pituitary adenylate cyclase-activating polypeptide (PACAP) in the regulation of exocrine and endocrine pancreas was investigated in conscious sheep. Intravenous infusions of PACAP-27 and PACAP-38 (1, 3, and 10 pmol/kg/min) for 10 min during phase II of the duodenal migrating myoelectric complex accelerated pancreatic protein and amylase outputs dose-dependently. The responses in enzyme secretion to both PACAPs at the highest doses were inhibited significantly by atropine infusion (14.4 nmol/kg/min). Vasoactive intestinal polypeptide (VIP) at 3 pmol/kg/min significantly accelerated protein but not amylase outputs, although the response to the highest dose was not significantly influenced by atropine. PACAP-27 and VIP increased pancreatic juice flow and bicarbonate output dose-dependently; however, the responses to the highest dose were not altered significantly by atropine. On the other hand, intravenous injection of PACAP-38 (100 pmol/kg) did not influence basal plasma concentration of insulin, glucagon, and glucose. Moreover, PACAP-38 (1–100 pmol/kg) altered neither pancreatic endocrine response to intravenous infusion of glucose (20 μmol/kg/min) nor that to n-butyric acid (33 μmol/kg/min). These results suggest that PACAP contributes to the regulation of exocrine secretion of the ovine pancreas but not to endocrine secretion. PACAP appears to accelerate pancreatic enzyme secretion mostly via the cholinergic nerves.

Effects of KSG-504, a New Cholecystokinin-A-Receptor Antagonist, on Pancreatic Exocrine and Endocrine Secretions in Rats

The effects of KSG-504 ((S)-arginium (R)-4-[N-(3-methoxypropyl)-N-pentylcarbamoyl]-5-(2-naphthylsulf onyl) pentanoate monohydrate), a new cholecystokinin (CCK)-A-receptor antagonist, on pancreatic exocrine secretion in anesthetized rats and endocrine secretion in conscious rats were studied. Intravenous injection of KSG-504 inhibited the pancreatic amylase output stimulated by intravenous infusion of CCK-8 in a dose-dependent manner (ED50: 18 micrograms/kg/min). Moreover, KSG-504 significantly reduced the CCK-8-stimulated increases in pancreatic juice volume and outputs of protein, trypsin and lipase. Intraduodenal infusion of casein increased the plasma CCK concentration and the pancreatic amylase output. KSG-504 significantly inhibited the pancreatic amylase output stimulated by casein. Pancreatic juice volume and bicarbonate output were significantly stimulated by intravenous infusion of secretin, but were not changed by KSG-504. When pancreatic exocrine secretion was stimulated by secretin plus CCK-8, KSG-504 suppressed the increases in juice volume and bicarbonate output to the level stimulated by secretin alone. Basal pancreatic amylase output was decreased by KSG-504. KSG-504 decreased the level of plasma immunoreactive insulin (IRI) stimulated by glucose plus CCK-8, but had no effect on IRI stimulated by glucose alone and the basal IRI. These in vivo studies suggest that KSG-504 has significant inhibitory effects both on the pancreatic exocrine and endocrine secretion stimulated by CCK, but has no effect on the exocrine secretion stimulated by secretin.

The role of insulin in the interaction of secretin and cholecystokinin in exocrine secretion of the isolated perfused rat pancreas.

To investigate the role of insulin in the potentiation effect of secretin and cholecystokinin (CCK) on pancreatic exocrine secretion, the pancreas was isolated from rats and perfused with modified Krebs-Henseleit solution containing glucose at three concentrations. Intraarterial glucose at concentrations of 2.5, 10, and 25 mM produced modest but significant increases in both the pancreatic flow rate and the amylase output in a concentration-dependent manner. The mixture of secretin and CCK at concentrations of 18.5 and 14 pM, respectively, added to the glucose solutions augmented the pancreatic flow rate and amylase output in relation to the glucose concentration. In the streptozotocin-treated pancreas, the mixture of secretin and CCK failed to augment the pancreatic exocrine secretion unless exogenous insulin was added to the perfusate. Secretin markedly potentiated the CCK-induced amylase output when insulin was present in the circulation. However, CCK did not potentiate the secretin-induced flow rate even if insulin was present in the circulation. Insulin did not affect the actions of secretin alone but it potentiated the actions of CCK alone in both the pancreatic flow rate and the amylase output. It is concluded from the above results that insulin intensifies the combined actions of secretin and CCK in pancreatic exocrine secretion by potentiating the CCK action. Furthermore, in the presence of insulin, secretin is able to potentiate the pancreatic enzyme secretion stimulated by CCK.

Effect of a Novel Cholecystokinin Receptor Antagonist, FK480, Administered Intraduodenally, on Pancreatic Secretion in Rats

The effect of a new cholecystokinin (CCK)-A receptor antagonist, FK480, developed in Japan, on pancreatic exocrine secretion stimulated by exogenous CCK and intraduodenal casein was investigated in vivo when administered to anesthetized rats intraduodenally, and its CCK antagonistic activity was compared with that of CR 1505. Intraduodenal administration of FK480 at graded doses of 0.0016-1.0 mg/kg-h produced dose-dependent inhibition of pancreatic juice volume and amylase output stimulated by intravenous infusion of CCK-8 at a dose of 0.06 micrograms/kg-h. The half-maximal inhibitory dose (ID50) of FK480 for CCK-8-stimulated amylase secretion was 0.025 mg/kg-h, whereas the ID50 of CR 1505 was 5.2 mg/kg-h, indicating that FK480 is 208 times more potent than CR 1505. Moreover, intraduodenal FK480 (0.2 mg/kg-h) significantly suppressed pancreatic juice volume and amylase output augmented by intraduodenal infusion of casein (400 mg/h). It is concluded that FK480 administered intraduodenally has a significant, potent inhibitory action on the exocrine pancreas stimulated by exogenous CCK and intraduodenal casein.

A New CCK-A Antagonist, KSG-504, Administered Intraduodenally, Inhibits Pancreatic Secretion in Rats

We studied the effect in anesthetized rats of a new cholecystokinin (CCK) receptor antagonist developed in Japan, KSG-504, administered intraduodenally, on pancreatic exocrine secretion stimulated by exogenous CCK and intraduodenal casein. Intraduodenal administration of KSG-504 in graded doses of 2.5-50 mg/kg/h produced dose-dependent inhibition of pancreatic juice volume and amylase output stimulated by intravenous infusion of CCK-8 in a dose of 0.06 micrograms/kg/h. The ID50 (half-maximal inhibition dose) of KSG-504 for CCK-8-stimulated amylase secretion was 3.4 mg/kg/h. Moreover, intraduodenal KSG-504 (5 and 25 mg/kg/h) dose dependently suppressed pancreatic juice volume, and amylase output increased with intraduodenal infusion of casein (400 mg/h). It is concluded that KSG-504 administered intraduodenally has a significant, potent inhibitory action on the exocrine pancreas stimulated by exogenous CCK and intraduodenal casein.

The effect of a thromboxane A2 receptor antagonist (ONO 3708) on ischemia-reperfusion injury of the dog pancreas.

The effects of a thromboxane A2 receptor antagonist, ONO 3708, on ischemia-reperfusion injury of the pancreas were evaluated using an isolated in-vivo-perfused dog pancreas model. Pancreatic endocrine and exocrine function were stimulated with cholecystokinin octapeptide (10(-12) mol). This dose significantly increased endogenous prostaglandin I2 and thromboxane A2 production by the pancreas (both P < 0.001). A period of 60 min of ischemia and subsequent reperfusion induced an increase of pancreatic amylase release (P < 0.01) and a decrease of insulin release (P < 0.01). There was also a decrease of pancreatic juice and pancreatic bicarbonate and amylase output (au P < 0.01), suggesting damage to the acinar, ductular, and beta cells. Intravenous administration of ONO 3708 (200 micrograms/kg/min) throughout the experiment prevented these abnormalities of pancreatic secretion. It also reduced the plasma lipid peroxide level in the venous drainage (P < 0.01) and elevated the prostaglandin I2 level (P < 0.01) without changing thromboxane A2 levels. ONO 3708 thus appeared to protect the pancreas from ischemia-reperfusion injury by reducing the peroxidation of cell membrane lipids and by decreasing the thromboxane A2/prostaglandin I2 ratio, which is a predictor of cellular injury.

Canine model of chronic pancreatitis due to chronic ischemia.

An experimental model of chronic pancreatitis was produced by a chronic ischemia which was induced by ligation and separation of branches flowing into the left pancreatic lobe from the splenic artery. Macroscopic findings at 3 and 6 months after model preparation showed that the pancreas was hard, with severe inflammatory change. In the secretin-cerulein test at 3 and 6 months, the flow rate of pancreatic juice, amylase output and bicarbonate concentration were significantly reduced as compared with the controls. The histopathological findings consisted of a decrease in the pancreatic parenchyma, replacement of fat, severe inflammatory cell infiltration, extensive fibrosis and tubular complexes. As this model closely resembles human chronic pancreatitis, we conclude that ischemia is an etiological factor in chronic pancreatitis.

Suppressive role of the islet-acinar axis in the perfused rat pancreas

Background: The stimulating effects of insulin on the exocrine pancreas are well known. The effects of other islet hormones, however, are controversial. The aim of the present study was to determine whether the isletacinar axis, as a whole, is stimulatory or inhibitory. Because we have shown that retrograde perfusion reverses the islet-acinar directed microcirculation, retrograde perfusion was expected to remove the overall effects of islet hormones from the acinar tissue. Methods: Rat pancreata were perfused (7 mmol/L glucose plus 3 mmol/L mixed amino acids) either anterogradely or retrogradely. Pancreatic juice flow, protein output, and amylase output were measured. Results: When perfusion was switched from anterograde to retrograde, juice flow increased threefold without changes in protein and amylase output. When cerulein (10−10 mol/L) was infused, retrograde protein and amylase responses were larger than anterograde responses (each, n = 7; 2.71 ± 0.23 vs. 1.71 ± 0.11 mg/40 minutes; 173 ± 17 vs. 98 ± 8 U/40 minutes; mean ± SE; both, P < 0.01). Somatostatin-14 and rat pancreatic polypeptide (each, 10−9 mol/L) reduced the retrograde protein and amylase responses, but not juice flow, to the anterograde response levels. Conversely, these peptides did not affect exocrine function during anterograde perfusion. Conclusions: A suppressive role of the islet-acinar axis via endogenous somatostatin and/or pancreatic polypeptide is suggested.

Modulation of human periodic interdigestive gastrointestinal motor and pancreatic function by the ileum.

Following ingestion of a meal, unabsorbed nutrients may reach the distal intestine partly after the termination of the prandial period, i.e., in the presence of interdigestive motor and secretory patterns. To determine if interdigestive motility and pancreatic enzyme secretion are modulated by the delivery of nutrient into the ileal lumen, six fasting volunteers were intubated with an oroileal multilumen tube system that permitted multiple small intestinal manometry, gastric and duodenal aspiration, and perfusions of marker and test solutions. Ileal perfusions of nutrient or saline solutions were started during phase I of the interdigestive motility cycle. Ileal perfusion with carbohydrate or lipids increased the duration of motor quiescence and decreased the length of the interdigestive cycle, mainly by decreasing the proportion of phase II activity compared with ileal saline (p < 0.01). Pancreatic outputs of amylase, trypsin, and chymotrypsin prior to ileal perfusions were low because, due to the protocol, perfusions were started during phase I. With ileal saline, enzyme outputs increased (p < 0.05) in association with the occurrence of phase II motility, as expected. By contrast, ileal carbohydrate and triglyceride perfusion prevented the phase II-associated increase in enzyme outputs (p < 0.05). The data suggest that the presence of nutrients within the ileal lumen may modulate interdigestive motor and pancreatic functions.

Effect of Insulin Administration on Contents, Secretion, and Synthesis of Pancreatic Lipase and Colipase in Rats

After insulin administration in vivo, changes in pancreatic lipase, colipase and amylase contents and outputs were assayed and quantitatively compared. The incorporation of [35S]cysteine into individual enzymes was measured. The mRNA coding for lipase and amylase were determined by dot-blot hybridization. It was found that insulin dose-dependently decreased lipase and colipase contents, but only slightly decreased amylase content. Four hours after insulin administration (0.5 U/100 g), the contents of lipase and colipase decreased 80 and 72%, respectively, while amylase content decreased only about 25%. The decrease in amylase content was accompanied by a 21% increase in its output. The outputs of lipase and colipase only increased transiently and then sharply decreased to a level much lower than control. Total outputs of lipase and colipase could not quantitatively explain the great loss of lipase and colipase contents caused by insulin administration. After insulin injection, the incorporation of [35S]cysteine into amylase increased by 21%, whereas incorporation into lipase and colipase decreased by 18 and 25%, respectively. Dot-blot hybridization with cDNA probes revealed that lipase mRNA decreased by 50% 4 h after insulin administration, whereas mRNA for amylase did not significantly change. The results indicate an inhibitory effect of insulin administration on synthesis of pancreatic lipase and colipase, with the inhibition of lipase synthesis being at pretranslational level.

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.