In vivo action of bombesin on exocrine pancreatic secretion in the rat: independent of cholecystokinin and cholinergic mediation

This study evaluates the effect of bombesin on pancreatic enzyme secretion in the rat and determines whether the stimulatory action of bombesin is mediated through the release of cholecystokinin (CCK) or via a cholinergic pathway. We performed in vivo experiments on conscious rats prepared with cannulae inserted in the pancreatic duct, in the external jugular vein, and in the duodenum. Intravenous infusion of bombesin stimulated pancreatic protein output in a dose-dependent fashion. Bombesin infused at 5 micrograms/kg/h stimulated pancreatic protein secretion from a basal of 12 +/- 5 to 42 +/- 10 mg/h. Infusion of proglumide (400 mg/kg/h) did not affect the stimulatory effect of bombesin on pancreatic protein secretion (38 +/- 5 mg/h). In contrast, infusion of proglumide abolished the pancreatic protein output elicited by intravenous infusion of CCK8 (500 ng/kg/h). This suggests that bombesin does not act through CCK to mediate exocrine pancreatic secretion. In separate studies we intravenously infused rats with atropine (100 micrograms/kg/h) prior to infusion with bombesin. Administration of atropine slightly decreased secretory volume but did not affect the action of bombesin. Combined administration of atropine and proglumide also did not affect pancreatic protein output stimulated by bombesin. Since infusion of neither proglumide nor atropine inhibited the stimulatory action of bombesin, the action of bombesin in the rat is probably direct and not through the release of CCK or via a cholinergic pathway.     

Trypsin suppression of pancreatic enzyme secretion. Differential effect on cholecystokinin release and the enteropancreatic reflex

We have recently demonstrated that intraduodenal perfusion of trypsin inhibits phenylalanine-stimulated pancreatic enzyme secretion by suppression of release of cholecystokinin (CCK). It is not known whether trypsin in the duodenum inhibits pancreatic secretion stimulated by a cholinergic mechanism. To investigate this question gastrointestinal intubation and perfusion were performed in 12 healthy subjects. Volume and osmoreceptors in the duodenum, which are known to elicit pancreatic secretion through cholinergic pathways, were stimulated by infusing increasing volumes (1.0, 2.5, and 5.0 ml/min) of normal saline or increasing osmolality (300, 400, 500 mosmol) of NaCl solution. Increasing the rates of intraduodenal perfusion of normal saline or increasing the osmolality of the duodenal perfusates caused a dose-related increase in pancreatic trypsin and chymotrypsin outputs without affecting basal plasma CCK levels (0.9 +/- 0.1 pM). The volume- or osmolality-stimulated pancreatic secretions were abolished by atropine, but not by intraduodenal perfusion of trypsin. In contrast, intraduodenal perfusion of phenylalanine (10 mM) produced a significant increase in plasma CCK levels (6.7 +/- 0.8 pM) and a three- to fourfold increase in pancreatic enzyme outputs. Perfusion of the duodenum with bovine trypsin (1 g/L) reduced the plasma CCK levels to basal values and significantly attenuated the phenylalanine-stimulated enzyme secretion to 63% +/- 4% of control. Simultaneous administration of atropine and intraduodenal perfusion of trypsin completely abolished the pancreatic enzyme response to phenylalanine stimulation. These studies indicate that the intestinal phase of human pancreatic enzyme secretion is under both hormonal and neural control. Intraduodenal trypsin inhibits only pancreatic secretion mediated by CCK release, and not that mediated by cholinergic mechanisms. These observations suggest that feedback regulation of pancreatic enzyme secretion is stimulus specific.     

Interaction of the cholinergic system and cholecystokinin in the regulation of endogenous and exogenous stimulation of pancreatic secretion in humans.

Pancreatic enzyme secretion is regulated in humans by the cholinergic system and by cholecystokinin (CCK). The interaction between both regulatory systems in response to exogenous and endogenous stimulation was analyzed in the present study using the cholinergic antagonist atropine and the CCK antagonist loxiglumide. A dose-dependent stimulation of pancreatic enzyme output was achieved either by duodenal perfusion of graded caloric loads or by IV infusion of increasing doses of cerulein. Prestimulated pancreatic secretion was inhibited by atropine and loxiglumide. Atropine furthermore almost completely blocked meal-stimulated pancreatic secretion, whereas loxiglumide caused 60% inhibition. The enzyme response to graded doses of exogenous CCK was significantly inhibited by atropine and loxiglumide. Plasma levels of CCK were not altered by atropine but increased with infusion of loxiglumide. This study supports the concept that pancreatic enzyme secretion is predominantly dependent on a cholinergic tone and that CCK modulates the enzyme-secretory response.     

Effect of atropine on responses of exocrine pancreas and plasma cholecystokinin to intraduodenal amino acids in dogs

The effect of atropine on responses of exocrine pancreas and plasma cholecystokinin (CCK) to intraduodenal mixed amino acids has been studied in conscious dogs with Thomas gastric and duodenal fistulae. Intraduodenal amino acids provoked significant increase of pancreatic protein output and of plasma CCK concentration. Atropine significantly reduced protein output only in the initial peak after amino acid administration. Atropine had no significant effect on plasma CCK. It is indicated that cholinergic nerves predominate in the early pancreatic protein response to intraduodenal amino acids and CCK prevails in the later phase, though these two factors do not seem to be the only factors responsible for the secretion.     

Mechanism of release of endogenous cholecystokinin by jejunal amino acid perfusion in man

Ertan et al have shown that the perfusion of the proximal jejunum with a mixture of amino acids (MAA) in physiological concentration releases endogenous cholecystokinin (CCK) in man. In the present experiment, we investigate the mechanism by which jejunal MAA perfusion mediates an increase in exocrine pancreatic and biliary secretions. The effects of a bolus of topical anesthetic (oxethazaine, 0.5 mg/kg of 0.4% solution) or the simultaneous jejunal perfusion of a topical anticholinergic agent (atropine, 1 mg/liter) were studied in the same five normal patients on different days. Suppression of the response to jejunal MAA perfusion but not to intravenous infusion of CCK or jejunal saline perfusion, was noted in these normal subjects following jejunal application of oxethazaine and atropine. These results suggest a local involvement of the cholinergic mechanism for the endogenous release of CCK, while exogenous CCK acts directly on the pancreatic cells.This work was presented, in part, at the 72nd Annual Meeting of the American Gastroenterological Association, May 13, 1971 in Bal Harbour, Florida.This work was supported by Training Grant, TR 15A from the Veterans Administration Hospital.Dr. Ertan is a former instructor in Medicine, Gastroenterology Sections at the Hospital of the University of Pennsylvania and the Philadelphia Veterans Administration     

Effect of a liquid meal given as a bolus into the jejunum on human pancreatic secretion

Major features of pancreatic secretion stimulated by a meal depend on intestinal phase mechanisms. However, an intrajejunal (i.j.) meal infusion is widely used for the treatment of inflammatory pancreatic diseases when the resting of the gland is desired. This study was undertaken to compare the effects of an intragastric (i.g.) and an i.j. complete fluid (Lundh) test meal on pancreatic enzyme secretion. Eight men (mean age, 43 years; range, 31-48) free from pancreatic disease were studied. Pancreatic secretion was measured via a multiple-lumen tube by aspiration of the duodenal juice. After a fasting period, the Lundh test meal was placed in the stomach or the upper jejunum. After the i.g. administration of the test meal, the aspirated duodenal juice was reinfused into the jejunum. The effect of atropine infusion (0.5 microg/kg/h) on the pancreatic enzyme secretion was studied. The pancreatic amylase, trypsin, and lipase outputs were determined. The plasma levels of cholecystokinin (CCK) and of gastrin were measured by bioassay and radioimmunoassay, respectively. The trypsin, amylase, and lipase secretions increased significantly after either an i.g. or an i.j. test meal intake. The trypsin, amylase, and lipase outputs were significantly decreased during the i.j. perfusion as compared with i.g. administration. The gastrin levels increased significantly after i.g., but remained unchanged after i.j. administration. The CCK release attained its maximum 40 and 60 min after the i.g. and i.j. test meal, respectively. However, the CCK release was significantly lower during the i.j. administration as compared with i.g. perfusion. An atropine infusion significantly reduced the i.g. and i.j. test meal-stimulated enzyme outputs. An i.j.-administered meal stimulates the pancreatic enzyme secretion, but this effect is significantly lower than that which occurs on i.g. administration. The i.j. meal-stimulated secretion of pancreatic enzymes is subject to both cholinergic and peptidergic regulation. The deficiency of gastrin and the delayed and decreased CCK release are believed to account for the reduced enzyme output.     

Differential effects of atropine and a cholecystokinin receptor antagonist on pancreatic secretion

The present study evaluates the effect of atropine and of the cholecystokinin receptor antagonist loxiglumide on feedback regulation of basal pancreatic secretion in 6 healthy volunteers. The intraduodenal instillation of the protease inhibitor camostate reduced enzymatic activities of trypsin and chymotrypsin by 80%. This was accompanied by a strong increase in amylase and lipase output. The intravenous infusion of atropine (5 micrograms/kg.h) completely abolished the stimulatory effect of camostate on enzyme output. The infusion of loxiglumide (10 mg/kg.h) caused no changes in camostate-induced stimulation of enzyme output. Plasma levels of cholecystokinin were not altered after intraduodenal instillation of camostate whether atropine, loxiglumide, or saline were infused. We suggest that the protease inhibitor camostate, by inhibition of the enzymatic activity of trypsin and chymotrypsin, interferes with feedback regulation of basal pancreatic secretion in humans, and this mechanism is predominantly mediated by the cholinergic system.     

Atropine enhances food-stimulated CCK secretion in the rat

The effect of atropine on plasma cholecystokinin (CCK) and pancreatic secretion during intraintestinal infusion of a conventional defined formula liquid diet (Ensure HN, Ross Laboratories, 1.06 kcal/ml) was studied in conscious rats. Rats were prepared with cannulae draining bile and pancreatic juice, which were returned to the duodenum at all times. Pancreatic secretion was monitored during intraduodenal infusion of 0.15 M NaCl for 2 h followed by Ensure HN, both infused at 4.62 ml/h. Rats were infused i.p. with atropine (500 micrograms/kg/h) or vehicle throughout the experiment, beginning 1 h before monitoring of basal pancreatic secretion. Basal and 15 min postprandial plasma CCK concentrations were determined by bioassay. Atropine inhibited basal pancreatic protein secretion by approximately 60%. However, protein secretion during infusion of the diet was not decreased by atropine, due to a larger incremental pancreatic protein secretory response in atropine-treated rats. Plasma CCK 15 min after beginning the diet infusion was significantly increased by atropine (8.09 +/- 1.77 pM in atropine-treated rats versus 3.14 +/- 0.64 pM in controls). The results indicate that rats compensate for loss of cholinergic input to the pancreas by increasing CCK release in response to a meal. This is hypothesized to occur by virtue of reduced feedback inhibition of CCK release due to anticholinergic reduction of basal levels of intestinal protease activity.     

Release of cholecystokinin and exocrine pancreatic secretion in response to an elemental diet in human subjects

We investigated in human volunteers the effects of an elemental diet (ED) containing amino acids on release of endogenous cholecystokinin (CCK) using a highly sensitive and specific radioimmunoassay of CCK and exocrine pancreatic secretion using a dye dilution technique with polyethylene glycol 4000 as a nonabsorbable marker. Intrajejunal administration of ED at three different infusion rates (12.5, 25, and 50 ml/30 min) resulted in a significant increase in plasma CCK concentration in a dose-related manner. Plasma concentrations of gastrin or secretin, however, did not change. Pancreatic secretion of protein, amylase, and bicarbonate also increased significantly. The change in pancreatic secretion of protein, amylase, and bicarbonate output paralleled that of the circulating CCK level but not that of plasma secretin. Thus, the dose of amino acid contained in ED recommended for clinical use can significantly stimulate the release of CCK from the upper small intestine, raising the plasma concentration of CCK. This level can evoke a significant increase in exocrine pancreatic secretion.This work was supported by United States Public Health Grant NIH AMDDK 25962.     

Duodenal volume and osmoreceptors in the stimulation of human pancreatic secretion

It is generally accepted that the intestinal phase of pancreatic secretion is initiated by the stimulation of chemoreceptors sensitive to fat and protein degradation products and hydrogen ions. The effect of the volume and osmolality of food emptied by the stomach into the duodenum has received less attention. We investigated the effects of these factors on the stimulation of pancreatic secretion by studying 8 healthy male volunteers (ages 23-69 yr), in random order on 3 separate days. On day 1, an amino acid mixture (L-phenylalanine, L-tryptophan) was infused intraduodenally at increasing rates, 0.2, 0.8, and 3.2 ml X min-1. On day 2, normal saline was infused into the intestine at the same increasing rates. On day 3, mannitol solutions of increasing osmolality 370, 520, and 700 mosmol X kg-1 were infused into the duodenum at 0.2 ml X min-1. Duodenal contents were continuously aspirated via a double-lumen tube and PEG 4000 was used as a recovery marker. All studies were repeated 90 min later during i.v. infusion of atropine (20 micrograms X kg-1 X h-1). Increasing volumes of amino acids significantly increase amylase and bicarbonate output (p less than 0.05) in a stepwise fashion. Increasing volumes of saline also caused a similar stepwise increase in amylase and bicarbonate output. Furthermore, increasing osmolality caused an increase in enzyme output up to 520 mosmol X kg-1 and no increase was seen thereafter. The responses seen with volume and osmolality were approximately 40% of that obtained with the amino acids. All responses were significantly reduced (p less than 0.05) during atropine infusion. We conclude that the human duodenum contains receptors for volume and osmolality that stimulate both pancreatic enzyme and bicarbonate secretion. Both mechanisms are atropine sensitive, suggesting they are mainly neurally mediated.     

Effect of atropine on pancreatic secretion in conscious rats

The effect of atropine on exocrine pancreatic secretion was investigated in conscious rats. Intravenous atropine infusion decreased nonstimulated protein secretion during recirculation of pancreatic juice into the duodenum D50 = 15-20 micrograms/kg/h. The maximum inhibition from protein secretion (-89%) was obtained with 600 micrograms/kg/h. With larger doses, the inhibition was less. The response to secretin and cholecystokinin-pancreozymin was not significantly modified by atropine. When pancreatic juice was diverted during the course of an intravenous atropine infusion, the first 1-hour peak of protein output was significantly decreased, but the following 2-hour period was increased, the sum of these 2 periods being similar in both conditions. The response to soybean trypsin inhibitor during recirculation was decreased as well as the first peak after diversion. During atropine infusion fluid secretion decreased more powerfully after 1 h diversion and after soybean trypsin inhibitor than during recirculation of pancreatic juice. It is suggested that during recirculation of pancreatic juice nonstimulated protein secretion is mostly (89%), and water secretion is partially controlled by cholinergic mechanisms. After soybean trypsin inhibitor stimulus and during the early phase following juice diversion protein secretion seems to be partly under the control of cholinergic mechanisms. However, during the latter phase following diversion, it is not so. Parasympathetic stimulation appears also to play a significant, although less important, role in fluid secretion.     

Role of cholecystokinin in the regulation of the interdigestive phase of pancreatic secretion

The rate of pancreatic secretion during the interdigestive state varies with the phase of interdigestive motility. During phases II and III of interdigestive motility, pancreatic secretion is greatest, and minimal during phases I and IV. Pancreatic polypeptide and motilin have been reported to be increased during phases II and III but do not appear to be responsible for the stimulation of pancreatic secretion. We have investigated the role of cholecystokinin (CCK) in regulating pancreatic secretion during the interdigestive state. Eight volunteers underwent a study of interdigestive duodenal motility with a catheter that collected pancreatic secretions at the ligament of Treitz. The phase of motility was correlated with the output of trypsin and the plasma CCK levels. The output of trypsin during phases II and III was 0.9 +/- 0.2 and 1.0 +/- 0.2 mg/kg/h, respectively, and decreased to 0.3 +/- 0.1 mg/kg/h during phase IV-I (p less than 0.05). To determine if the output of trypsin during phases II and III was responsible for the increases in plasma CCK, the effect of intraduodenal trypsin, 3 mg/kg/h, in five volunteers was determined. The infusion significantly increased the output of trypsin to a mean of 3.1 +/- 1.9 mg/kg/h (p less than 0.05). The plasma CCK concentration increased with intraduodenal trypsin from 20.4 +/- 5 to 26.4 +/- 3.7 pg/ml (p less than 0.05). The infusion study was repeated in two volunteers with heat-inactivated trypsin. The mean CCK level rose from 19.6 +/- 4 to 23.8 pg/ml.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dose-response effects of atropine on pancreatic secretory response to intravenous cerulein in dogs

In conscious dogs with gastric and pancreatic fistulas, we studied the effect of i.v. atropine in doses ranging from 1.8 to 29 nmol/kg/h on the pancreatic secretory response to i.v. cerulein in doses ranging from 3.7 to 118 pmol/kg/h. Cerulein was given with an i.v. background infusion of secretin (20.5 pmol/kg/h), started 1 h before the lowest dose of cerulein was given. Secretin alone did not stimulate pancreatic protein output above basal. Doses of 7 and 29 nmol/kg/h of atropine significantly (p less than 0.05) decreased the protein output during secretin. A dose of 29 nmol/kg/h, but not lower doses, of atropine significantly inhibited the bicarbonate response to secretin. A dose of 3.7 pmol/kg/h and all higher doses of cerulein significantly stimulated bicarbonate and protein output above the value observed during secretin alone. None of the three doses of atropine given had any significant effect on the incremental bicarbonate and protein responses to cerulein. Secretin and cerulein did not alter basal heart rate; only the highest dose (29 nmol/kg/h) of atropine significantly increased heart rate. These findings are compatible with the hypothesis that cholinergic nerves do not alter the effect of exogenous cerulein, a CCK analogue, on pancreatic bicarbonate and protein secretion in dogs.     

Intraduodenal cholecystokinin octapeptide (CCK-8) can stimulate pancreatic secretion in the calf

Summary The effect of CCK-8 administered into the duodenal lumen and into the systemic blood on pancreatic, secretion and duodenal migrating myoelectric complex (MMC) was studied in four calves. Simultaneous MMC recordings and collections of pancreatic juice were performed on valves that had been fasted overnight. Intraduodenal (o, 100, and 300 pmol/kg body wt) and intravenous (0, 30, and 100/pmol kg) infusions of CCK-8 were made for 5 min during the no spiking activity (NSA) phase of duodenal MMC associated with a nadir of periodic pancreatic secretion. CCK-8 was also administered during continuous atropine infusion (5 μg/kg/min). Both intraduodenal and intravenous infusions of CCK-8 resulted in marked pancreatic responses in juice outflow, bicarbonate output, and protein output. Atropine decreased pancreatic response (protein output) to intravenous CCK-8 and markedly inhibited the response (juice flow, bicarbonate, and protein output) to intraduodenal CCK-8. Infusions of CCK-8 did not affect the duration of MMC in the duodenum. Plasma CCK increased significantly after intravenous infusion, but remained unchanged after intraduodenal infusion. In conclusion, CCK-8 can stimulate pancreatic secretion from the duodenal lumen, possibly via a cholinergic mechanism in the calf.     

The role of gastrointestinal peptides on pancreatic secretion in response to different stimulants in conscious rats

Summary Effects of intragastric food, intraduodenal amino acids, and intravenously administered bombesin and gastrin-releasing peptide (GRP) were examined in conscious rats with pancreatic fistula in terms of responses of exocrine pancreatic secretion, plasma levels gastrin, and cholecystokinin (CCK). Pancreatic juice and blood samples were collected at regular intervals before and after the stimuli. Intragastric food increased pancreatic secretion and plasma levels of gastrin and CCK. Intraduodenal infusion of amino acids had no effect on pancreatic secretion and plasma levels of gastrin and CCK. Intravenous infusion of bombesin at 1 μg/kg/h induced significant increases in pancreatic volume and protein outputs, but had no effect on plasma levels of gastrin and CCK. Bombesin infusion at 10 μg/kg/h resulted in significant increases in pancreatic volume and protein outputs as well as plasma gastrin levels, but had no effect on plasma CCK levels. Intravenous infusion of GRP induced increases in pancreatic volume and protein outputs and plasma gastrin levels, but had no effect on CCK levels. Antrectomy resulted in significant decreases in basal levels of plasma gastrin. GRP-stimulated pancreatic volume and protein outputs were not significantly changed by antrectomy. In rats that underwent antrectomy, GRP infusion significantly increased pancreatic volume and protein outputs, but had no effect on plasma levels of gastrin and CCK. Food-stimulated pancreatic secretion and plasma levels of gastrointestinal peptides of rats were similar to other species, but amino acids, bombesin, or GRP may not be the stimulants for CCK release in rats. The stimuli that release CCK from duodenal mucosa probably varies among species.     

Effect of atropine on intestinal phase of pancreatic secretion in man

The effect of atropine on prestimulatory and Lundh-meal-stimulated pancreatic secretion and on plasma cholecystokinin (CCK) levels has been studied in 20 human volunteers. Prestimulatory secretion was lowered by infusion of atropine. From 10 to 30 min after ingestion of the Lundh meal, atropine had no effect on secretion. From 30 to 120 min, the stimulated enzyme secretion was reduced by 90% during infusion of atropine. Plasma CCK levels were not altered by atropine. Similar results were obtained when the test meal was instilled into the duodenum to exclude a delay of gastric emptying caused by atropine. These data show that cholinergic blockade does not interfere with CCK-mediated stimulation of pancreatic secretion during the first 30 min after ingestion of a meal, and that afterwards the intestinal phase is mainly under cholinergic control.     

Effect of parenteral amino acids on human pancreatic exocrine secretion

Parenteral administration of amino acids has been utilized for the nutritional support of patients with a variety of gastrointestinal disorders including protracted pancreatitis and pancreatic fistulae. However, the effect of parenteral amino acid administration alone on human pancreatic secretion has not been studied. We have studied the short-term effect of parenteral administration of amino acids on pancreatic exocrine secretion in seven healthy men. A double-lumen tube was placed in the duodenum and polyethylene glycol was perfused into the proximal duodenum at the rate of 10 ml/min. A second double-lumen tube was placed in the stomach and bromsulfthalein was perfused into the cardia. Samples of duodenal contents were aspirated and gastric contents recovered during one hour of intravenous saline infusion followed by two hours of an amino acid mixture infusion. Hourly outputs of protein and pancreatic enzymes were determined, correcting for duodenogastric reflux based on concentrations of both markers in the samples. Despite an average increase of 72% in the plasma concentration of the infused amino acids, the outputs of protein, trypsin and amylase did not change significantly during amino acid infusion; the output of lipase decreased significantly during amino acid infusion. Two subjects were given intravenous secretin and cholecystokinin following amino acids; this resulted in increased outputs of protein, trypsin, and amylase in both. We conclude that the parenteral administration of amino acids to healthy young men does not stimulate pancreatic enzyme secretion as measured by the method using duodenal marker perfusion at the rate of 10 ml/min.This research was supported by a grant from U.S. Veterans Administration.     

Effect of insulin and glucose on basal and cholecystokinin-stimulated exocrine pancreatic secretion in humans

Pancreaticobiliary secretion is reduced during acute hyperglycemia. In nondiabetics, this inhibitory effect also may result from hyperinsulinemia. Therefore we investigated the effects of acute hyperglycemia and euglycemic hyperinsulinemia on basal and cholecystokinin (CCK)-stimulated pancreaticobiliary secretion. Nine healthy volunteers (age, 22-52 years) were studied on three occasions in random order during (a) intravenous saline (control), (b) hyperglycemic hyperinsulinemic clamping (HG; plasma glucose at 15 mM), and (c) euglycemic hyperinsulinemic clamping (HI; plasma insulin at 150 mU/L, glucose at 4-5 mM). Duodenal outputs of bilirubin, amylase, trypsin, and bicarbonate were measured under basal conditions and during CCK infusion (0.25 and 0.5 IDU/kg/h). Basal pancreaticobiliary secretion was significantly (p < 0.05) reduced during both HG and HI. During low-dose CCK stimulation, HG significantly (p < 0.05) reduced bilirubin and trypsin output compared with control. In contrast, HI did not significantly reduce pancreatic enzyme and bilirubin output during low-dose CCK infusion. During high-dose CCK infusion, neither HI nor HG influenced pancreatic enzyme and bilirubin output. Pancreatic bicarbonate output was not influenced by CCK and remained significantly (p < 0.05) reduced during HI and HG compared with control. It is concluded that during both acute hyperglycemia and euglycemic hyperinsulinemia, basal pancreaticobiliary secretion is significantly reduced. CCK-stimulated pancreatic enzyme and bilirubin output is significantly reduced only during hyperglycemia. The inhibitory effect of hyperglycemia on pancreaticobiliary secretion in healthy volunteers may occur independent of insulin.     

Effect of atropine on feedback regulation of pancreatic enzyme secretion in rats

The effect of atropine on the feedback regulatory mechanism of pancreatic enzyme secretion exerted by intraluminal trypsin was investigated in conscious rats. Intravenous atropine infusion (50 micrograms/kg/h) suppressed pancreatic enzyme secretion to the same extent in both the presence and the absence of pancreatic juice in the intestine. However, with or without atropine infusion, pancreatic secretory rate was higher throughout diversion of pancreatic juice than during intraduodenal return of the juice. Atropine also inhibited the stimulatory response to intraduodenal trypsin inhibitor and intravenous caerulein. The atropine-induced inhibitory effect was not significantly different between the two experimental conditions. Regardless of atropine administration, both trypsin inhibitor and caerulein caused a significant increase in pancreatic secretion. The results suggest that cholinergic mechanisms have little influence on the feedback regulation. Cholinergic mechanisms may play an important role in maintaining the physiologically basal secretion because the basal secretion is atropine-sensitive.     

Neurotensin and the exocrine pancreas

It has been postulated that neurotensin (NT) has a physiological role in the regulation of the exocrine pancreas, but this is controversial. Using the Thomas cannula canine model, the effect of intravenous NT, in physiological and pharmacological doses on exocrine pancreatic secretion, and on plasma pancreatic polypeptide, secretin and cholecystokinin (CCK) levels is reported. The infusion of physiological doses of NT alone (0.2 pmol/kg per min) did not stimulate pancreatic secretion; however, in conjunction with secretin, NT stimulated protein and bicarbonate output, the latter synergistically. Higher doses of NT (20 and 100 pmol/kg per min) resulted in a dose-dependent stimulation of pancreatic volume, bicarbonate and protein secretion. Cholinergic blockade with atropine reduced pancreatic secretion stimulated by low doses of NT (2–20 pmol/kg per min), but at higher doses (100 pmol/kg per min) protein secretion was reduced whilst bicarbonate secretion was enhanced. The infusion of graded doses of NT had no effect on plasma secretin or CCK levels. In contrast, NT did release pancreatic polypeptide in a dose-dependent manner, but only at pharmacological infusion levels. NT, acting synergistically with other hormones, may thus play a role in exocrine pancreatic stimulation.