Infusion Of Secretin Research Articles

Duodenal mucosal bicarbonate secretion in pigs is accompanied by compensatory changes in pancreatic and biliary HCO3- secretion.

The purpose of the study was to examine the effect of stimulation and inhibition of duodenal mucosal bicarbonate secretion on pancreatic and hepatic bicarbonate secretion in response to acid. The effect of inhibition (indomethacin) or stimulation (misoprostol) of duodenal mucosal bicarbonate secretion on pancreatic and biliary bicarbonate secretion in response to intraduodenal infusion of HCl or intravenous infusion of secretin was studied in anaesthetized pigs. The hepatic and pancreatic response to exogenous secretin was not significantly altered by stimulation/inhibition of duodenal bicarbonate secretion. However, pancreatic and biliary bicarbonate secretion in response to duodenal acidification was significantly augmented by inhibition of duodenal mucosal bicarbonate secretion; conversely, it was reduced by stimulation of duodenal bicarbonate secretion. The increase in plasma secretin levels in response to duodenal acidification was reduced by stimulation and augmented by inhibition of duodenal mucosal bicarbonate secretion. Duodenal mucosal bicarbonate secretion can serve as a modulator of both pancreatic and biliary bicarbonate secretion in response to luminal acidification, possibly through regulation of the release of secretin.

Inhibition of pancreatic secretion under long-term octreotide treatment in humans.

The somatostatin analogue octreotide (SMS 201-995) is a potent inhibitor of human exocrine pancreatic secretion. In the present study we analyzed the effect of octreotide (3 x 100 micrograms, daily) given over a time period of 7 days on hormone-stimulated exocrine pancreatic secretion in 6 healthy volunteers using a secretin-ceruletide test. The secretin-ceruletide test was carried out before, following the first injection of octreotide (day 1) and after a 7-day treatment with 3 x 100 micrograms octreotide daily. Duodenal fluid was collected over 30 min without stimulation, over 60 min following a bolus injection of 1 U/kg body weight secretin, and over 60 min during a continuous infusion of secretin and ceruletide. Following the first injection of octreotide and following 7 days of octreotide treatment secretin/ceruletide-stimulated amylase secretion was significantly reduced. Trypsin and chymotrypsin secretion was significantly reduced after the first injection of octreotide when pancreatic secretion was stimulated by secretin and ceruletide simultaneously. However, secretin and ceruletide-induced trypsin and chymotrypsin secretion was not inhibited after 7 days of octreotide treatment. Baseline, secretin and secretin/ceruletide-stimulated bicarbonate output were not influenced by octreotide either following the first injection of octreotide or the 7 days' treatment. Octreotide is a potent inhibitor of secretin/ceruletide-stimulated pancreatic amylase, trypsin and chymotrypsin secretion. However, following a 7-day treatment with octreotide this inhibition is only persistent for pancreatic amylase secretion.

The effect of intravenous cadmium on exocrine and endocrine pancreatic functions in conscious dogs.

This study was conducted in conscious dogs to investigate the effect of cadmium on exocrine pancreatic secretion and plasma levels of pancreatic polypeptide (PP). Mongrel dogs weighing 20-25 kg were prepared with chronic gastric and pancreatic fistulas, and were acclimated for 3 wk prior to studies. The dogs were given iv infusion of saline, secretin at 25 U/kg/h, cadmium at 0.15 mg/kg/h, or various combinations of these compounds. During the infusion, pancreatic juice and blood samples were collected at regular intervals. Secretin infusion stimulated pancreatic secretions. Infusion of cadmium alone had no effect on pancreatic secretions and plasma levels of PP. When cadmium infusion was stopped with the background infusion of secretin, pancreatic secretions and plasma levels of PP were significantly increased. This latent effect of cadmium on pancreatic secretions and plasma levels of PP was abolished by an iv injection of 100 mg/kg atropine. These results indicate that cholinergic signaling may be involved in the effect of cadmium on pancreatic exocrine secretions and PP release. The current study suggests that cadmium may have diverse physiological functions in both exocrine and endocrine pancreatic cells.

Exocrine pancreatic secretion in man following one week of M1‐muscarinic receptor blockade

A double-blind, randomized, placebo-controlled crossover study was performed to assess the influence of one week of selective M1-muscarinic receptor blockade on pancreatic exocrine secretion in man. Ten healthy subjects received telenzepine (3 mg p.o.) and placebo each for 8 days, with a 6-day drug-free washout interval between treatment sequences. On Day 8 of each sequence, pancreatic secretion was stimulated for 2 h by infusion of submaximal secretin (0.2 U.kg/h) followed by maximal stimulation with secretin (1.0 U.kg/h) and ceruletide (120 ng.kg/h). Telenzepine had no significant effect on secretory parameters during submaximal stimulation with secretin. During maximal stimulation, total protein, secretory volume, and output of amylase, trypsin and bicarbonate were unexpectedly increased by telenzepine. These findings might be partially explained by removal of the inhibitory influence of pancreatic polypeptide, which was depressed by telenzepine. Acute studies have shown that M1-receptor antagonists inhibit exocrine secretion. Our results suggest that adaptation of physiological mechanisms governing the exocrine pancreas may occur after one week of receptor blockade by a therapeutic dosage of telenzepine, to the extent that M1-blockade no longer inhibits secretion.

Inhibitory effect of intraduodenal administration of somatostatin analogue SDZ CO 611 on rat pancreatic exocrine secretion.

The inhibitory effect of the intraduodenal administration of a new somatostatin analogue, SDZ CO 611 (SDZ), on pancreatic secretion was evaluated in the rat. The exocrine pancreas was stimulated by either intravenous infusion of both secretion (0.06 CU/kg/h) and cholecystokinin octapeptide (CCK-8) (0.03 microgram/kg/h) or intraduodenal infusion of oleic acid (0.25 mmol/h) or casein (200 mg/h). Intraduodenal administration of SDZ in three different doses, 0.5, 1.0, and 2.0 mg/kg/h, resulted in dose-related inhibition of pancreatic secretion, including juice volume, bicarbonate, and amylase, stimulated by exogenous secretin and CCK. Intraduodenal oleic acid- and casein-induced increases in pancreatic secretion in terms of juice volume, bicarbonate, and amylase were also significantly suppressed by intraduodenal administration of SDZ in a dose of 2.0 mg/kg/h. Moreover, SDZ (2.0 mg/kg/h) significantly inhibited basal pancreatic secretion. It is concluded that the intraduodenal administration of SDZ inhibits pancreatic secretion stimulated by exogenous secretin and CCK-8 in physiological doses and by intestinal nutrients in the rat.

Peptide YY Inhibits Pancreatic Secretion via Cholinergic Pathways

The influence of extrapancreatic nerves and intrapancreatic cholinergic activity on the inhibition of pancreatic exocrine secretion by peptide YY (PYY) was studied in conscious dogs. Chronic pancreatic fistulae were created in five mongrel dogs while a second group of five dogs also underwent complete pancreatic denervation. After recovery, a continuous infusion of secretin (62 ng/kg/hr) and cholecystokinin (50 ng/kg/hr) was administered over 2 hr. An infusion of PYY (400 pm/kg/hr) was then given randomly, during either the first or second experimental hour. The experiments were then replicated with a continuous background infusion of (90 μg/kg/hr) bethanechol, a cholinergic agonist. The secretin/cholecystokinin-induced bicarbonate and protein outputs were significantly inhibited by PYY in both the innervated and denervated animals. In the denervated animals, bethanechol eliminated the inhibitory effects of PYY. We conclude that extrapancreatic nerves do not mediate the inhibitory effects of PYY. The results suggest that PYY inhibits secretin/ cholecystokinin-induced pancreatic response by an intrapancreatic cholinergic mechanism.

Role of endogenous nitric oxide in the control of canine pancreatic secretion and blood flow

Background: Endogenous nitric oxide has been implicated in the control of mesenteric circulation, but its role in the control of pancreatic blood flow and exorcine pancreatic secretion has not been studied. Methods: Secretory studies were performed on conscious dogs with chronic pancreatic fistulas, and changes in pancreatic blood flow were measured by laser Doppler flowmetry in anesthetized animals. Results: Infusion of NG-nitro-l-arginine did not affect basal pancreatic protein secretion but suppressed an increase of this secretion induced by l-arginine but not that induced by glyceryl trinitrate. Sham-feeding, meal feeding, and infusion of secretin plus cholecystokinin induced pancreatic protein outputs reaching, respectively, 30%, 74%, and 50% of cerulein maximum in these dogs. Infusion of NG-nitro-l-arginine caused a profound inhibition of these secretions, whereas the addition of l-arginine reversed this inhibition in part. NG-nitro-l-arginine or l-arginine added to the incubation medium of isolated canine pancreatic acini did not affect basal or cholecystokinin-induced amylase release. In anesthetized dogs, infusion of NG-nitro-l-arginine caused a significant reduction in the pancreatic blood flow both while resting and following stimulation with secretin plus cholecystokinin but did not affect this flow in animals treated with glyceryl trinitrate. Addition of l-arginine attenuated the decrease in pancreatic blood flow and the increase in systemic blood pressure caused by NG-l-nitro-arginine. Conclusions: Endogenous NO affects pancreatic secretion probably through the changes in the vascular bed.

Secretin and portal blood flow.

Using a duplex Doppler technique, we investigated the effect of low doses of secretin on the portal blood flow. In eight healthy volunteers successive intravenous secretin infusions of 0, 8, and 32 pmol x kg-1 x h-1 resulted in proportional increases in plasma secretin levels. The portal venous flow, however, was unaffected. A bolus injection of 930 pmol of secretin caused plasma secretin levels to increase 100-fold, whereas blood flow in the portal vein increased only by a factor three. This suggests that secretin in the present dose range is of no quantitative importance as a regulator of portal venous flow under physiologic conditions.

Effects of intraluminal peptide YY on pancreatic function.

Peptide YY (PYY) is released postprandially into both the circulation and the distal intestinal lumen. While circulating PYY inhibits pancreatic secretion and insulin release, the effects of intraluminal PYY on pancreatic function are unknown. The aim of the present study was to evaluate the effect of exogenous, intraileal luminal PYY on pancreatic exocrine function and fasting glucose levels. Chronic pancreatic and ileal fistulae (50 cm from the ileocecal valve) were created in nine mongrel dogs. The animals were given intravenous infusions of secretin (125 ng/kg/h) and cholecystokinin octapeptide (CCK-8, 50 ng/kg/h) for four hours. At the beginning of the second hour, either normal saline or PYY, at low [physiologic (2 ng/min)] or high [supraphysiologic (50 ng/min)] levels, was infused antegrade into the ileal fistula for two hours. Pancreatic juice was collected for PYY and glucose levels. Ileal luminal PYY infusions had no effect on pancreatic bicarbonate or protein output. Fasting serum PYY and glucose concentrations were unaffected by either dose of intraluminal PYY. We conclude that ileal luminal PYY does not influence pancreatic exocrine function or fasting glucose levels.

Philosophy of pharmacokinetic modelling

Ex vivo hemoperfused pancreaticoduodenal preparations from dogs have been used to study intraluminal and circulatory patterns of release of immunoreactive gastrin under basal conditions and after secretin stimulation. Bidirectional release of immunoreactive gastrin was maximal at 3 U/min secretin infusion, and release into pancreatic and duodenal juice exceeded that into portal venous blood. Molecular sieving chromatography of peptides with gastrin-like immunoreactivity recovered from duodenal and pancreatic juice indicated a single species of a molecular size equivalent to CCK8 and smaller than minigastrin (G-14). The exact identity has not been defined. This study demonstrates that secretin stimulates release of gastrin-like peptides into blood and lumen of extra-antral gastrin-producing tissues in the dog. Unidirectional gastrin release patterns from gastrinoma tissue may explain the paradoxical increase in plasma gastrin levels in response to secretin in patients with gastrinomas (Zollinger-Ellison syndrome).

Precorneal pharmacokinetics

Ex vivo hemoperfused pancreaticoduodenal preparations from dogs have been used to study intraluminal and circulatory patterns of release of immunoreactive gastrin under basal conditions and after secretin stimulation. Bidirectional release of immunoreactive gastrin was maximal at 3 U/min secretin infusion, and release into pancreatic and duodenal juice exceeded that into portal venous blood. Molecular sieving chromatography of peptides with gastrin-like immunoreactivity recovered from duodenal and pancreatic juice indicated a single species of a molecular size equivalent to CCK8 and smaller than minigastrin (G-14). The exact identity has not been defined. This study demonstrates that secretin stimulates release of gastrin-like peptides into blood and lumen of extra-antral gastrin-producing tissues in the dog. Unidirectional gastrin release patterns from gastrinoma tissue may explain the paradoxical increase in plasma gastrin levels in response to secretin in patients with gastrinomas (Zollinger-Ellison syndrome).

Effects of secretin on bile production in two kinds of cholestatic models by choledocho-caval fistula and bile duct ligation in rats.

Secretin is known to stimulate bile flow from the bile duct epithelium. To investigate the effects of secretin in cholestasis, we studied the response of the bile flow and the excretion of biliary components to secretin using two cholestatic models with or without damage to the bile duct epithelium. The model without bile duct epithelial damage was a choledocho-caval (CC) fistula over a 24-hour period, and the model with bile duct damage was a bile duct ligation over a 48-hour period. Secretin was administered by intravenous infusion for 30 minutes and bile was collected for 120 minutes. Controls were given saline similarly. The bile flow and biliary bicarbonate excretion rate were significantly increased after secretin infusion in the CC fistula rats when compared with the control rats, but no stimulation by secretin was observed in the ligated rats. These data indicate that secretin-induced bile production was enhanced under cholestatic conditions with no bile duct epithelial disturbance.

Role of endogenous secretin and cholecystokinin in intraduodenal oleic acid-induced inhibition of gastric acid secretion in rats

We investigated a possible role of endogenous secretin and cholecystokinin (CCK) in inhibition of gastric acid secretion induced by intraduodenal administration of oleic acid in rats. Intraduodenal administration of oleic acid emulsion in a dose of 1 mmol/hr resulted in significant inhibition of gastric acid secretion stimulated by intravenous infusion of pentagastrin (0.3 micrograms/kg/hr), and this was accompanied by an increase in the plasma concentration of both secretin and CCK, from 1.2 +/- 0.08 pM and 20.6 +/- 1.2 pM to 4.3 +/- 0.18 pM and 31.6 +/- 0.9 pM, respectively (P less than 0.001). Intravenous infusion of secretin (0.05 CU/kg/hr) inhibited pentagastrin-stimulated gastric acid secretion, but CCK-8 (0.03 micrograms/kg/hr) failed, although intravenous infusion of secretin and CCK in those doses produced plasma levels comparable to the levels achieved in response to oleic acid administration. Furthermore, the oleic acid-induced suppression of gastric acid secretion was blocked significantly by intravenous injection of rabbit anti-secretin serum (0.1 ml), but not by intravenous infusion of a CCK-receptor antagonist, CR 1409 (5 mg/kg/hr). Thus, the results of this study indicate that endogenous secretin rather than CCK is involved in the hormonal mechanism regulating the inhibition of gastric acid secretion by intestinal fat in rats.

Effect of short-termed pancreatic duct obstruction on the pancreatic subcellular organellar fragility and pancreatic lysosomal enzyme secretion in rabbits.

We studied the effect of short-term (3 h) pancreatic duct obstruction (PDO) on the exocrine pancreas and on the secretion of lysosomal enzymes into the pancreatic juice of rabbits during stimulation by pancreatic secretagogues. The following evaluations were made: serum amylase levels, pancreatic water content, pancreatic amylase, trypsinogen and cathepsin B content, and output of pancreatic enzymes and lysosomal hydrolases when stimulated by secretin and caerulein as well as the distribution of cathepsin B in subcellular fraction. Cellular fragility (LDH leakage from dispersed acini) and subcellular organellar fragility (cathepsin B leakage from lysosomes and malate dehydrogenase leakage from mitochondria) were also evaluated. PDO for 3 h plus secretin infusion caused a significant rise in serum amylase levels, pancreatic water content, and pancreatic amylase and trypsinogen content due to congestion of digestive enzymes during PDO. There was also a redistribution of cathepsin B from the lysosomal fraction to the zymogen fraction and increased cellular and subcellular organellar fragility. In normal rabbits and in those with only secretin infusion, caerulein stimulated the secretion of cathepsin B into pancreatic juice. Just after PDO, the secretion of cathepsin B, amylase and trypsinogen significantly decreased. By 24 h after PDO, the output of cathepsin B stimulated by caerulein and secretin had increased significantly. Amylase and trypsinogen output were also significantly increased at this stage, in both the secretin and caerulein fractions. These results indicate that the secretion of lysosomal enzymes into pancreatic juice is stimulated by gut hormones, such as caerulein, in the normal physiological state and in pathological states, such as PDO. These results also show an important role of increased cellular and subcellular organellar fragility in the pathogenesis of pancreatic injuries induced by PDO and augmented secretion of both lysosomal enzymes and pancreatic digestive enzymes in the recovery stage after PDO and their important roles at this stage. Lysosome enzymes also seem to play some physiological roles in the pancreatic ductal system in normal physiological states as well as their roles in pathological states, because cathepsin B can activate trypsinogen, and trypsin can activate many other enzymes.

Interaction between secretin and cholecystokinin-octapeptide in the exocrine rat pancreas in vivo and in vitro.

This study investigates the interaction between physiological doses of the synthetic gut hormones, cholecystokinin-octapeptide (CCK8) and secretin on pancreatic juice secretion in the anaesthetized rat and on amylase secretion and Ca2+ and Mg2+ mobilization in isolated pancreatic segments and acinar cells. CCK8 (150 pmol kg-1 h-1) and secretin (100 pmol kg-1 h-1) evoked marked time course increases in pancreatic juice flow, total protein output and amylase secretion in the anaesthetized rat when administered separately compared to saline controls. Simultaneous intravenous infusion of CCK8 and secretin did not yield either an additive response or a potentiation but instead it caused a decrease in secretory responses. Administration of either polymyxin B (10(-8) mol kg-1 h-1) or staurosporine (10(-8) mol kg-1 h-1), two protein kinase C inhibitors, simultaneously with both CCK8 and secretin caused a further decrease in all secretory parameters. Superfusing pancreatic segments with either CCK8 (10(-11) M) or secretin (10(-11) M) elevated amylase output compared to the smaller response with a combination of CCK8 and secretin. Combining staurosporine (10(-6) M) with CCK8 and secretin resulted in a further decrease in amylase output. CCK8 (10(-11) M) evoked a large increase in radiolabelled Ca2+ influx into pancreatic segments and elevated cytosolic free Ca2+ concentration ([Ca2+]i) in acinar cells loaded with the fluorescent dye, Fura-2. Secretin (10(-11) M) alone had no significant effect on Ca2+ mobilization but it markedly attenuated the increases in radiolabelled Ca2+ influx and [Ca2+]i elicited by CCK8. In superfused pancreatic segments CCK8 (10(-11) M) evoked a net efflux of Mg2+ whereas secretin (10(-11) M) induced a net uptake of Mg2+. Combining secretin with CCK8 also resulted in a net uptake of Mg2+. The results indicate that both Ca2+ and Mg2+ mobilization may be associated with the interaction between CCK8 and secretin in the rat pancreas.

The role of endogenous prostaglandins in hormone-stimulated pancreatic exocrine secretion

The authors have previously shown that neurotensin and secretin inhibit gastric acid secretion in the dog and that these actions are inhibited by the prostaglandin synthesis inhibitor indomethacin. Conversely, neurotensin and secretin share similar stimulatory effects on pancreatic exocrine secretion. In the present study, the effects of blockade of prostaglandin synthesis by indomethacin on neurotensin-, cholecystokinin-, and secretin-stimulated exocrine secretion are examined along with the effects of these same agents on the release of pancreatic polypeptide. The studies were performed on conscious dogs with chronic gastric and pancreatic cannulas. Dose-dependent increases in pancreatic exocrine secretion of water and bicarbonate were observed with IV infusion of neurotensin or secretin; however, inhibition of prostaglandin synthesis by indomethacin abolished this response. Protein secretion stimulated by either neurotensin or cholecystokinin was not affected by prostaglandin inhibition. Cholecystokinin and neurotensin infusion stimulated release of pancreatic polypeptide; only neurotensin-stimulated release of pancreatic polypeptide was inhibited by indomethacin treatment. It is concluded that intact prostaglandin synthesis is necessary for the actions of neurotensin and secretin (but not that of cholecystokinin) on pancreatic exocrine secretion of water and bicarbonate and for neurotensin- (but not cholecystokinin-) stimulated release of pancreatic polypeptide.

Secretagogue response of azaserine-induced rat pancreatic acinar tumors in vivo

This study investigates digestive and lysosomal enzyme secretion of azaserine-induced pancreatic acinar carcinomas in response to cholecystokinin in rats. After 15–20 months of treatment, 95% of the animals developed pancreatic acinar carcinomas encompassing more than 90% of the tissue. In anesthetized rats basal trypsin output was significantly elevated in the tumor group despite diminished fluid secretion. There was a linear correlation between tumor size and basal amylase and trypsin secretion. Intravenous infusion of cholecystokinin (25 IDU · kg−1 · h−1) induced a significantly lower secretion of fluid per gram pancreas, as well as decreased amylase and trypsin output, in the tumor group compared with the control group. Plasma amylase and lipase levels were significantly elevated in the tumor group under both basal and stimulated conditions. The output of the lysosomal enzymes β-d-glucuronidase and α-d-glucosidase was significantly increased in the tumor group under background secretin infusion. Additional cholecystokinin infusion caused a sharp increase in glucuronidase output in this group with only minimal increase in controls. Glucosidase output increased similarly in both groups. Amylase, lipase, and trypsin tumor tissue concentrations were markedly reduced by 85%, 90%, and 87%, respectively. It was concluded that the decreased secretory response of digestive enzymes may result from decreased synthesis, lowered storage capabilities, and/or a decreased/increased responsiveness to cholecystokinin. Increased glucuronidase secretion may reflect an augmented cell turnover of malignant tissue.

Zollinger-Ellison Syndrome

As clinical experience with patients with ZES has grown, increasing recognition has been made of the broad spectrum of symptoms associated with gastrinomas. Diarrhea and acid-induced esophageal injury have taken their place alongside chronic peptic ulcer disease as indications for screening for gastrinoma. Diagnostic testing should begin with fasting serum gastrin levels and should include intravenous secretin infusion if fasting serum levels of gastrin are nondiagnostic and the patient is not found to be hypochlorhydric. Tumor localization is critical to aid in the identification of patients with potentially curable localized disease. Preoperative evaluation utilizing CT scanning with intravenous contrast should be done early and should be supplemented by other imaging modalities as necessary. Exploratory laparotomy, including a thorough examination of the duodenum and perhaps intraoperative ultrasound, should be performed in all patients with sporadic gastrinoma who lack evidence of extensive metastatic disease on preoperative evaluation. By utilizing this approach, it is likely that at least 20% of patients with ZES can be cured. With the availability of the highly effective H(+)-K(+)-ATPase inhibitor omeprazole, excellent control of symptoms related to gastric acid hypersecretion can be expected. Patients with unresectable gastrinoma may thus avoid potentially morbid antisecretory surgery and be managed with a fairly simple medical regimen. Further developments in the chemotherapeutic management of these patients with unresectable disease should be forthcoming in the future.

Effect of the cholecystokinin-receptor antagonist lorglumide on pancreatic enzyme secretion stimulated by bombesin, food, and caerulein, giving similar plasma cholecystokinin concentrations in the dog.

This study was undertaken to determine the role of cholecystokinin in pancreatic enzyme secretion stimulated by bombesin and a meal by (a) comparing the pancreatic enzyme output during bombesin infusion and after a meal to output during caerulein infusion and (b) comparing the inhibitory effect of the cholecystokinin-receptor antagonist lorglumide (CR-1409) on enzyme output in response to bombesin and food with the response to caerulein. Bombesin (90 pmol/kg per h) and caerulein (30 pmol/kg per h) were infused into seven dogs in doses giving similar plasma cholecystokinin peak increments as a meal (mean (SEM) 6.8 (0.8), 6.3 (1.2), and 5.7 (0.8) pM, respectively), together with either saline or 2 mg/kg per h of lorglumide. A background infusion of synthetic secretin 20.5 pmol/kg per h was given in each experiment. In addition, gastric acid secretion was determined in the experiments with bombesin and caerulein infusion. Pancreatic protein responses to bombesin (1231 (247) mg/h) and food (1430 (220) mg/h) were similar to the responses to caerulein (1249 (201) mg/h). Lorglumide inhibited pancreatic protein output during stimulation with bombesin by 60%, after the meal by 45%, and during caerulein infusion by 68%. Pancreatic bicarbonate output by bombesin, caerulein, and food was inhibited by lorglumide by 28%, 40%, and 38%, respectively. In contrast, lorglumide significantly increased gastric acid secretion from 1.12 to 7.98 mmol/h during bombesin infusion and from 0.52 to 7.62 mmol/h during caerulein infusion. In conclusion, cholecystokinin plays an important part in the stimulation of pancreatic enzyme secretion by bombesin and a meal in conscious dogs and it is involved in the regulation of gastric acid during stimulation by infusions of caerulein and bombesin.

Pancreatic, Hepatic, and Duodenal Mucosal Bicarbonate Secretion during Infusion of Secretin and Cholecystokinin: Evidence of the Importance of Hepatic Bicarbonate in the Neutralization of Acid in the Duodenum of Anaesthetized Pigs

The effect of infusion of secretin alone or in combination with cholecystokinin (CCK) on pancreatic, hepatic, and duodenal mucosal bicarbonate secretion was studied in anaesthetized pigs. After laparotomy, catheters were inserted into the common bile duct, the pancreatic duct, and both ends of the duodenum. Pancreatic, hepatic, and duodenal mucosal secretions were collected during intraportal infusion of increasing doses of secretin, either alone or in combination with CCK. During infusion of secretin in doses that caused physiologic increases in plasma secretin concentrations the liver produced significantly more bicarbonate than the pancreas. A physiologic dose of CCK augmented the effect of secretin on both hepatic and pancreatic bicarbonate secretion, but the hepatic production of bicarbonate was still larger than the pancreatic production. Neither secretin alone nor secretin combined with CCK caused any changes in duodenal mucosal bicarbonate secretion. These results suggest that the liver plays an important role in the neutralization of acid in the duodenum.