Action of atropine on the pancreatic secretory response to secretin before and after cutting the extrinsic nerves of the pancreas in dogs

In two sets of dogs with gastric and pancreatic fistulas, we studied the effect of atropine on the pancreatic secretory response to intravenous secretin before and after cutting the extrinsic nerves of the pancreas, i.e., celiac and superior mesenteric ganglionectomy alone or truncal vagotomy plus celiac and superior mesenteric ganglionectomy. Neither truncal vagotomy alone nor ganglionectomy alone, nor the two together, altered the incremental bicarbonate response to secretin. Irrespective of the degree of integrity of the extrinsic vagal and splanchnic innervation of the pancreas, intravenous atropine (14 nmol/kg X h) significantly (p less than 0.05) depressed the incremental bicarbonate responses to the two lowest (5.2 and 10.3 pmol/kg X h) doses of secretin by 85% and 61%, respectively, but had no significant effect on responses to high doses. We conclude that the pancreatic bicarbonate response to secretin, and the action of atropine on that response, are independent of an intact extrinsic innervation of the gland. The observation of the persistent inhibitory action of atropine after extrinsic denervation of the pancreas is compatible with the hypothesis that endogenous cholinergic activity augments the pancreatic bicarbonate response to secretin.     

Pancreatic polypeptide response to a meal before and after cutting the extrinsic nerves of the upper gastrointestinal tract and the pancreas in the dog

The role of the sympathetic and parasympathetic innervation in the release of pancreatic polypeptide (PP) basally and in response to a meal was studied after stepwise extrinsic denervation of the pancreas and the upper gastrointestinal tract in conscious dogs with gastric fistulae. One set of seven dogs was fed a meat meal (35 g/kg body weight) before and after truncal vagotomy and after truncal vagotomy plus celiac and superior mesenteric ganglionectomy, ie, extrinsic denervation of the pancreas and the upper gastrointestinal tract. In another set of six dogs, only ganglionectomy was performed. Experiments were repeated in the presence of atropine (50 g/kg body weight, given as an intravenous bolus 60 min prior to the meal). Truncal vagotomy significantly (P<0.05) reduced the postprandial 120-min integrated plasma PP response (IPPPR) by 84% as compared to the prevagotomy response. Before truncal vagotomy, atropine significantly reduced the IPPPR by 57%. After truncal vagotomy, atropine completely abolished the residual PP response. Additional celiac and superior mesenteric ganglionectomy did not alter the IPPPR already reduced by truncal vagotomy. With the vagus nerves intact, ganglionectomy alone had no effect on the IPPPR whether or not atropine was given. These findings indicate that (1) the splanchnic nerves do not play a significant role in postprandial PP release and (2) that the vagus nerves are important mediators of the response to a meal. The effect of atropine on postprandial PP release after truncal vagotomy may be due to interruption of short enteropancreatic reflexes, suppression of the intrinsic cholinergic activity of the pancreas, or inhibition of hormonally induced PP release.     

Pancreatic secretory response to intravenous caerulein and intraduodenal tryptophan studies: before and after stepwise removal of the extrinsic nerves of the pancreas in dogs

In two sets of 6 dogs with gastric and pancreatic fistulas, we studied the effect of atropine (14 nmol/kg.h i.v.) on the pancreatic secretory response to intravenous caerulein and to intraduodenal perfusion with tryptophan (both given with a secretin background) before and after stepwise removal of the extrinsic nerves of the pancreas, i.e., celiac and superior mesenteric ganglionectomy alone or truncal vagotomy alone and truncal vagotomy plus celiac and superior mesenteric ganglionectomy. Atropine significantly (p less than 0.05) depressed the protein output in the basal state and in response to secretin at each stage of innervation. The incremental protein response to caerulein was not altered by the various denervation operations nor by atropine. Truncal vagotomy alone significantly decreased the incremental protein response to low (0.12, 0.37, and 1.1 mmol/h) but not high loads of tryptophan. Ganglionectomy in combination with vagotomy did not further depress the incremental protein response to low loads of tryptophan. Atropine significantly reduced the incremental protein response to low loads of tryptophan only in intact innervated animals. Ganglionectomy alone did not alter the incremental protein response to any load of tryptophan. Ganglionectomy, truncal vagotomy, and atropine did not alter basal or tryptophan-stimulated levels of plasma cholecystokininlike immunoreactivity. We conclude that (a) neither the extrinsic nor the intrinsic cholinergic pancreatic nerves modulate the protein response to caerulein; (b) the sympathetic pancreatic nerves do not mediate the response to tryptophan; (c) the protein response to intraduodenal tryptophan is at least in part mediated by long, cholinergic, enteropancreatic reflexes with both afferent and efferent fibers running within the vagus nerves; and (d) release of cholecystokinin by intestinal tryptophan is not under cholinergic or splanchnic control.     

Intrinsic pancreatic nerves after mechanical denervation of the extrinsic pancreatic nerves in dogs.

Little is known about the influence of cutting the extrinsic pancreatic nerves on the morphology and function of the intrapancreatic nerves in dogs. For this reason, intrapancreatic nerves of mongrel dogs were studied, using electron microscopy and immunohistochemistry, after truncal vagotomy, after celiac and superior mesenteric ganglionectomy, and after a combination of both operations, i.e., removing all extrinsic nerves of the pancreas. Dogs with intact extrinsic and intrinsic pancreatic nerves served as controls. Studies were performed 1-2 weeks and up to 5 months after one or both denervation procedures. For immunohistochemical and electron microscopic studies the animals were perfused with glutaraldehyde-formaldehyde-picric acid solution and the tissue was embedded in Epon or paraffin. Both immunohistochemical and electron microscopic studies revealed that signs of degenerating intrapancreatic nerves occurred only in the early phase (up to 30 days) after operation. After 60 days, hypertrophy of pancreatic nerve fibers was observed. The most striking finding was that the integrity of the intrapancreatic ganglia and nerves was almost preserved after complete extrinsic denervation. In controls there was a strong intrapancreatic innervation with vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine (PHI), substance P (SP), and neuropeptide Y (NPY) nerves. SP and NPY-nerves significantly decreased after the different denervation procedures, but the other peptidergic nerves were not altered by truncal vagotomy, ganglionectomy, or the combination of both procedures. We conclude that the dog pancreas contains extensive intrinsic peptidergic nerves, which, with the exception of SP and NPY-nerves, are greatly independent of the integrity of the extrinsic nerves.     

Effect of partial versus complete pancreatic denervation on pancreatic secretion

The aim of this study is to compare the effect of various stimuli on pancreatic secretion in two groups of dogs, one undergoing interruption of the cholinergic and adrenergic branches to the pancreas (long arc reflexes), and the second group undergoing total denervation of the pancreas by its isolation from stomach and duodenum (short arc reflexes). Stimulation of pancreatic secretion was accomplished by (a) hormonal, by i.v. secretin and CCK/PZ and (b) reflex stimulation by intraduodenal administration of fat (Na oleate) or amino acids (Aminosyn). After a few weeks of collected data in stimulated controls, the dogs were divided into two groups: (A) Four dogs underwent proximal truncal vagotomy, celiac ganglionectomy, and stripping of the common hepatic and gastroduodenal arteries for 2-3 cm. (B) Four dogs underwent the same procedures, but in addition the pancreas was dissected away from its vascular and nervous attachments to the duodenal wall and pyloric region, as well as from its mesenteric and peritoneal attachments. All animals were then tested with secretin, Cholecystokinin/pancreozymin (CCK/PZ), intraduodenal fat, and intraduodenal amino acids. The data obtained indicate that secretion of pancreatic bicarbonate is dependent on intact local duodeno-pancreatic nervous reflexes. Fat and amino acids stimulate the secretion of bicarbonate only when the attachments of the pancreas to the stomach and duodenum are intact. Stimulation by secretion or CCK, being humoral-hormonal mediators, appears not to be affected by the local denervation.     

Effects of autonomic denervation on canine exocrine pancreatic secretion and blood flow

The effect of autonomic denervation on the exocrine pancreatic secretion and blood flow was studied in a group of dogs. Pancreatic secretion was collected and analyzed for volume and bicarbonate by direct cannulation of the main papilla through a duodenotomy prior to and following truncal vagotomy and celiac plexus denervation. Pancreatic blood flow was determined by the radioisotope distribution method (141Ce). Truncal vagotomy causes a reduction in pancreatic secretion of volume and bicarbonate by 25-30%, while celiac denervation caused a reduction of 70% in the secretion. The mean baseline pancreatic blood flow was 0.5 ml/g pancreas/min. Truncal vagotomy did not cause any significant flow changes, while celiac denervation caused a significant increase in blood flow of 350% (to 1.75 ml/g/min). These results suggest that both the parasympathetic and the sympathetic system affect pancreatic secretion independently of their effect upon pancreatic blood flow.     

Effects of autonomic denervation on canine exocrine pancreatic secretion and blood flow

Summary The effect of autonomic denervation on the exocrine pancreatic secretion and blood flow was studied in a group of dogs. Pancreatic secretion was collected and analyzed for volume and bicarbonate by direct cannulation of the main papilla through a duodenotomy prior to and following truncal vagotomy and celiac plexus denervation. Pancreatic blood flow was determined by the radioisotope distribution method (¹⁴¹Ce). Truncal vagotomy causes a reduction in pancreatic secretion of volume and bicarbonate by 25–30%, while celiac denervation caused a reduction of 70% in the secretion. The mean baseline pancreatic blood flow was 0.5 ml/g pancreas/min. Truncal vagotomy did not cause any significant flow changes, while celiac denervation caused a significant increase in blood flow of 350% (to 1.75 ml/g/min). These results suggest that both the parasympathetic and the sympathetic system affect pancreatic secretion independently of their effect upon pancreatic blood flow.     

Pancreatic secretory response to intraileal amino acids: studies in dogs with an in situ neurally isolated ileum.

BACKGROUND: Intraileal carbohydrates and lipids affect the pancreatic exocrine secretion, but the effect of intraileal amino acids and the role of the extrinsic nerves of the ileum as mediators of the pancreatic bicarbonate and enzyme output are unknown. METHODS: Four dogs underwent total extrinsic denervation of the entire ileum. Thomas-like cannulas were placed into the stomach, duodenum (to collect pure pancreatic juice), and at the jejuno-ileal junction. Eight neurally intact control dogs received only the three fistulas. After recovery, in both sets of dogs, dose-response studies of the pancreatic secretory response to intraileal infusion with graded loads of tryptophan (0.12-10.0 mmol/h) were performed, given against an intravenous (iv) background of secretin (20.5 pmol/kg/h) and cerulein (29.6 pmol/kg/h). On separate days, control experiments with intraileal infusion of 0.15 M NaCl were performed. RESULTS: In both sets of dogs, iv secretin plus cerulein significantly (p < 0.05) increased pancreatic bicarbonate and protein output above basal. Intraileal tryptophan caused a dose-dependent decrease in the pancreatic bicarbonate and protein response to secretin plus cerulein. In the dogs with denervated ileum, this inhibition was significantly stronger than in the intact animals. In both sets of dogs, the 225-min integrated bicarbonate (IBR) and protein response (IPR) to all loads of tryptophan were significantly lower than in control experiments. Both IBR and IPR were significantly lower in the denervated as compared with the intact animals. CONCLUSIONS: 1) Extrinsic denervation of the entire ileum is a valuable preparation to study the role of nerves in the control of pancreatic exocrine secretion; 2) both in the intact and denervated animals the amino acid tryptophan induces an "ileal brake" of the hormonally stimulated pancreatic bicarbonate and protein output; 3) the extrinsic nerves of the ileum are probably not the dominant mediators of the inhibitory action of intraileal tryptophan but rather counteract this effect.     

Neural pathways for the release of gastrin,cholecystokinin, and pancreatic polypeptide after a meal in dogs

We have measured gastrin, cholecystokinin (CCK), and pancreatic polypeptide (PP) release after a meal in normal dogs under basal conditions and during atropine infusion, and after various neural sections. Denervation of the gastric antrum (antral vagotomy) abolished the early part of the gastrin response to food. Truncal vagotomy, celiac ganglionectomy, and atropine reduced the early release of CCK, which occurred before the start of gastric emptying, suggesting that a neural, cholinergic mechanism may release CCK immediately after a meal. PP release was abolished by truncal vagotomy, and also by antral vagotomy. As no direct pathways are known between the antrum and the pancreas, this suggests either that antral afferents are essential for this response or that vagally mediated hormone release from the antrum mediates PP release.     

Response of Heidenhain Pouch to Histamine,Gastrin and Feeding before and after Truncal Vagotomy in Dogs

Dogs with both gastric fistulas of the main stomach and Heidenhain pouches were studied before and after transthoracic truncal vagotomy. Confirming earlier studies in dogs with gastric fistulas alone, truncal vagotomy abolished the acid secretion in response to 2-deoxy-D-glucose (2-DG) and depressed the response to submaximal doses of exogenous gastrin or histamine but did not alter the maximal responses to gastrin or histamine. Effects of truncal vagotomy on acid secretion from the Heidenhain pouches: a) response to 2-DG with the gastric fistulas open was abolished, b) submaximal, but not maximal, responses to histamine were decreased, c) submaximal and maximal responses to exogenous gastrin were markedly increased, and d) response to feeding was markedly increased.     

Pancreatic secretory response to intraileal amino acids

Summary Background: Intraileal carbohydrates and lipids affect the pancreatic exocrine secretion, but the effect of intraileal amino acids and the role of the extrinsic nerves of the ileum as mediators of the pancreatic bicarbonate and enzyme output are unknown. Methods: Four dogs underwent total extrinsic denervation of the entire ileum. Thomas-like cannulas were placed into the stomach, duodenum (to collect pure pancreatic juice), and at the jejuno-ileal junction. Eight neurally intact control dogs received only the three fistulas. After recovery, in both sets of dogs, dose-response studies of the pancreatic secretory response to intraileal infusion with graded loads of tryptophan (0.12–10.0 mmol/h) were performed, given against an intravenous (iv) background of secretin (20.5 pmol/kg/h) and cerulein (29.6 pmol/kg/h). On separate days, control experiments with intraileal infusion of 0.15 M NaCl were performed. Results: In both sets of dogs, iv secretin plus cerulein significantly (p<0.05) increased pancreatic bicarbonate and protein output above basal. Intraileal tryptophan caused a dose-dependent decrease in the pancreatic bicarbonate and protein response to secretin plus cerulein. In the dogs with denervated ileum, this inhibition was significantly stronger than in the intact animals. In both sets of dogs, the 225-min integrated bicarbonate (IBR) and protein response (IPR) to all loads of tryptophan were significantly lower than in control experiments. Both IBR and IPR were significantly lower in the denervated as compared with the intact animals. Conclusions: 1) Extrinsic denervation of the entire ileum is a valuable preparation to study the role of nerves in the control of pancreatic exocrine secretion; 2) both in the intact and denervated animals the amino acid tryptophan induces an “ileal brake” of the hormonally stimulated pancreatic bicarbonate and protein output; 3) the extrinsic nerves of the ileum are probably not the dominant mediators of the inhibitory action of intraileal tryptophan but rather counteract this effect.     

Gastric acid and pancreatic polypeptide responses to modified sham feeding. Effects of truncal and parietal cell vagotomy.

The effects of truncal vagotomy and parietal cell vagotomy on gastric acid secretion and plasma gastrin and pancreatic polypeptide release were studied in 28 duodenal ulcer patients under basal conditions and after modified sham feeding and infusion of pentagastrin (2 micrograms/kg/h). Before vagotomy gastric acid output in response to modified sham feeding was significantly higher than basal acid secretion in all subjects tested and reached about 45% of the pentagastrin maximum. No difference in the increase in acid response, or in the pancreatic polypeptide response to modified sham feeding was found between patients with high and low basal secretion. Plasma gastrin concentration was unaltered by modified sham feeding before and after truncal vagotomy or parietal cell vagotomy, although after vagotomy it tended to reach higher values than before this procedure. After truncal vagotomy, basal pancreatic polypeptide concentration was decreased and modified sham feeding-induced pancreatic polypeptide increment was completely eliminated. Four weeks after parietal cell vagotomy, the modified sham feeding-induced increment in plasma pancreatic polypeptide was significantly decreased and observed only in seven of 12 patients. Four to five years after parietal cell vagotomy all subjects responded to modified sham feeding with pancreatic polypeptide increment similar to that before vagotomy and in three of 12 patients acid response to modified sham feeding was seen. This study indicates that truncal vagotomy eliminates gastric acid and plasma pancreatic polypeptide responses to vagal excitation while parietal cell vagotomy abolishes gastric acid response and reduces temporarily the pancreatic polypeptide response to modified sham feeding (possibly because of transient impairment of the vagal innervation of the pancreas). (2) A high ratio of basal to maximal acid output in non-operated duodenal ulcer patients is not associated with a low acid response to modified sham feeding, nor with a high pancreatic polypeptide concentration, and (3) Restitution of the pancreatic polypeptide response to modified sham feeding five years after parietal cell vagotomy does not indication ineffective denervation of the parietal cells.     

Gastric and Pancreatic Sympathetic Denervation in the Rat

The extirpation of the coeliac and superior mesenteric ganglia was found to be a simple and effective method of achieving complete adrenergic denervation of the stomach and pancreas in the rat. Thus, using the formaldehyde fluorescence technique, no remaining adrenergic nerves in these organs could be found after ganglionectomy. The vagus nerves did not significantly contribute to the adrenergic innervation of the stomach and pancreas. Chemical methods revealed minute amounts of noradrenaline in the pancreatic tissue even after complete ganglionectomy. The cellular source of this catecholamine is unknown. Sympathetic denervation of the stomach did not change the gastric acid secretory pattern, as studied with chronic gastric fistula rats.     

The cephalogastric phase of the pancreatic response to food in the dog

We studied post-meal pancreatic secretion and gastrin release in conscious dogs with duodenal Thomas cannulas. Normal dogs were tested in physiological conditions and with an i.v. infusion of atropine 20 micrograms/kg/h or secretin 0.5 CU/kg/h. The responses were also studied after antral and truncal vagotomy. In the early phase (0-20 min) of the response, before gastric emptying started, antral vagotomy reduced fluid and protein outputs, and truncal vagotomy reduced them still more. Atropine reduced only the protein response. Gastrin release reached a peak after 20-25 min. After antral and truncal vagotomy, gastrin release was reduced within 10 min after the meal. Late-phase (greater than 20 min) pancreatic secretion depended on the presence of chyme in the duodenum. The effects of atropine and antral vagotomy in the cephalogastric phase could be explained by antropancreatic reflexes stimulating fluid secretion (atropine-resistant pathway) and protein output (atropine-sensitive pathway).     

Effect of two types of beta-adrenergic blockade on gastric acid secretion during pentagastrin stimulation in non-vagotomized and in vagotomized gastric fistula dogs.

The effect of beta-adrenoceptor blockade by propranolol and practolol on submaximally pentagastrin-stimulated gastric acid secretion was studied in conscious non-vagotomized and in vagotomized gastric fistula dogs. Propranolol (0.5 mg/kg) intravenously augmented gastric acid output in vagotomized dogs, more after truncal and selective vagotomy than after parietal cell vagotomy. Vagally innervated dogs also showed an increase, but to a lesser degree and not statistically significant. The increase restored the acid output to preoperative levels in the vagotomized dogs. Practolol (1.0 mg/kg) intravenously resulted in a slight and insignificant increase in acid output in dogs with truncal vagotomy and had only a negligible effect in vagally innervated dogs and after selective and parietal cell vagotomy. It is concluded that propranolol augments pentagastrin-stimulated acid output in vagotomized dogs, and this augmentation was most pronounced in the totally vagotomized stomach. Practolol had minor influence on gastric acid secretion. This effect of the two beta-blocking agents indicates that beta 2-blockade is most important for the secretory augmentation. The restoration of postvagotomy acid secretion to preoperative levels suggests that adrenergic influence is important for the decrease in pentagastrin-stimulated acid secretion after vagotomy.     

Effects of truncal vagotomy and antrectomy on bombesin-stimulated pancreatic secretion,release of gastrin,and pancreatic polypeptide in the anesthetized dog

The short-term effects of truncal vagotomy and antrectomy on bombesin-stimulated pancreatic secretion and release of gastrin and pancreatic polypeptide (PP) were studied in 18 anesthetized dogs. Together with an intravenous infusion of secretin (250 ng/kg/hr) bombesin (500 ng/kg/hr) was given before and after truncal vagotomy, antrectomy, and sham operation (N=6 dogs per group). Peak incremental pancreatic protein output in procedures (tachyphylaxis). Neither truncal vagotomy nor antrectomy significantly altered the pancreatic protein response to bombesin when compared with sham operation. Bombesin produced a mean 1-hr increase over basal of 196 pM for gastrin, which was abolished by antrectomy but not appreciably affected by truncal vagotomy and sham operation. The mean 1-hr increment (207 pM) for PP in response to bombesin was not changed by truncal vagotomy, antrectomy, and sham operation. This study shows in the anesthetized dog that exogenous bombesin stimulates release of PP as well as gastrin; that the release of gastrin by bombesin is not vagally dependent; that neither truncal vagotomy nor antrectomy alter the release of PP by bombesin; and that the action of bombesin on pancreatic protein secretion does not depend on release of gastrin or on intact vagal nerves.Parts of this paper have been presented at the 12th European Pancreatic Club Meeting, Copenhagen, Denmark, October 11–13, 1979, and at the 3rd International Symposium on Gastrointestinal Hormones, Cambridge, England, September 15–18, 1980.     

Influence of vagotomy on bicarbonate secretion in the rat proximal duodenum.

The influence of vagotomy on bicarbonate secretion in the proximal duodenum was assessed in rats receiving truncal, hepatoduodenal and gastric vagotomy. Two weeks after vagotomy, animals fasted for 24 hr were subjected to laparotomy under urethane anesthesia. A proximal duodenal loop excluding the outlet of the common bile duct was prepared as part of an airtight extracorporeal perfusion circuit. The circuit was filled with a bathing solution at pH 4.5 and which was perfused at a rate of 10 ml/min at a constant temperature of 37 degrees C. The pH and CO2 tension of the bathing solution were determined using microelectrodes, and bicarbonate secretion was calculated from the pH and CO2 tension data by the Henderson-Hasselbalch equation. The bicarbonate secretion at the first portion of the duodenum over a 60-min period was significantly higher in the truncal and hepatoduodenal vagotomy groups than in the control group. However, there was no significant difference between the gastric vagotomy and control groups. Furthermore, no significant difference was noted between the truncal and hepatoduodenal vagotomy groups. Since bicarbonate secretion was increased by hepatoduodenal vagotomy, the hepatoduodenal branch of the vagus nerve appeared to inhibit bicarbonate secretion at the first portion of the duodenum.     

Effect of Vagotomy on the Canine Pancreatic Secretion after Feeding

The effect of vagotomy on the external pancreatic secretion in response to a meat meal was investigated in 5 dogs with duodenal and gastric Thomas cannulas. Precautions were taken to maintain the normal regulation of neutrality in the duodenum during the post-prandial period. The gastric acid secretion was determined in some experiments. After vagotomy the secretion of gastric acid and pancreatic fluid and bicarbonate were reduced to the same degree, about 85 %, while the pancreatic secretion of protein was only reduced 57 %. Cholinergic stimulation with Urecholine increased the pancreatic secretion of fluid and bicarbonate to pre-vagotomy levels. The protein secretion did not attain that level, indicating an impaired protein secretion.     

Influence of vagotomy on bicarbonate secretion in the rat proximal duodenum

The influence of vagotomy on bicarbonate secretion in the proximal duodenum was assessed in rats receiving truncal, hepatoduodenal and gastric vagotomy. Two weeks after vagotomy, animals fasted for 24 hr were subjected to laparotomy under urethane anesthesia. A proximal duodenal loop excluding the outlet of the common bile duct was prepared as part of an airtight extracorporeal perfusion circuit. The circuit was filled with a bathing solution at pH 4.5 and which was perfused at a rate of 10 ml/min at a constant temperature of 37°C. The pH and CO₂ tension of the bathing solution were determined using microelectrodes, and bicarbonate secretion was calculated from the pH and CO₂ tension data by the Henderson-Hasselbalch equation. The bicarbonate secretion at the first portion of the duodenum over a 60-min period was significantly higher in the truncal and hepatoduodenal vagotomy groups than in the control group. However, there was no significant difference between the gastric vagotomy and control groups. Furthermore, no significant difference was noted between the truncal and hepatoduodenal vagotomy groups. Since bicarbonate secretion was increased by hepatoduodenal vagotomy, the hepatoduodenal branch of the vagus nerve appeared to inhibit bicarbonate secretion at the first portion of the duodenum.     

Exocrine pancreatic function in dogs with denervated pancreas

There is strong evidence that the vagus nerve plays an important role in exocrine pancreatic secretion. In the present study we examined the effect of total extrinsic denervation of the pancreas on exocrine pancreatic secretion to different stimuli in dogs. In the experiments we used the model of the orthotopic autotransplanted dog pancreas as described by Debas et al. Denervation of the gland did not significantly alter water and bicarbonate response to secretin. The dose-response curve of caerulein showed the denervated pancreas as sensitive as the intact gland. However, autotransplantation of the pancreas caused a significant decrease (p less than 0.05) in protein secretion during intraintestinal L-tryptophan in increasing doses. Furthermore, bicarbonate and protein secretion after food intake was significantly decreased in the denervated pancreas (protein: peak levels 380 mg/15 min and 135 mg/15 min; bicarbonate: 3.2 mEq/15 min and 1.4 mEq/15 min) (p less than 0.02). From our data we conclude that the denervated pancreas is as sensitive as the intact pancreas to stimulation by exogenous secretin and caerulein, whereas denervation of the pancreas causes an important influence in the intestinal phase of pancreatic secretion.