Pancreatic Exocrine Secretion In Dogs Research Articles

Long-term bile diversion enhances basal and duodenal oleate-stimulated pancreatic exocrine secretion in dogs.

There have been no previous reports whether long-term bile diversion enhances pancreatic exocrine secretion. The aim of this study was to elucidate the effect of long-term bile diversion on pancreatic exocrine secretion. Four mongrel dogs were prepared for chronic gastric and pancreatic fistulas and received intraduodenal sodium oleate infusion (controls). These dogs, then underwent diversion of bile from the intestines by ligating the common bile duct and interposing a segment of jejunum between the gallbladder and the urinary bladder (total biliary diversion [TBD]). After three weeks, the dogs received an identical sodium oleate infusion. TBD augmented basal pancreatic exocrine secretion compared with controls (4.4-fold increase in basal flow volume; 9.0-fold increase in bicarbonate output; and 3.3-fold increase in protein output). Likewise, TBD augmented oleate-stimulated exocrine secretion (2.0-fold increase in cumulative flow volume; 2.6-fold increase in bicarbonate output; and 1.4-fold increase in protein output). TBD also augmented basal and oleate-stimulated plasma cholecystokinin levels. Administration of a Cholecystokinin-A receptor antagonist (loxiglumide) after TBD reduced the flow volume and bicarbonate output to the control levels, and the protein output to less than a half of the control level. Long-term bile diversion enhances basal and oleate-stimulated pancreatic exocrine secretion, at least partly via increased cholecystokinin secretion.

Effects of the Amount and Type of Dietary Fat on Exocrine Pancreatic Secretion in Dogs after Different Periods of Adaptation

Mongrel dogs were fed, from weaning to 6 months of age, on one of two 9% lipid diets that differed only in the type of fat content (sunflower oil or virgin olive oil) to study their effects on exocrine pancreatic secretion, in the basal period and in response to food. In addition, the results were compared with those obtained in a previous work performed by us on dogs adapted for 8 months to diets containing a higher (15%) amount of the same dietary fats to further evaluate the influence of the amount of dietary fat and the length of the adaptation period. The results from the present study show that both the volume and bicarbonate secreted in the absence of stimuli are unaffected by the quality of dietary fat. In contrast, in response to food, the pancreatic juice flow and the bicarbonate output were significantly higher in the group of animals given the sunflower oil diet. The differences seem to be related with the oleic acid content in the diets and the effectiveness of this fatty acid in triggering the release of inhibitory peptides such as pancreatic polypeptide and peptide YY. The comparison between the results from our present and previous studies supports the afore-mentioned hypothesis and confirms the existence of a clear influence of the amount and type of dietary fat, especially the oleic acid content, upon the pancreatic response to food, without ruling out a role for the duration of the adaptation period.

Feedback regulation of exocrine pancreatic secretion in dogs.

Important basic physiological mechanisms of exocrine pancreas secretion were delineated in a canine model. However, dogs have been considered unsuitable for the study of the controversial feedback regulation of exocrine pancreas secretion. The present study reveals a marked modification of pancreas secretion following the intraduodenal instillation of lipase: The postprandial lipase secretion decreases from 2,421 U x 180 min-1 to 1,490 U x 180 min-1, but simultaneously determined cholecystokinin (CCK) concentrations in plasma do not increase under these circumstances. The intraduodenal application of a protease inhibitor (800 mg camostate) significantly stimulates the secretion of the exocrine pancreas in the fasting dog: After 15 min the protein release increased to 133 +/- 30 mg. Intravenous atropine blocks this increase. The plasma concentrations of CCK are not significantly influenced. These results in our canine model show that the secretory activity of the exocrine pancreas depends on the intraduodenal enzyme content. CCK is irrelevant in this context.

Role of neurotensin in the regulation of exocrine pancreatic secretion in dogs

A potential physiological function of the regulatory gastrointestinal peptide neurotensin (NT) is the stimulation of exocrine pancreatic secretion. We investigated therefore whether immunoneutralization of the postprandially circulating peptide, intravenous application of either atropine or the highly specific CCK receptor antagonist, L-364,718, could influence neurotensin-mediated pancreatic secretion in dogs. The use of CCK receptor antagonist (0.1 mg kg −1 intraduodenally) inhibited postprandial and NT-mediated exocrine pancreatic secretion. The integrated postprandial protein secretion fell from 31 ± 1.6 to 23 ± 2.1 g 180 min −1 while the corresponding values in response to i.v.-NT (postprandial neurotensin concentration course was imitated by the infusion of 50 pmol kg h −1 NT) fell from 22 ± 1.9 to 7.5 ± 0.8 g 180 min −1. Immunoneutralization of postprandial NT led to a simultaneous significant reduction in postprandial pancreatic secretion (integrated protein release 31 ± 1.6 and 15.5 ± 1.4 g 180 min −1 respectively). The i.v. application of atropine lowered NT-mediated pancreatic secretion (e.g., protein output) from 22 ± 1.9 to 7.1 ± 7.1 ± 0.9 g 180 min −1. We conclude that NT plays an important role in the endocrine regulation of exocrine pancreatic secretion. This influence could be mediated by a CCK-dependent cholinergic mechanism.

Gastrin-Releasing Peptide and Cholecystokinin in the Regulation of Exocrine Pancreatic Secretion in Dogs

Exocrine pancreatic secretion in conscious dogs is significantly stimulated by the intravenous application of small doses of gastrin-releasing peptide (GRP; 30 pmol x kg-1 x h-1). There is no increase of the GRP concentrations in peripheral blood which is also the case under physiological postprandial conditions. There is also no increase in the peripheral cholecystokinin (CCK) concentrations, in contrast to previous reports. Nevertheless other CCK-related mechanisms may play an important role, since the administration of the highly specific CCK receptor antagonist MK-329 causes a marked reduction of the GRP-induced exocrine pancreatic secretion.

Inhibition of exocrine pancreatic secretion in dog by peptide YY is mediated by PYY-preferring Y 2 receptors

Inhibition of exocrine pancreatic secretion in dog by peptide YY is mediated by PYY-preferring Y 2 receptors

Total denervation of the pancreas does not alter the pancreatic polypeptide-induced inhibition of pancreatic exocrine secretion in dogs

Pancreatic polypeptide (PP) is a potent inhibitor of pancreatic exocrine secretion in vivo. The mechanism of pancreatic inhibition by PP is unknown, but the absence of PP receptors on pancreatic exocrine cells makes a direct effect of this hormone on the gland unlikely. In this study, we investigated the hypothesis that PP exerts its inhibitory effect via extrinsic neural pathways. Ten dogs with gastric and pancreatic fistulas were given an intravenous infusion of 250 ng/kg-1 h-1 secretin and 50 ng/kg-1 h-1 caerulein over 3 h. One hour after starting the infusion, 400 pmol kg-1 h-1 porcine PP were administered over 1 h. Pancreatic bicarbonate and protein secretions were measured. Later, the pancreas was extrinsically denervated. PP infusion decreased bicarbonate secretion in the intact gland by 47% and in the denervated pancreas by 57%. Protein secretion was diminished by exogenous PP by 31% in the intact and by 44% in the denervated pancreas. Despite pancreatic denervation, PP still exerted a significant inhibitory effect. Atropine infusion completely blocked the inhibitory effect of PP on caerulein-stimulated pancreatic protein secretion both in the intact and denervated pancreas and of secretion-evoked bicarbonate output in the denervated gland. We conclude that the inhibitory action of the hormone is not mediated via extrinsic neural pathways of the pancreas, but PP may exert its effect via intrinsic atropine-sensitive mechanisms.

Effects of the cyclic nucleotide phosphodiesterase inhibitors, rolipram, 3-isobutyl-1-methylxanthine, amrinone and zaprinast, on pancreatic exocrine secretion in dogs

The effects of the cyclic phosphodiesterase (PDE) inhibitors, rolipram, 3-isobutyl-1-methylxanthine (IBMX), amrinone and zaprinast on pancreatic exocrine secretion were investigated in anesthetized dogs. Rolipram (1–30 nmol), IBMX (44–440 nmol) or zaprinast (1–10 μmol) injected i.a. elicited a dose-dependent increase in the secretion of pancreatic juice, but amrinone (up to 53 μmol) did not. The bicarbonate concentration in pancreatic juice was increased and the protein concentration was decreased by rolipram and IBMX, but neither was affected by zaprinast. Rolipram elicited more than the respective additive secretory response when added together with secretin, although the stimulatory effects of CCK-8 with rolipram were additive. Rolipram and IBMX, but not zaprinast, increased cyclic AMP concentration but did not affect cyclic GMP concentration. These results suggest that rolipram, IBMX and zaprinast have direct secretory properties on pancreatic exocrine glands of the dog, which may be mediated through the increase of intracellular cyclic AMP concentration, by inhibiting PDE activity. Furthermore, the pancreatic PDE enzyme in the dog pancreas may be mainly a type IV.

Effect of synthetic porcine neuropeptide Y (NPY) on splanchnic blood flows and Exocrine pancreatic secretion in dogs

This study examined the effect of synthetic porcine neuropeptide Y on the splanchnic blood flows and the exocrine pancreatic secretion in dogs. Graded doses of neuropeptide Y (0.1-5 microg/kg, intravenous) caused dose-dependent reduction of the secretin-stimulated exocrine pancreatic secretion and of the blood flows in the superior mesenteric artery, the portal vein, and the pancreatic tissue. Neuropeptide Y at 5 microg/kg reduced the blood flows to 45.9 +/- 13.3% (superior mesenteric artery), 63.0 +/- 10.5% (portal vein), and 77.9 +/- 4.8% (pancreatic tissue), respectively. This dose also reduced secretin-stimulated pancreatic juice volume and CCK-8 plus secretin-stimulated protein output to 65.2 +/- 9.3 and 63.3 +/- 14.0%, respectively. This study shows a potent vasoconstrictor effect of neuropeptide Y on splanchnic vessels. Neuropeptide Y also inhibited exocrine pancreatic secretion in a significant correlation with the reduction in pancreatic tissue blood flow, which suggests that reduction in the blood flow may be one of the possible mechanisms of the inhibitory action of neuropeptide Y on exocrine secretion.

POTENTIATED EFFECT OF VAGAL STIMULATION AND HORMONAL AGENTS ON PANCREATIC EXOCRINE SECRETION IN DOGS

Chronic experiments were made on eighteen dogs with Thomas pancreatic fistula and gastric fistula. Both in chronic and acute experiments the degenerated right cervical vagus nerve was stimulated by electrical shock and the endogenous secretin and CCK was released by means of duodenal acidification (D. A.). The exogenous secretin, atropine and lidocaine were infused to analyse the interrelationship of neurohormones in the pancreatic exocrine secretion. The results were as follows. In chronic experiments the pancreatic secretory latency was shorter and volume larger than that in acute experiments induced by D. A. The difference is very significant (P less than 0.001). Both vagotomy and atropine significantly inhibited pancreatic secretion induced by D. A. (P less than 0.01). Lidocaine infused into duodenum inhibited pancreatic secretion induced by D. A. as well. When vagal stimulation was combined with D. A., either simultaneously or successively, the pancreatic secretion was increased more than the additive sum obtained by separate action of vagal stimulation and D. A. or secretin. In view of the above-mentioned facts, the author suggests that vagal impulses combined with D. A. or secretin act on the pancreatic exocrine secretion, and that the interaction of nerve and hormones appear to be mutually potentiated.

Stimulatory Effects of Bombesin on Plasma Trypsin Release and Exocrine Pancreatic Secretion in Dogs

We examined the effect of bombesin on plasma trypsin release and exocrine pancreatic secretion in dogs. Bombesin significantly increased plasma immunoreactive trypsin (IRT). Atropine significantly inhibited the response of plasma IRT to bombesin. Pancreatic trypsin secretion was also increased by bombesin, as well as bicarbonate and protein outputs. Atropine failed to inhibit pancreatic trypsin secretion. In conclusion, bombesin has a stimulatory effect on plasma trypsin release mediated by a cholinergic mechanism and different from pancreatic secretion.

Effects of stimulation of the hypothalamic area on pancreatic exocrine secretion in dogs

The effects of electrical or chemical (0.1 M dl-homocysteic acid) stimulation of the hypothalamus on pancreatic exocrine secretion were studied in chloralose-anesthetized and hemispherectomized dogs whose pyloric sphincter had been ligated. Excitatory pancreatic flow responses with frequently increased antral contractility and small changes in blood pressure were induced by stimulation of the ventral and dorsal portions of the anterior hypothalamic area, the lateral part of the middle hypothalamus, and the mamillary body. The inhibitory pancreatic responses with reduced antral and corpus contractility and elevated blood pressure were elicited by stimulation of the posterior hypothalamic area, the middle portion of the anterior hypothalamus and the most dorsal area of the hypothalamus. Both excitatory and inhibitory responses were obtained even in dogs with cervical cord transection. The excitatory responses and some of the inhibitory ones were abolished by vagotomy or atropine, but some inhibitory responses remained even after vagotomy. These results indicate that hypothalamic stimulation induced both excitatory and inhibitory responses in pancreatic exocrine secretion via the vagus and other routes.

Effects of amygdaloid stimulation on pancreatic exocrine secretion in dog : Naohiro Furukawa and Hiromasa Okada

Effects of amygdaloid stimulation on pancreatic exocrine secretion in dog : Naohiro Furukawa and Hiromasa Okada

Effect of Pancreatic juice and Trypsin on Oleic Acid-Stimulated Pancreatic Secretion and Plasma Secretin in Dogs

We have investigated a negative feedback mechanism in the intestinal phase of pancreatic exocrine secretion in dogs with gastric cannulas and Thomas duodenal cannulas in whom pancreatic juice was collected by cannulation of the main pancreatic duct. Intraduodenal infusion of oleic acid emulsion in a dose of 18 mmol/h resulted in a significant increase in pancreatic secretion of water, bicarbonate, and protein, which was accompanied by increased plasma concentrations of both secretin and cholecystokinin. Infusion of pancreatic juice or bovine trypsin into the duodenum significantly inhibited the oleic acid-stimulated pancreatic secretion. This inhibition coincided with a significant decrease in plasma secretin level, whereas plasma cholecystokinin concentration was not affected by either pancreatic juice or trypsin. Neither pancreatic secretion nor plasma secretin concentration was affected by intraduodenal administration of NaHCO3 solution. The trypsin-induced suppression of pancreatic secretion was prevented by intravenous administration of secretin in a dose that achieved a plasma secretin level comparable to that during the oleic acid administration. This study indicates that a negative feedback mechanism is operative in the intestinal phase of pancreatic exocrine secretion in dogs, and endogenous secretin plays a significant role in the mechanism.

Effects of DN-9693, a Synthesized Phosphodiesterase Inhibitor, on Pancreatic Exocrine Secretion in Dogs

The effects of DN-9693, a synthesized phosphodiesterase inhibitor, on the secretion of pancreatic juice were investigated in preparations of the isolated and blood-perfused dog pancreas. DN-9693 injected intraarterially caused a dose-dependent increase in the secretion of pancreatic juice and decrease in the perfusion pressure. The threshold doses to increase the pancreatic secretion and to decrease the perfusion pressure were about 100 μ and 1 μg respectively. Thus, the secretory response was less effective than the vascular response. The secretory activity of DN-9693 (0.3 mg) was approximately equal to that of 0.03 mg of 3-isobutyl-1-methylxanthine, 0.5 mg of papaverine, 5 mg of theophylline, 0.08 units of secretin and 0.2 units of cholecystokinin. The concentration of bicarbonate in the pancreatic juice induced by DN-9693 was increased, but protein concentration was not. DN-9693-induced pancreatic secretion was not modified by pretreat-ments with phentolamine, propranolol, atropine, sulpiride and cimetidine. Secretin-induced pancreatic secretion was significantly potentiated by infusion of DN-9693 (10 μg/min), but cholecystokinin-induced one was not. From these results, it is concluded that DN-9693 may produce an increase in pancreatic secretion by acting directly on the pancreatic exocrine gland of the dog, which might be mediated through an increase of intracellular cyclic AMP concentration by inhibiting phosphodiesterase activity.

Effects of DN-9693, a synthesized phosphodiesterase inhibitor, on pancreatic exocrine secretion in dogs.

The effects of DN-9693, a synthesized phosphodiesterase inhibitor, on the secretion of pancreatic juice were investigated in preparations of the isolated and blood-perfused dog pancreas. DN-9693 injected intraarterially caused a dose-dependent increase in the secretion of pancreatic juice and decrease in the perfusion pressure. The threshold doses to increase the pancreatic secretion and to decrease the perfusion pressure were about 100 micrograms and 1 microgram, to decrease the perfusion pressure were about 100 micrograms and 1 micrograms, respectively. Thus, the secretory response was less effective than the vascular response. The secretory activity of DN-9693 (0.3 mg) was approximately equal to that of 0.03 mg of 3-isobutyl-1-methylxanthine, 0.5 mg of papaverine, 5 mg of theophylline, 0.08 0.5 mg of papaverine, 5 mg of theophylline, 0.08 units of secretin and 0.2 units of cholecystokinin. The concentration of bicarbonate in the pancreatic juice induced by DN-9693 was increased, but protein concentration was not. DN-9693-induced pancreatic secretion was not modified by pretreatments with phentolamine, propranolol, atropine, sulpiride and cimetidine. Secretin-induced pancreatic secretion was significantly potentiated by infusion of DN-9693 (10 micrograms/min), but cholecystokinin-induced one was not. From these results, it is concluded that DN-9693 may produce an increase in pancreatic secretion by acting directly on the pancreatic exocrine gland of the dog, which might be mediated through an increase of intracellular cyclic AMP concentration by inhibiting phosphodiesterase activity.

Role of pancreatic polypeptide in the regulation of pancreatic exocrine secretion in dogs.

The effect of intravenous infusion of synthetic human pancreatic polypeptide (HPP) or a rabbit anti-PP serum on pancreatic exocrine secretion was studied in 10 dogs with gastric and Thomas duodenal cannulas. The infusion of HPP, at a dose of 1 microgram.kg-1.h-1, achieved a plasma PP concentration that mimicked the peak plasma concentration of PP in both interdigestive and postprandial states. This dose of HPP significantly inhibited pancreatic secretion in the interdigestive state. By contrast, immunoneutralization of circulating PP by a rabbit anti-PP serum resulted in significant increases (P less than 0.05) in both interdigestive and postprandial pancreatic secretion, including water, bicarbonate, and protein. The increase in the pancreatic secretion paralleled a decrease in circulating PP level, which lasted for as long as 5 days. Furthermore, the anti-PP serum blocked the inhibitory action of exogenous HPP on pancreatic exocrine secretion. The present study indicates that endogenous PP plays a significant role in the regulation of the pancreatic exocrine secretion in both interdigestive and digestive states. Thus we conclude that PP is another hormone regulating pancreatic exocrine secretion in dogs.

Effect of natural peptide YY on blood flow and exocrine secretion of pancreas in dogs.

Little is known regarding the mechanism by which peptide YY exerts an inhibitory effect on exocrine pancreatic secretion. The purpose of this study is to determine if peptide YY affects pancreatic blood flow with simultaneous measurement of exocrine pancreatic secretion in dogs. Pancreatic blood flow was measured by a laser Doppler flowmeter which allows continuous measurement of tissue blood flow. Natural peptide YY (0.1, 0.5, 1 microgram/kg) was infused intravenously as a bolus under background infusion of secretin (1 unit/kg/hr) in combination with cholecystokinin-octapeptide (0.1 microgram/kg/hr). Peptide YY caused a reduction of pancreatic blood flow in a dose-dependent manner as well as inhibition of pancreatic protein output, attaining the maximal reduction (28 +/- 4%) and inhibition (45 +/- 9%) at a dose of 1 microgram/kg, respectively. Simultaneous and continuous observation on tissue blood flow and exocrine secretion of the pancreas revealed that there was a highly significant correlation between the percent reduction of pancreatic blood flow and that of volume of pancreatic juice in response to peptide YY (r = 0.849, P less than 0.001). This study provides evidence that the mechanism of peptide YY-induced inhibition of exocrine pancreatic secretion is mediated, at least partly, through the decreased pancreatic blood flow.

Effects of peptide YY on dog and rat pancreatic secretion in vivo and in vitro

The action of peptide YY (PYY) on exocrine pancreatic secretion in dogs and rats was compared in in vivo and in vitro studies. PYY infused i.v. in the physiological dose range (125-1000 pmol/kg.h) reduced in a dose-dependent manner the pancreatic protein response to caerulein and suppressed basal and meat feeding or duodenal oleate-induced pancreatic secretion in conscious dogs. Both meat feeding and duodenal oleate caused significant elevation of plasma PYY levels and these showed several-fold increase during infusion of exogenous PYY (500 pmol/kg.h) inducing significant inhibition of the postprandial or oleate-stimulated pancreatic secretion. PYY in a dose range of 2.5-40 nmol/kg.h also inhibited the response to caerulein in conscious rats but failed to prevent the increment in the postprandial protein secretion in this species. PYY added in various concentrations (10(-11)-10(-6) M) to the incubation medium of the isolated dog and rat pancreatic acini failed to affect basal or caerulein- and urecholine-stimulated amylase release. This study shows that PYY is an effective inhibitor of the pancreatic secretion in vivo but not in vitro suggesting that the inhibition is mediated by an indirect mechanism.

Meal-stimulated cholecystokinin release and exocrine pancreatic secretion in dogs.

To confirm the role of cholecystokinin (CCK) and secretin in digestion, exocrine pancreatic secretion, plasma CCK, and secretin were measured simultaneously in six dogs prepared with gastric and pancreatic fistulas after feeding a solid meal. Plasma CCK concentration determined by radioimmunoassay increased significantly from the basal level, reached a peak 35 min after meal ingestion, and after a dip it further increased toward the end of the 3-h observation. Pancreatic protein output increased significantly, peaked at the fifth 10-min period, and then declined progressively. Plasma CCK concentration and pancreatic protein output correlated significantly during the first postprandial hour. Plasma secretion demonstrated significant elevation at 15 min and a peak at 25 min after a meal. Plasma secretin correlated significantly with both bicarbonate output and flow rate during the 3 h. Simultaneous measurements of plasma CCK and secretin and of pancreatic secretion suggested that postprandial pancreatic secretion is primarily mediated by releases of CCK and secretin, but these hormones do not seem to be the only factors responsible for the secretion.