Secretion Of Pancreatic Juice Research Articles

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.

The preparation of biotinyl-ε-aminocaproylated forms of the vasoactive intestinal polypeptide (VIP) as probes for the VIP receptor

Vasoactive intestinal polypeptide (VIP) was biotinyl-ε-aminocaproylated using sulfosuccinimidyl-β-(biotinamido) hexanoate thereby producing a series of products that were separated by high performance liquid chromatography (HPLC). Seven VIP-derivatives were isolated and the number and location of biotinyl-ε-aminocaproylation was determined by a combination of enzymatic degradation and plasma desorption mass spectrometry (PDMS). Receptor binding experiments with the VIP biotinyl-ε-aminocaproylated derivatives revealed IC 10 values for the monobiotinyl-ε-aminocaproylated peptides that were 1.3–3.2 times higher than for natural VIP. All isolated biotinyl-ε-aminocaproylated derivatives possess VIP-like bioactivity as shown by an assay measuring pancreatic juice secretion in cat, VIP biotinyl-ε-aminocaproylated in position lysine 15 being almost equipotent with natural VIP.

The Acute Pancreatotoxic Effects of the Plant Nitrile 1-Cyano-2-hydroxy-3-butene

The effects of synthetic 1-cyano-2-hydroxy-3-butene (CHB), a racemic mixture of the (R)- and (S)-enantiomers, were studied in adult male rats. The compound given by gavage in olive oil at doses of 25-200 mg/kg causes toxic effects on the pancreas that resemble those seen when naturally occurring CHB is given to rats. At 6 h after dosing, pancreatic edema is seen with doses of 100 mg/kg and greater. The edema fluid had a high protein content, indicating a marked increase in macromolecular permeability of the pancreatic microcirculation. A loss of zymogen granules from the acinar cells and a lacy supranuclear vacuolation of the acinar cell cytoplasm was observed. At 4 h after dosing, pancreatic nonprotein thiols were depleted and rebounded at 24 h to three times control values. At 120 h nonprotein thiol levels decreased but were still elevated compared with control values. Glutathione-S-transferase activity in the pancreas had a similar pattern of change with initial reduction, followed by elevation at 24 h. In rats with pancreatic and biliary fistulas, intraduodenal CHB caused a transient early stimulation of pancreatic juice secretion followed by a return to control values in the case of the lower doses of CHB and depression of flows at larger doses. All doses of CHB caused a dose-related depression of protein concentration in pancreatic juice. Pancreatic juice flow was almost abolished at doses of 200 mg/kg. CHB caused a dose-dependent choleresis accompanied by a marked reduction in bile acid concentrations in bile.(ABSTRACT TRUNCATED AT 250 WORDS)

Early acinar cell changes in caerulein-induced interstitial acute pancreatitis in the rat

Early ultrastructural and immunohistochemical changes caused by supramaximal secretory stimulation with caerulein were studied in the rat pancreas. The morphological basis for the earlier reported decrease of pancreatic juice secretion after supramaximal caerulein was the appearance of swollen and irregular zymogen-like material containing structures with short segments of budding bristle-coated membranes in the apical parts of acinar cells. Images of exocytosis of zymogen granules were only few. Later, marked vacuolization and signs of autophagocytosis are seen in the basal cytoplasm. Immunohistochemistry showed that the large zymogen containing structures were intensively labelled for trypsin at the early stages of the experiment (4-30 min). Later (1-2 h), the vacuoles were empty or contained occasional, small-labelled granules only. The pancreozymin-receptor antagonist proglumide as well as cycloleucine that inhibits protein synthesis by inhibiting the synthesis of S-adenosylmethionine, effectively prevented the caerulein induced acinar cell changes. The irregular zymogen containing structures with coated pits on their surface indicate disturbed zymogen granule formation leading to the accumulation of large lakes of zymogen material and finally to marked autophagocytosis in acinar cells. The effects of caerulein are receptor-mediated and depend on the process of methylation in the formation of zymogen granules.

Origin and Characterization of Immunoreactive Somatostatin in Rat Pure Pancreatic Juice

This study was undertaken to determine the origin and forms of immunoreactive somatostatin (SLI) present in the pancreatic juice of cannulated nonanesthetized rats. The systemic origin of somatostatin (SS) was assessed from bolus intravenous injections of either I125-Tyr1-SS-14 or synthetic SS-14 under basal and stimulated pancreatic juice secretion, and from measurements of radioactivity and SS-14 in the collected juice. Gel filtration of pooled juice samples indicated that there were no forms of SS corresponding to standards of I125-Tyr1-SS-14 or SS-14, but radioactive material eluted in the area of either I125-Tyr or free iodine. Investigation of the presence of SS-14 in the juice by radioimmunoassay (RIA) led to the identification of a 23-kDa SS-like immunoreactive protein that did not correspond to any of the three known forms of SS present in the pancreatic tissue (Pro-SS, SS-28, and SS-14). By boiling the juice before the RIA, this 23-kDa protein was no longer detectable by RIA. These data suggest that this protein may be a "putative" enzyme, degrading the SS tracer in the RIA. This possibility is supported by the observation that boiled juice lost this capacity of interfering with the RIA. In conclusion, SS in the pancreatic juice, if present, is not from systemic origin and the juice contains an active thermosensitive substance degrading the SS tracer in the RIA.

Development of Exocrine Pancreas Function in Chronically Cannulated Pigs During 1–13 Weeks of Postnatal Life

The development of exocrine pancreas function was studied in Swedish Landrace pigs surgically fitted with a chronic pancreatic duct catheter and a duodenal re‐entrant cannula. The juice secretion and output of total protein and trypsin activity were followed before (basal secretion) and after feeding (postprandial secretion) during the first 1–13 weeks of life. The results showed that throughout the suckling period, up to 4–5 weeks of age, the basal pancreas function remained low and the secretory response to feeding, i.e., nursing sow milk, was also low. After weaning, the pancreatic juice secretion as well as the output of protein and trypsin activity markedly increased with respect to both basal and postprandial levels. Furthermore, the enzyme composition of the pancreatic juice changed qualitatively during this period. During the first 2 weeks of life, the intravenous administration of cholecystokinin (CCK) and secretin did not stimulate exocrine function, but a significant effect was achieved from 3–4 weeks of age. These results showed that there was both an increase in exocrine pancreas function and a qualitative change in the hydrolytic enzyme pattern during porcine postnatal ontogeny, apparently correlated with the changes in diet around weaning. An increase in the response of the pancreas to hormonal stimulation was also observed during the suckling period.

Development of Exocrine Pancreas Function in Chronically Cannulated Pigs During 1–13 Weeks of Postnatal Life

The development of exocrine pancreas function was studied in Swedish Landrace pigs surgically fitted with a chronic pancreatic duct catheter and a duodenal re-entrant cannula. The juice secretion and output of total protein and trypsin activity were followed before (basal secretion) and after feeding (postprandial secretion) during the first 1-13 weeks of life. The results showed that throughout the suckling period, up to 4-5 weeks of age, the basal pancreas function remained low and the secretory response to feeding, i.e., nursing sow milk, was also low. After weaning, the pancreatic juice secretion as well as the output of protein and trypsin activity markedly increased with respect to both basal and postprandial levels. Furthermore, the enzyme composition of the pancreatic juice changed qualitatively during this period. During the first 2 weeks of life, the intravenous administration of cholecystokinin (CCK) and secretin did not stimulate exocrine function, but a significant effect was achieved from 3-4 weeks of age. These results showed that there was both an increase in exocrine pancreas function and a qualitative change in the hydrolytic enzyme pattern during porcine postnatal ontogeny, apparently correlated with the changes in diet around weaning. An increase in the response of the pancreas to hormonal stimulation was also observed during the suckling period.

Effects of phorbol esters and secretin on pancreatic juice secretion in the anaesthetized rat

1. An investigation was made of the effects of phorbol esters, 12- O-tetradeconylphorbol acetate (TPA) and secretin on pancreatic juice secretion in the anaesthetized rat. TPA (10 −12–10 −8 mol/kg body wt) evoked marked dose-dependent increases in secretory rate and total protein output. 2. An inactive phorbol ester (4α-phorbol-12–13-didecanoate; 4αPDD) had no effect on the secretory rate but increased total protein output compared to saline control animals. 3. When TPA was administered in combination with the protein kinase C inhibitor, Polymyxin B (10 −8 mol/kg body wt) both secretory rate and protein output were significantly reduced ( P < 0.001) compared to TPA alone. 4. Secretin (50–1600 pmol/kg body wt) increased both pancreatic juice flow and total protein output in a dose-dependent manner. 5. Simultaneous administration of secretin (50–1600 pmol/kg body wt) and TPA (10 −10 mol/kg body wt) resulted in a marked attenuation in the secretin-induced secretory rate while secretin-evoked protein output was unaffected. 6. The results indicate that protein kinase C activation is associated with pancreatic juice secretion and it may also modulate secretin-induced pancreatic juice flow in the anaesthetized rat.

Digestion of soybean meal and canola meal protein and amino acids in the digestive tract of young ruminants.

Eight male Holstein calves (body weight 68 +/- 5 kg; age 75 +/- 6 d), each with a permanent re-entrant pancreatic cannula and T-type ileal and duodenal cannulas, were used in a crossover design with four animals per group to determine amino acid kinetics and digestibilities in the digestive tract of calves fed soybean meal (SBM) and canola meal (CM) protein. The SBM and CM diets were fed twice daily at a level of 900 g at each feeding time (air-dry basis). With the exception of methionine, crude protein and amino acid flows at the proximal duodenum, expressed as a percentage of intake, were not influenced by dietary protein source. Apparent ileal and total tract digestibilities of CP and amino acids were reduced (P less than .05) by feeding CM compared to SBM, but apparent ileal digestibility of methionine was not affected by dietary protein source. Except for methionine, net disappearance of all amino acids in the small intestine, relative to the amount fed, was higher for the SBM diet than for the CM diet. Net disappearance or synthesis of amino acids in the large intestine were not affected by dietary protein source. Similarly, dietary protein source did not affect (P greater than .05) the secretion of pancreatic juice or concentrations of protein, chymotrypsin and trypsin in pancreatic juice. Soybean meal protein has higher ileal and total gastrointestinal tract digestibility than CM protein for young, growing calves.

Protein digestion in mink

The aim of the study was to investigate amino acid composition and digestion during passage through the digestive tract of adult mink, using chromic oxide as an indigestible indicator. Whole fish and fish meal were applied as dietary protein sources. The animals were sacrificed 1 1/2 or 3 hours after a test meal. The average length of the digestive tract was 4.13 times the body length. The feed passage rate averaged about 3 1/2 hours. Analyses of digesta from stomach, three sections of small intestine and colon/rectum revealed certain changes compared with dietary values, mainly due to dilution with endogenous protein. Generally, the contents of methionine, lysine and arginine declined, while those of cystine and threonine increased. The digestibilities of amino acids were slightly positive in the stomach, but negative in the first section of the small intestine, reflecting the secretion of pancreatic juice. Towards the second and third section of small intestine and colon/rectum, the digestibilities increased rapidly. Compared with whole fish, fish meal proteins were less efficiently digested. It is indicated that the fecal digestibility method overestimates the amounts of absorbed amino acids

Effects of pirenzepine on CCK-stimulated canine pancreatic exocrine secretion

1. 1. The effects of the anticholinergic compound pirenzepine on pancreatic secretion stimulated by intravenous infusions of increasing doses of CCK (0.025-0.4 Ivy Dog Unit/kg/min) were investigated in fasting anaesthetized dogs. 2. 2. Pirenzepine (0.75 mg/kg i.v.) slightly reduced the increases in the pancreatic juice secretion evoked by CCK. 3. 3. Similar results were obtained with others anticholinergic compounds as atropine (3 mg/kg i.v.) and hexametonium (5 mg/kg i.v.).

Effect of L-364,718 on GRP-stimulated pancreatic and gastric secretions and GI peptides in conscious dogs.

The effect of L-364,718, a cholecystokinin (CCK) receptor antagonist, on exocrine pancreatic secretion, gastric secretion, and plasma levels of gastrointestinal (GI) peptides stimulated by gastrin-releasing peptide (GRP) was examined in five conscious dogs. Intravenous infusion of graded doses of synthetic porcine GRP (18, 36, and 178 pmol/kg/h) caused significant and dose-dependent increases in pancreatic and gastric juice secretion and in plasma levels of pancreatic polypeptide (PP), CCK, and gastrin. Intravenous injection of L-364,718 (20 nmol/kg) significantly inhibited GRP-stimulated pancreatic outputs of juice volume, protein, and amylase and plasma PP release. L-364,718, however, did not affect gastric juice volume and plasma levels of CCK and gastrin. The results suggest that endogenously released CCK is, at least in part, responsible for GRP-stimulated pancreatic protein and enzyme secretions and PP release in dogs. The results further suggest that GRP-stimulated pancreatic secretion might be, in part, a direct response of GRP to exocrine pancreas.

Allopurinol Stimulates Pancreatic Exocrine Secretion in the Dog

The effects of allopurinol on the secretion of pancreatic juice were investigated both in live animals and in preparations of isolated, blood-perfused dog pancreas and were compared with those of secretin. An i.v. administration of allopurinol (3-10 mg/kg) caused a dose-dependent increase in the pancreatic secretion. The secretory responses to 3 and 10 mg/kg of allopurinol were approximately equal to those to 0.03 and 0.1 U/kg of secretin, respectively. An intra-arterial (i.a.) infusion of allopurinol (0.5-1.2 mg/min) also elicited dose-dependent increases in flow rates, bicarbonate concentrations, and outputs of pancreatic exocrine secretion, but protein concentrations were little affected by allopurinol. Similar results were obtained in the juice induced by an i.a. infusion of secretin (0.012-0.05 U/min). Both bicarbonate and protein concentrations in the juice obtained with allopurinol were almost the same as those obtained with secretin at a similar flow rate of pancreatic secretion. The secretory activities at 0.5, 1.0, and 1.2 mg/min of i.a. allopurinol infusion corresponded roughly to those at 0.012, 0.025, and 0.05 U/min of i.a. secretin infusion, respectively. Therefore, the secretory action of allopurinol was similar to that of secretin. The allopurinol-induced secretion was not modified by pretreatment with atropine sulfate, cimetidine, or sulpiride hydrochloride. These results suggest that allopurinol stimulates pancreatic secretion by acting directly on ductular cells of the dog pancreas.

INHIBITORY EFFECT OF OUABAIN AND ACETAZOLAMIDE ON SECRETIN‐STIMULATED PANCREATIC EXOCRINE SECRETION IN ANAESTHETIZED DOG

1. The effects of ouabain and acetazolamide on the secretion of pancreatic juice stimulated by secretin in anaesthetized dogs were investigated. 2. Intra-arterial injection of ouabain (1-10 micrograms) and acetazolamide (1-10 mg) caused dose-dependent decreases in the volume of pancreatic juice. When both drugs were added together, the inhibitory effects were significantly higher than for each drug alone. 3. The bicarbonate concentration in the pancreatic juice was decreased and the chloride concentration was increased by ouabain and acetazolamide, but sodium and protein concentrations were not modified. 4. The results suggest that the Na+,K+-ATPase and carbonic anhydrase activities play important roles in water and electrolyte secretion, and that ouabain and acetazolamide inhibit secretin-stimulated pancreatic secretion by acting on different systems in the exocrine cells in dogs.

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.

Substitution of milk protein with isolated soy protein in calf milk replacers.

The influence of replacement of milk protein by isolated soy protein on digestion and pancreatic enzyme secretion was determined in nine Holstein male calves. Calves (average weight 47 kg) were fitted with permanent re-entrant pancreatic and a T-type cannula in the distal ileum at 6 to 10 d of age. Following a 2-wk recuperation period, the calves were fed three milk replacers in a triplicated 3 x 3 latin square. Experimental diets consisted of a control, in which 100% of the CP originated from spray-dried skim milk powder (SM), and the test diets, in which 50% (SM/ISP) or 100% (ISP) of the skim milk protein was replaced by isolated soy protein. Each experimental period lasted 2 wk. Replacement of SM protein by ISP decreased (P less than .05) the digestibilities of protein and most amino acids. Ileal digestibilities of total indispensable amino acids for SM, SM/ISP and ISP diets were 82.1, 75.8 and 61.8%, respectively, and total tract digestibilities of total indispensable amino acids were 90.0, 82.6 and 74.0%, respectively. Including ISP did not affect (P greater than .05) the volume of secretion of pancreatic juice, protein or chymotrypsin; however, the secretion of trypsin decreased (P less than .05). Reduction in trypsin secretion may be responsible, in part, for the lower amino acid digestibilities in milk replacers containing isolated soy protein.

Effect of short-chain fatty acids on pancreatic exocrine secretion in calves aged 2 weeks and 13 weeks.

Effects of short-chain fatty acids on pancreatic exocrine secretion were studied under anesthesia in calves within 2 weeks of age (2-wks calves) given only whole milk and milk replacement and in which rumen fermentation has not begun yet, and in calves at 13 weeks of age (13-wks calves) weaned at 40 days of age and in which rumen fermentation has already begun. Basal rate of juice flow and protein concentration and amylase activity in pancreatic juice under basal condition were significantly lower in the 2-wks calves than those in the 13-wks calves. Intravenous administrations of acetate, propionate and butyrate stimulated pancreatic juice secretion and protein and amylase output in both groups of calves. Those responses were increased with increasing carbon number in the molecule of fatty acids. Although the response of amylase output (/kg of body weight) in the 2-wks calves was significantly less than that in the 13-wks calves, the response of juice flow and protein output (/kg of body weight) in the 2-wks calves were equivalent to or greater than those in the 13-wks calves. These results indicate that the characteristic of pancreas, being stimulated by short-chain fatty acids, in calves and probably in other ruminants is not generated on the process of postnatal development, but has been already acquired before rumen fermentation begins.

Effect of glucagon-(1–21)-peptide on secretin-stimulated pancreatic exocrine secretion in anesthetized dogs

The effects of glucagon-(1–21)-peptide on pancreatic exocrine secretion and plasma glucose levels were studied and compared with those of native glucagon in anesthetized dogs. Intravenous bolus administration of 1 nmol or 10 nmol/kg of glucagon-(1–21)-peptide evoked a significant inhibition of secretin-stimulated pancreatic juice secretion and protein output in a dose-dependent manner, as equimolar doses of glucagon did. Native glucagon induced an immediate and transient increase in pancreatic juice volume, which was followed by a significant inhibition. However, glucagon-(1–21)-peptide showed only the inhibitory action. Glucagon-(1–21)-peptide had no effect on plasma glucose levels even when a dose of 10 nmol/kg was given. The results suggest that the N-terminal amino-acid residues of glucagon play an important role in the inhibition of pancreatic e exocrine secretion.

Isolation and characterization of a variant form of vasoactive intestinal polypeptide

A variant form of the vasoactive intestinal polypeptide (VIP) has been isolated. It was found to consist of a molecule which instead of the C-terminal asparagine amide of VIP has a C-terminal extension of Gly-Lys-Arg. This VIP variant displaces VIP in a VIP receptor assay, reacts with N-terminally-directed antisera in a VIP radioimmunoassay and possesses VIP-like bioactivity in an assay measuring pancreatic juice secretion in the cat.