cholecystokinin and Hypertrophy

Topics: Animals; Cholecystokinin; Gastrins; Gastrointestinal Hormones; Hyperplasia; Hypertrophy; Male; Pancreas; Pancreatic Juice; Rats; Rats, Inbred Strains

Topics: Cholecystokinin; Duodenal Ulcer; Duodenum; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Gastrointestinal Motility; Humans; Hydrogen-Ion Concentration; Hypertrophy; Intestinal Mucosa; Pepsin A; Secretory Rate; Vagus Nerve; Zollinger-Ellison Syndrome

Expression of cholecystokinin is found in myocardial tissues as a gastrointestinal hormone and may be involved in cardiovascular regulation. However, it is unclear whether there is an increase in cholecystokinin expression in myocardial hypertrophy progression induced by abdominal aortic constriction. The study is aimed at exploring the relationship between cholecystokinin expression and myocardial hypertrophy.. We randomly divided the 70 Sprague-Dawley rats into two groups: the sham operation group and the abdominal aortic constriction group. The hearts of rats were measured by echocardiography, and myocardial tissues and blood were collected at 4 weeks, 8 weeks, and 12 weeks after surgery. Morphological changes were assessed by microscopy. The cholecystokinin expression was evaluated by immunochemistry, Western blotting, quantitative real-time polymerase chain reaction, and enzyme-linked immunosorbent assay.. The relative protein levels of cholecystokinin were significantly increased in the abdominal aortic constriction groups compared with the corresponding sham operation groups at 8 weeks and 12 weeks. The cholecystokinin mRNA in the abdominal aortic constriction groups was significantly higher than the time-matched sham operation groups. Changes in the left ventricular wall thickness were positively correlated with the relative protein levels of cholecystokinin and the mRNA of cholecystokinin.. The development of myocardial hypertrophy can affect the cholecystokinin expression of myocardial tissues.

Topics: Animals; Cholecystokinin; Hypertrophy; Myocardium; Random Allocation; Rats; Rats, Sprague-Dawley

Megencephaly, enlarged brain, is a major sign in several human neurological diseases. The mouse model for megencephaly (mceph/mceph) has an enlarged brain, presumably due to brain cell hypertrophy, and exhibits neurological and motor disturbances with seizure-like activity, as well as disturbances in the insulin-like growth factor system. Here, we report that expression of the neuropeptides cholecystokinin, enkephalin, galanin and neuropeptide Y is dramatically changed in mceph/mceph brains compared to wild type, as revealed by in situ hybridization and immunohistochemistry. The changes were confined to discrete brain regions and occurred in a parallel fashion for peptides and their transcripts. For cholecystokinin, mceph/mceph brains had region-specific up- and down-regulations in several layers of the hippocampal formation and increased levels in, especially ventral, cortical regions. Enkephalin messenger RNA expression was up-regulated in the dentate gyrus granular layer and in ventral cortices, but down-regulated in the CA1 pyramidal layer. Enkephalin-like immunoreactivity was elevated in mossy fibers of the hippocampus and the ventral cortices. Galanin expression was increased in several layers and interneurons of the hippocampal formation, as well as in ventral cortices. Galanin-like immunoreactivity was reduced in nerve terminals in the forebrain. Neuropeptide Y expression was increased in the hippocampal formation and ventral cortices. Whether the mainly increased peptide levels contribute to the excessive growth of the brain or represent a consequence of this growth and/or of the neurological and motor disturbances remains to be elucidated.

Topics: Animals; Brain; Brain Edema; Cholecystokinin; Enkephalins; Galanin; Hypertrophy; Mice; Mice, Inbred BALB C; Mice, Transgenic; Neuropeptide Y

The influence of bile on the release of cholecystokinin (CCK) and, thereby, on the regulation of exocrine pancreatic function and growth is unsettled. The aim of this study was to elucidate the effect of long-term diversion of bile from the upper small intestine of CCK release and on the pancreas, liver, and gastrointestinal tract. A surgical biliodigestive shunt was performed in rats, diverting the bile flow directly to the middle of the small intestine. The animals were killed after 4 or 12 weeks. Plasma CCK and trophic effects on the pancreas, liver, and gastrointestinal tract were determined, as were the trypsin and chymotrypsin contents in the intestine. The CCK concentration in plasma increased 10-fold at both time points studied. The pancreas doubled its weight from 4 weeks onward. Also, pancreatic protein, DNA, and amylase contents were increased throughout the study. The liver and gastrointestinal tract were unaffected. Intraluminal bile plays a role in the feedback regulation of CCK release and is involved in this way in the control of pancreatic growth but has no similar effects on the liver or gastrointestinal tract.

Topics: Amylases; Animals; Bile; Biliary Tract Surgical Procedures; Cholecystokinin; Digestive System; DNA; Feedback; Hypertrophy; Intestine, Small; Liver; Male; Pancreas; Proteins; Rats; Rats, Sprague-Dawley

To examine the effect of gastrin on spontaneous and induced pancreatic carcinogenesis in the hamster.. Two sets of experiments were carried out, one involving long term hypergastrinaemia and one involving cancer induction during hypergastrinaemia. The effect of hypergastrinaemia accomplished by gastric fundectomy was studied for eight months. Neither fundectomised hamsters nor sham operated controls developed premalignant or malignant pancreatic lesions. In the fundectomy group, the mean pancreatic weight, total protein content, and DNA content was increased by 28%, 25%, and 25% respectively. No such increases were found in fundectomised animals receiving a cholecystokinin-B receptor antagonist during the last 24 days of the experiment. In the cancer induction study, the effect of fundectomy on N-nitrosobis(2-oxopropyl) amine induced pancreatic carcinogenesis was studied for three months. There were no significant differences in the incidence or [3H]-thymidine labelling index of focal pancreatic lesions between fundectomised and sham operated control animals.. Fundectomy with chronic hypergastrinaemia induces pancreatic hypertrophy, but does not enhance N-nitrosobis (2-oxopropyl)amine induced pancreatic carcinogenesis in the hamster. The increases in growth were inhibited by a cholecystokinin-B receptor antagonist, indicating that the trophic effect of fundectomy is mediated by gastrin.

Topics: Animals; Benzodiazepinones; Carcinogens; Cholecystokinin; Cricetinae; Disease Models, Animal; Gastric Fundus; Gastrins; Hypertrophy; Male; Mesocricetus; Neoplasms, Experimental; Nitrosamines; Pancreas; Pancreatic Neoplasms; Phenylurea Compounds; Receptors, Cholecystokinin

A8947 is a member of the sulfonyl urea class of compounds and is the active ingredient in a commercial broad leaf herbicide. This compound has been shown to produce pancreatic hypertrophy in rats, mice, and dogs. The objectives of this study were to investigate the mechanism(s) for the A8947 induction of pancreatic acinar cell hypertrophy and proliferation and to evaluate whether these pancreatic changes are reversible. A8947 was fed to male Crl:CD BR rats for up to 28 days (0, 300, 10,000, 30,000 ppm) or 56 days (0, 30,000 ppm). Rats were terminated on Test Days 7, 14, and 28 to assess the time course and dose response for the A8947-induced pancreatic changes, while rats terminated on Test Day 56 were used to assesss the reversibility of the pancreas effects at 30,000 ppm A8947. A8947 produced significant increases in pancreatic weight and acinar cell proliferation and diffuse acinar cell hypertrophy in 7 days at 10,000 and 30,000 ppm dose levels. By Day 14, absolute pancreas weights in the 10,000 and 30,000 ppm groups were maximally increased and remained at these levels throughout the study. In contrast, acinar cell proliferation in the 30,000 ppm group was still elevated at Test Day 14, but attenuated relative to the 7-day response, and returned to control levels by Test Day 28. No effects were observed at 300 ppm after a 28-day exposure period, while complete reversibility of A8947-induced pancreatic effects was demonstrated at 30,000 ppm following a 1-month recovery period (Test Day 56). Cholecystokinin (CCK) levels were increased by A8947 and closely followed the time course for pancreatic changes. MK-329, a specific CCKA receptor antagonist, completely ablated the ability of 30,000 ppm A8947 to increase pancreas weight following 7 days of exposure. A8947 did not bind the CCKA receptor in a receptor competition assay, negating any potential agonist mechanism. A8947 did, however, inhibit trypsin in vitro, suggesting a mechanism of action similar to that of raw soy protein, in which trypsin inhibition in vivo results in increased CCK levels followed by pancreatic acinar cell hypertrophy and proliferation.

Topics: Animals; Benzodiazepinones; Cholecystokinin; Devazepide; Dose-Response Relationship, Drug; Herbicides; Hypertrophy; Male; Pancreas; Pyrimidines; Rats; Receptor, Cholecystokinin A; Receptors, Cholecystokinin; Trypsin Inhibitors

The time course of recovery from hypertrophied pancreas to the normal size was examined and compared with the time course of normal size pancreas getting hypertrophied in rats. The bile-pancreatic duct was cannulated and bile-pancreatic juice was partly bypassed the proximal intestine. Trypsin and bile salts disappeared from the lumen of proximal quarter of intestine during the first 7 postoperative days; however, these appeared again after the 14th postoperative day and luminal trypsin activity reached 3 to 4 times the control level during the postoperative days 14-56. Conversely, the plasma cholecystokinin (CCK) concentration significantly increased on day 7, then declined thereafter, and the mRNA level of CCK in the proximal intestinal mucosa increased and reached the maximal level on day 7. Pancreatic wet weight, as an index of size, was significantly increased and remained high on postoperative days 7-28, then returned to the control size on day 56. Therefore, it took 7 d for the pancreas to become hypertrophied by high circulating CCK, however the pancreatic size recovered to the normal size on the 56th postoperative day although the plasma CCK level decreased with the appearance of luminal bile salt and trypsin during postoperative days 14-56. In conclusion, it took longer for the hypertrophied pancreas to return to the normal size (14 or more d) than for the normal size pancreas to become hypertrophied (7d).

Topics: Animals; Base Sequence; Bile; Bile Acids and Salts; Cholecystokinin; Hypertrophy; Intestinal Mucosa; Kinetics; Male; Molecular Sequence Data; Organ Size; Pancreas; Pancreatic Juice; Radioimmunoassay; Rats; Rats, Wistar; RNA, Messenger; Somatostatin; Trypsin

Topics: Animals; Cholecystokinin; Esters; Ethanol; Gabexate; Guanidines; Hypertrophy; Male; Pancreas; Rats; Rats, Wistar

When pancreaticobiliary diversion (PBD) surgery was performed in rats, plasma CCK level increased, the pancreas grew mainly by proliferation, and pancreatic trypsinogen showed a remarkable increase, although amylase and lipase synthesis were somewhat decreased. The sensitivity of amylase release against CCK-8 in the pancreatic acini decreased when plasma CCK level was high. These changes in pancreatic growth and pancreatic enzyme secretion caused by PBD were completely inhibited by the CCK-receptor antagonist loxiglumide. From these results, intrinsic CCK was considered to play an important role in both pancreatic enzyme synthesis and proliferation.

Topics: Amylases; Animals; Biliary Tract Surgical Procedures; Cholecystokinin; Hypertrophy; Lipase; Male; Pancreas; Proglumide; Rats; Rats, Wistar; Secretin; Time Factors; Trypsinogen

The effect of gastric fundectomy with hypergastrinaemia on the pancreas in rats was studied for 14 months. Rats with hypercholecystokininaemia that had had a pancreaticobiliary diversion (PBD) operation and sham operated rats served as controls. Fundectomised rats showed a significant increase in pancreatic weight and total DNA and protein content compared with sham operated rats. DNA flow cytometry showed a significantly higher ratio of tetraploid to diploid nuclei in pancreatic tissue after fundectomy than after sham operation. Mean values of all these variables were significantly lower after fundectomy than after PBD. Acidophilic atypical acinar cell foci of the pancreas were diagnosed in both fundectomised and PBD operated rats, but not in sham operated controls. The volume density and 3H-thymidine labelling index of the acidophilic atypical acinar cell foci were significantly lower after fundectomy than after PBD. Changes consistent with pancreatic adenoma were diagnosed in the PBD group only. In conclusion, fundectomy lasting about half of the life span in rats causes pancreatic hyperplasia and hypertrophy, as well as development of acidophilic atypical acinar cell foci. Although hypergastrinaemia is a prominent feature, it may not be the only factor responsible for this pancreaticotrophical effect of fundectomy.

Topics: Animals; Autoradiography; Body Weight; Cholecystokinin; DNA; Gastric Fundus; Gastrins; Hypertrophy; Male; Organ Size; Pancreas; Ploidies; Rats; Rats, Wistar; Time Factors

The role of exogenous and endogenous cholecystokinin has been studied in the process of pancreatic regeneration after acute pancreatitis. A mild form of pancreatitis was induced in rats by subcutaneous cerulein at 12 micrograms.kg-1, three times a day for 2 days. After 3 days of rest, the cerulein-treated rats were divided into four groups: rats with acute pancreatitis fed 20% casein, who received no treatment; rats fed 50% casein; rats fed 20% casein supplemented with 1% soybean trypsin inhibitor (SBTI); and rats fed 20% casein who received 1 microgram.kg-1 of subcutaneous cerulein, three times a day. Controls were fed 20% casein plus saline subcutaneously. Rats were killed after 5, 10, or 20 days of treatment. Pancreatitis resulted in significant decreases in pancreatic weight and contents of protein, amylase, chymotrypsin, RNA and DNA. During the regenerative process, 1 microgram.kg-1 of cerulein increased all parameters to control values within 5 days and induced pancreatic growth thereafter. SBTI restored the pancreas to normal after 10 days with cellular hypertrophy; the 50% casein diet gave a response similar to SBTI without hypertrophy. It can be concluded that cerulein and SBTI can accelerate pancreatic regeneration after an attack of acute pancreatitis.

Topics: Acute Disease; Amylases; Animals; Body Weight; Ceruletide; Cholecystokinin; Chymotrypsin; Drug Therapy, Combination; Glycine max; Hypertrophy; Male; Nucleic Acids; Organ Size; Pancreas; Pancreatitis; Proteins; Rats; Rats, Inbred Strains; Regeneration; Trypsin Inhibitors

1 Raw soya flour (RSF) in the diet induces pancreatic hypertrophy and hyperplasia in the rat, changes ascribed to production of a high circulating level of cholecystokinin (CCK) due to inhibition of trypsin in the duodenum. Prolonged ingestion results in pancreatic adenomas and carcinomas. 2 L-364, 718, a potent, highly specific CCK antagonist was used to investigate the short-term role of CCK. 3 In rats fed 50% RSF and L-364, 718 5 mg kg-1 p.o. twice daily for 4 d, there was inhibition of pancreatic hypertrophy and hyperplasia, which is further evidence that peripherally-acting CCK plays a major role in the generation of RSF-mediated changes in the pancreas.

Topics: Animals; Benzodiazepinones; Cholecystokinin; Devazepide; Glycine max; Hyperplasia; Hypertrophy; Male; Mitosis; Organ Size; Pancreas; Rats; Rats, Inbred Strains; Receptors, Cholecystokinin

This study was an investigation of the role of cholecystokinin (CCK) in the stimulatory action of cholestyramine on rat exocrine pancreas. Postprandial CCK release was significantly enhanced by acute administration of cholestyramine (12.7 +/- 1.8 vs 3.7 +/- 0.5 pmol/L in controls). Over four weeks, rats were fed either regular diet or diet containing 6% cholestyramine, and were treated with the specific CCK receptor antagonist L-364,718 (2 x 0.5 mg/kg body weight/day s.c.) or DMSO (vehicle for the antagonist). Cholestyramine significantly increased pancreatic weight and trypsin and chymotrypsin contents. L-364,718 abolished these effects. Concomitant administration of antagonist and cholestyramine elevated amylase content, compared to controls. CCK levels in fasted animals did not differ between the four groups. The effect of the same dose of L-364,718 on pancreatic enzyme depletion, induced by the protease inhibitor camostate, was studied in a control experiment. A single dose of camostate (200 mg/kg) caused a 44-68% decrease in enzyme content. L-364,718 reversed this effect for all enzymes. We conclude that CCK is the mediator of cholestyramine-induced pancreatic hypertrophy and increase in content of proteases. After long-term administration, the CCK receptor antagonist, in combination with cholestyramine revealed an agonistic effect on individual, pancreatic enzyme content.

Topics: Administration, Oral; Animals; Benzodiazepinones; Cholecystokinin; Cholestyramine Resin; Chymotrypsin; Devazepide; Dimethyl Sulfoxide; DNA; Dose-Response Relationship, Drug; Esters; Gabexate; Guanidines; Hypertrophy; Male; Organ Size; Pancreas; Rats; Rats, Inbred Strains; Receptors, Cholecystokinin; Time Factors; Trypsin; Trypsin Inhibitors

A single dose of the synthetic proteinase inhibitor, Camostat (FOY-305; 100 mg/kg), was administered orally to rats. Pancreata were isolated and then perfused to examine the change in the level of resting fluid secretion. As early as 6 h after administration of the single dose of Camostat, the resting fluid secretion was significantly elevated. Twelve hours after administration, resting fluid secretion was maximally elevated, whereas contents of trypsinogen, chymotrypsinogen, and amylase per DNA in the pancreas were significantly decreased. After 12 h, the level of resting fluid secretion gradually decreased to the control resting level in contrast to significant increases in contents of the pancreatic enzyme and zymogens, and wet weight in acinar cells. We further examined the mechanism mediating the elevated resting fluid secretion. Our results are compatible with the view that the elevation of resting fluid secretion may be maintained by spontaneous activation of ion transporters: an ouabain-sensitive Na-K ATPase, an amiloride-sensitive Na-H antiporter, and a unique Cl transporter that is insensitive to furosemide, bumetanide, SITS, and DNDS.

Topics: Administration, Oral; Animals; Biological Transport; Cholecystokinin; Electrolytes; Esters; Gabexate; Guanidines; Hypertrophy; Male; Pancreas; Pancreatic Juice; Protease Inhibitors; Rats; Rats, Inbred Strains

Pancreaticobiliary diversion (PBD) caused a more than twofold increase in pancreatic weight after 10 days, with no further increase after 15 or 20 days or 7 weeks. Although the weight gain after PBD to a minor extent (10%) reflected increased water content, the main cause was hypertrophy and hyperplasia with increased pancreatic protein and DNA content. The cholecystokinin (CCK) concentrations in plasma were increased 10-fold from the 5th postoperative day. The trophic effects on the pancreas were completely abolished by the CCK antagonist L-364,718. Further, the antagonist caused a significant reduction in pancreatic weight, protein, and DNA in otherwise untreated controls. We conclude that PBD in rats induces trophic effects on the pancreas by increasing circulating CCK concentrations and that CCK is important for normal pancreatic growth.

Topics: Anastomosis, Surgical; Animals; Benzodiazepinones; Cholecystokinin; Devazepide; Hyperplasia; Hypertrophy; Ileum; Male; Organ Size; Pancreas; Rats; Rats, Inbred Strains

Since endogenous cholecystokinin (CCK) is released after oral administration of camostate, it has been suggested that camostate-induced pancreatic growth is mediated via circulating CCK. To test this concept, we investigated the effects of three potentially inhibitory substances on rat pancreatic hypertrophy caused by feeding of camostate over 2 weeks: (1) L-364,718, the novel specific highly potent nonpeptide CCK receptor antagonist, (2) octreotide (SMS 201-995), a potent long-lasting somatostatin analogue and (3) pancreastatin (33-49), the biologically active C-terminal fragment of the novel gastrointestinal peptide pancreastatin. Camostate feeding (200 mg/kg) once daily for 14 days induced a significant increase in pancreatic weight, total protein, trypsinogen and polyamine levels, whereas total amylase content was substantially diminished. Simultaneous oral or subcutaneous treatment with L-364,718 (0.3 mg/kg twice daily) completely suppressed all trophic effects of camostate. Octreotide (25 micrograms/kg twice daily s.c.) and pancreastatin (33-49) (10 micrograms/kg twice daily s.c.) did not change any trophic parameter. In case of octreotide it could be shown that two daily injections only partially suppressed elevated CCK levels. Pancreatic DNA and putrescine levels were slightly reduced in rats receiving the CCK antagonist alone. These results demonstrate that camostate-induced pancreatic hypertrophy in rats is caused by the release of endogenous CCK which may contribute to the maintenance of normal pancreatic DNA and putrescine concentrations.

Topics: Animals; Benzodiazepinones; Cholecystokinin; Chromogranin A; Devazepide; Esters; Gabexate; Guanidines; Hypertrophy; Male; Octreotide; Pancreas; Pancreatic Hormones; Protease Inhibitors; Rats; Rats, Inbred Strains

Repeated intragastric instillation of a trypsin inhibitor (camostate) to rats resulted in pancreatic growth. This was ascribed to the trophic effect of endogenously released cholecystokinin (CCK). We evaluated the CCK-releasing potency of different doses of camostate (50-400 mg/kg body weight administered perorally) during the course of experimentally induced pancreatic growth. Significant increments of pancreatic weight and protein and trypsin content of the pancreata were observed after 5 days of camostate treatment; changes were further pronounced after 10 days. Juice flow and protein and trypsin output from the hypertrophied pancreata were enhanced after 5 days. These effects were diminished after 10 days of camostate treatment. The direct increase in plasma CCK in response to camostate after pretreatments by daily oral doses of 200 mg/kg camostate over 5 or 10 days was more pronounced in rats with pancreatic hypertrophy compared with untreated controls. These findings mirror possible adaptation of CCK-releasing cells to "desensitisation" of acinar cells after pancreatic hypertrophy.

Topics: Animals; Cholecystokinin; Dose-Response Relationship, Drug; Esters; Female; Gabexate; Guanidines; Hypertrophy; Pancreas; Protease Inhibitors; Rats; Rats, Inbred Strains

Chronic feeding of rats with camostate results in pancreatic hypertrophy or hyperplasia, or both. Previous studies suggest that this effect of camostate occurs via an increase in endogenous cholecystokinin due to an enteral feedback mechanism involving the inhibition of trypsin in the duodenum. Studies employing proglumide, a weak and relatively nonspecific cholecystokinin antagonist, have failed to fully abolish camostate-induced pancreas growth. We examined the effects of L-364,718, a new and highly potent cholecystokinin receptor antagonist, on camostate-induced pancreas growth in rats. The pancreas weights and the concentrations of ribonucleic acid, protein, and chymotrypsinogen in the pancreas of rats treated with camostate alone were significantly elevated over those of controls. These effects of camostate were completely abolished in rats treated with camostate + L-364,718. The pancreas weights and the concentrations of deoxyribonucleic acid and ribonucleic acid in the pancreas of rats treated with L-364,718 alone were significantly lower than values in control rats. These data indicate that camostate-induced pancreas growth in rats appears to be dependent on the actions of endogenous cholecystokinin and that cholecystokinin may play a role in the maintenance of pancreatic growth in normal rats.

Topics: Animals; Benzodiazepinones; Cholecystokinin; Devazepide; Esters; Gabexate; Guanidines; Hypertrophy; Male; Organ Size; Pancreas; Protease Inhibitors; Rats; Rats, Inbred Strains

Chronic diversion of pancreatic and biliary secretions away from the proximal small intestine results in pancreatic hypertrophy in adult rats. Serum levels of cholecystokinin (CCK) were measured in age-matched control and surgically diverted rats at various times after operation by a radioimmunoassay method that was specific for the sulfated form of CCK. The concentration of CCK was markedly increased in bypassed rats as compared with controls. The increases in circulating CCK in bypassed rats was substantiated by a bioassay method that measured physiologically active CCK. The degree of pancreatic hypertrophy and the increase in CCK levels both progressed with time up to 23 days after surgery. Linear regression analysis showed an apparent direct correlation between pancreatic weights and serum CCK levels (r = 0.99). Feeding bypassed rats with diets containing various pancreatic and biliary supplements did not abolish the hyperplastic response of their pancreata. However, feeding with diets supplemented with bile partially suppressed the increase in serum CCK levels, while a diet containing Cotazyme and bile completely suppressed this increase. The discrepancy between serum CCK levels and the degree of pancreatic hypertrophy in the supplemented bypassed rats was further demonstrated by the lack of correlation using linear regression analysis (r = 0.33). The observed pancreatic hypertrophy in the absence of high serum levels of CCK in the bypassed rats fed bile and Cotazyme supplements suggests that serum hypertrophic factors other than CCK may also be involved in the enteral feedback regulation of pancreatic growth.

Topics: Animals; Cholecystokinin; Duodenum; Feedback; Hypertrophy; Pancreas; Rats; Rats, Inbred Strains

Topics: Animals; Caseins; Cholecystokinin; Dietary Proteins; Hypertrophy; Intestine, Small; Male; Pancreas; Pancreatic Juice; Rats; Rats, Inbred Strains; Trypsin; Trypsin Inhibitors

The interrelationship between trypsin/trypsinogen and enterokinase (EK) was studied in rats following induction of trypsinogen hypersecretion by various agents. Both soybean trypsin inhibitor and para-aminobenzamidine increased intraluminal tryptic activities to a level about twice that found in the control rats. This resulted in an increase in the mucosal and the intraluminal contents of EK in the rat small intestine. On the other hand, in cholecystokinin-treated rats, although there was an increase of intraluminal trypsin, the increase was about 80% less than in the inhibitor-fed rats. Under this condition, there was no effect on the mucosal or the intraluminal EK. These results suggested that substantial increase in intraluminal trypsin/trypsinogen levels (two-fold over control) will increase the mucosal and the intraluminal concentrations of EK in the rat small intestine. Our observation extends previous reports that a decreased level of trypsin/trypsinogen, such as in pancreatic insufficiency, leads to a decrease in mucosal EK. These observations, when taken together, strongly support the modulating role of intraluminal trypsin/trypsinogen levels in controlling the EK concentrations in the small intestine.

Topics: 4-Aminobenzoic Acid; Animals; Cholecystokinin; Endopeptidases; Enteropeptidase; Enzyme Induction; Hypertrophy; Intestine, Small; Male; Pancreas; Rats; Rats, Inbred Strains; Time Factors; Trypsin Inhibitors; Trypsinogen; Weaning

We studied the effect of raw soya flour (RSF) given as a single gavage or for long-term periods on pancreatic blood flow. These effects were compared with the response to treatment with cholecystokinin (CCK) since it has been suggested that RSF feeding releases CCK. In acute experiments total pancreatic blood flow was significantly increased after infusion of CCK (60 Ivy dog units X kg-1 X h-1) and after gavage with preparations of RSF or heated soya flour (HSF). When expressed as flow per 100 g pancreatic weight, the greatest increase was seen after gavage with RSF. In separate chronic studies, total pancreatic blood flow was significantly increased in rats fed RSF for 4 wk compared with rats fed HSF, but because of pancreatic enlargement in rats fed RSF flow per 100 g pancreatic weight was similar in the two groups. When rats fed RSF for 4 wk were changed to standard rat cubes for 48 h before study, pancreatic blood flow (ml/min and ml X min-1 X 100 g pancreas-1) and total pancreatic DNA decreased significantly compared with rats fed RSF continuously. However, when CCK was infused intravenously during the 48-h period on cubes, pancreatic blood flow and DNA remained significantly increased and were not significantly different from values in rats fed RSF continuously. These results show that the effects of RSF feeding and CCK treatment on pancreatic growth and blood flow are similar and are consistent with the postulated role of CCK as the trophic hormone released by RSF feeding.

Topics: Animals; Cholecystokinin; Flour; Glycine max; Hypertrophy; Male; Microspheres; Organ Size; Pancreas; Rats; Rats, Inbred Strains; Regional Blood Flow

A dose of FOY-305 [N,N-dimethylcarbamoylmethyl-4-(4-guanidinobenzoyloxy)phenylacetate methanesulfonate; 100 mg/kg body weight] was administered orally once a day for 30 days to a group of rats (FOY group). To the control group of rats, 10 ml/kg body weight of distilled water (a solvent of FOY-305) was administered in the same way. The FOY-305 administration induced hypertrophy of the pancreas: the increase in wet weight of the pancreas was significantly higher than the increase in DNA content. The administration also induced hyperpyknia in the FOY group as shown by the increased concentration of constituents (amylase, trypsinogen, and chymotrypsinogen) in the pancreas. The secretory responses of the exocrine pancreas to stimulation with cholecystokinin (CCK) were examined in vivo. The secretory responses induced by lowered doses of CCK in the FOY group were slightly greater than those in the control group, but the differences were not statistically significant. On the other hand, the responses induced by higher doses of CCK were significantly greater than those in the control group. The secretory responses to stimulation with CCK or acetylcholine (ACh) were examined further in vitro using an isolated perfused pancreas. Protein output induced by lower doses of the secretagogues (146-730 pM CCK or 10 nM ACh) was similar in the control and the FOY groups, but the output induced by higher doses of the secretagogues (1,460 pM CCK or 30-100 nM ACh) in the FOY group was significantly larger than that in the control group. The present results provided evidence that the FOY-305-induced hypertrophy and hyperpyknia of the rat pancreas coincided with potentiation of secretory responses to higher doses of the secretagogues.

Topics: Acetylcholine; Administration, Oral; Animals; Cholecystokinin; Esters; Gabexate; Guanidines; Hypertrophy; In Vitro Techniques; Male; Pancreas; Protease Inhibitors; Rats; Rats, Inbred Strains

Topics: Animals; Ceruletide; Cholecystokinin; Hypertrophy; Insulin; Islets of Langerhans; Male; Pancreas; Rats; Trypsin Inhibitors

Topics: Aging; Amylases; Animals; Body Weight; Cholecystokinin; Chymotrypsin; DNA; Hyperplasia; Hypertrophy; Lipase; Organ Size; Pancreas; Proteins; Rats; RNA; Stimulation, Chemical

Topics: Adult; Biliary Tract Diseases; Cholecystography; Cholecystokinin; Cystic Duct; Drainage; Female; Gallbladder; Humans; Hypertrophy; Male; Methods; Pressure

Topics: Adult; Cholecystography; Cholecystokinin; Cystic Duct; Female; Gallbladder Diseases; Humans; Hypertrophy; Male; Middle Aged