Pancreatic Enzyme Content Research Articles

Serum pancreatic enzymes in HIV-seropositive patients

Serum concentrations of trypsin and elastase I were determined in 109 HIV Ab-positive patients (52 asymptomatic HIV-infected patients, 25 with lymphadenopathy syndrome, and 32 with acquired immunodeficiency syndrome) to assess the prevalence of possible pancreatic damage in these patients. Serum trypsin was abnormally elevated in 46 of the 109 patients (42.2%): 19 of the 52 asymptomatic HIV-infected patients (36.6%), 9 of the 25 with lymphadenopathy syndrome (36%), and 18 of the 32 with acquired immunodeficiency syndrome (56.3%). Serum elastase 1 was elevated in 14 of the 109 HIV Ab-positive patients (12.8%): 3 of the 52 asymptomatic HIV-infected patients (5.8%), 3 of the 25 with lymphadenopathy syndrome (12%), and 8 of the 32 with acquired immunodeficiency syndrome (25%). None of the patients with abnormally high serum pancreatic enzyme concentrations had clinically evident pancreatic disease. There was no statistically significant difference in serum levels of trypsin and elastase I between drug addicts and nonaddicts, between alcoholics and nonalcoholics, or between those with cytomegalovirus infection and those without. A significant inverse relationship was found between serum enzyme concentrations and the number of CD4+ lymphocytes. The results of this study show that high levels of serum trypsin and elastase are present in an elevated percentage of patients with acquired immunodeficiency syndrome, suggesting that the pancreas is frequently damaged in this disease. The finding of abnormally high serum enzyme concentrations not only in patients with AIDS, but also in asymptomatic carriers and in patients with lymphadenopathy syndrome suggests an association between HIV infection and the development of pancreatic lesions.

Responses of the Exocrine Pancreatic Secretion to Spontaneous Feeding in Rats with Bile-Pancreatic Juice Diversion

The regulatory response of the exocrine pancreas was examined in rats under unanesthetized and unrestrained conditions. The previous study demonstrated that the pancreatic protease secretion increased 2-fold after spontaneous feeding of a low protein diet in chronically bile-pancreatic cannulated rats (normal rats) whose bile-pancreatic juice (BPJ) was returned to the duodenum. In the present study, we observed the response of the exocrine pancreatic secretion to spontaneous feeding of a low protein diet in rats with chronic diversion of BPJ from the proximal small intestine for 6 days (bypass rat) whose diverted BPJ was returned to the upper ileum. During BPJ diversion, the dry weight and the protein content of the pancreas were increased 2-fold, compared with normal rats. Also, the levels of trypsinogen and chymotrypsinogen in the pancreas were increased several times, but amylase was decreased. The basal secretion of enzymes after a 24-hr fast was enhanced in bypass rats in proportion to the pancreatic enzyme contents. After spontaneous feeding of 8% casein fat-free diet, the increases in the pancreatic secretion of bypass rats were much smaller than those of normal rats. In contrast, the increase of BPJ flow of bypass rats after feeding was greater than that of normal rats. These findings represent that the chronic diversion of BPJ exerts hypergrowth of pancreas and hypersecretion of proteases in the fasting state, and less sensitivity of pancreatic enzyme secretion to dietary feeding.

Role of Cholecystokinin in Cholestyramine-induced Changes of the Exocrine Pancreas

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.

Increased lysophosphatidylcholine and pancreatic enzyme content in bile of patients with anomalous pancreaticobiliary ductal junction

Increased lysophosphatidylcholine and pancreatic enzyme content in bile of patients with anomalous pancreaticobiliary ductal junction

Increased lysophosphatidylcholine and pancreatic enzyme content in bile of patients with anomalous pancreaticobiliary ductal junction

A high incidence of inflammation and carcinoma of the biliary tract in patients with anomalous pancreaticobiliary ductal junction has been well documented. The change in biliary phospholipids as a result of the reflux of pancreatic juice into the biliary tract through anomalous pancreaticobiliary ductal junction may be responsible for it. We developed a new method of analysis of phospholipid classes using aminopropyl Bond Elut cartridge for extraction and high-performance liquid chromatography for separation. Satisfactory recovery was achieved (i.e., more than 95% for both phosphatidylcholine and lysophosphatidylcholine). With this method, the bile of 11 patients with anomalous pancreaticobiliary ductal junction was examined. The concentration and proportion of lysophosphatidylcholine in bile were much higher in the presence of anomalous pancreaticobiliary ductal junction than in controls (3.44 +/- 1.50 mmol/L vs. 0.52 +/- 0.25 mmol/L, 60.0% +/- 31.0% vs. 2.3% +/- 1.4% in gallbladder bile; p less than 0.001). In contrast, the concentration of phosphatidylcholine and the sum of phosphatidylcholine and lysophosphatidylcholine in gallbladder bile significantly decreased (p less than 0.001), but in hepatic bile they did not. An inverse correlation was found between the proportion of lysophosphatidylcholine and phospholipid concentration in gallbladder bile. Phospholipase A2 and amylase activities in bile were markedly high. Increased total fatty acid concentration and proportion of unsaturated fatty acid in bile were found. Total bile acid concentration in gallbladder bile was significantly lower than in controls. These results suggest that a considerable amount of lysophosphatidylcholine, which is known to have a cytotoxic effect, isp reduced by phospholipase A2 in refluxing pancreatic juice, and an increased concentration of lysophosphatidylcholine gives rise to cell damage causing mucosal hyperplasia and metaplasia.(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation of Rat Pancreatic Nuclear Triiodothyronine Receptor by Glucocorticoid

The nuclear T3 receptors in rat pancreas exhibit a characteristic maturation pattern during development and are subjected to autologous regulation by thyroid hormones. To see if glucocorticoids also regulate T3 receptors in the pancreas, rats at various age groups were subjected to experimental conditions that altered their glucocorticoid status and the corresponding changes in nuclear T3 receptors, and exocrine enzymes in their pancreata were evaluated. Hydrocortisone administration to normal suckling and weaning rats did not change total T3 binding capacity or the dissociation constant as measured at 30 degrees C (Kd30). A significant increase in the degree of occupancy of the T3 receptor was found at 5-10 days after treatment with hydrocortisone (42.2 + 4.1% vs. 19.2 + 2.0%). T3 binding capacity and exocrine enzyme concentrations were significantly reduced in both adrenalectomized (Adx) pups and adults, indicating a continuous dependency on glucocorticoid from preweaning to adulthood. In adrenalectomized rat pups, either T4 or glucocorticoid replacement alone restored T3 binding capacity and exocrine enzyme concentrations. T4 and glucocorticoid were given together to Adx rats, the level of stimulation of both pancreatic T3 binding capacity and exocrine enzyme concentrations was found to be equal to the sum of the stimulation by each of these hormones when given alone. Furthermore, a good correlation was found between Bmax30 (Bmax measured at 30 degrees C, representing total sites) for T3 binding and exocrine enzyme activities in different groups following various experimental treatments. These findings provide further evidence that thyroxine can act directly on the rat pancreas presumably through the T3 receptor in regulating the postnatal development of the exocrine enzymes.

How to protect human pancreatic enzyme activities in frozen duodenal juice

We determined whether activity of pancreatic enzymes could be maintained in frozen duodenal juice by diluting the specimens or by adding nutrients or a chymotrypsin inhibitor. Human duodenal juice was obtained during cholecystokinin octapeptide IV administration. Trypsin, chymotrypsin, lipolytic, lipase, and colipase activities were measured in fresh undiluted or diluted (1:4 and 1:16 with saline and T-tube bile) duodenal juice as well as after adding CaCl2, casein, triolein, or a chymotrypsin inhibitor. Subsequently, the samples were frozen at −20 °C, and enzyme activities were measured at 1, 2, 3, 7, 14, 28, and 56 days. Activities of chymotrypsin and colipase did not change during freezer storage. Trypsin survival was variable in juice from different subjects. By contrast, in duodenal juice to which no nutrient or only CaCl2 had been added, 90%, 65%, and 40% (P = 0.05 vs. undiluted) of lipolytic activity was lost by 56 days in undiluted and 1:4 or 1:16 diluted duodenal juice samples, respectively. The loss of lipolytic activity was prevented (P < 0.05) by adding casein or casein and triolein to undiluted and 1:4 diluted samples and turkey egg white to undiluted samples. The loss of lipolytic activity was strongly associated with loss of lipase activity (r = 0.97) but only weakly associated with loss of colipase activity (r = 0.49). In summary, chymotrypsin and colipase are well preserved in frozen duodenal juice and can be used to accurately assess concentrations of pancreatic enzymes after thawing frozen duodenal samples. If it is necessary to measure lipolytic activity after freezing samples, lipase can be maintained by adding casein or a chymotrypsin inhibitor to juice before freezing.

Dose-dependent effect of chronic CR 1409 administration on rat exocrine pancreas in normal rats and following subtotal gastrectomy

Billroth II subtotal gastrectomy (B II) in rats results in pancreatic hyperplasia and hypertrophy, and affects pancreatic enzyme composition. A postulated mechanism for this effect is an increased postprandial release of endogenous CCK. In the present study, the influence of chronic administration of the CCK receptor antagonist CR 1409 was tested in B II and control rats. Forty male Wistar rats underwent B II subtotal gastrectomy and were divided into three groups. Group A: 20 rats with a standard diet; group B: 10 rats with low dose CR 1409 (0.3 mg/kg bw/d) in the diet; group C: 10 rats with high dose CR 1409 (3.0 mg/kg bw/d). Each rat of groups B and C was pair-fed with one animal of group A. Further, 40 control rats with no operation served as controls, and were, similarly to the B II rats, divided into three groups. After 28 d, the animals were sacrificed; wet wt, DNA-, protein-, amylase-, trypsin, and lipase content and concentration of the pancreas were determined. Basal CCK plasma levels were measured at the day of pancreatic explantation. Low dose CR 1409 induced an increase of pancreatic wet wt by 28%, and of DNA content by 26% in B II rats. High dose CR 1409 had no effect. Both doses of CR 1409 had similar effects on pancreatic enzyme concentrations (U/mg DNA); amylase increased by 50% in group B, and by 86% in group C, trypsin by 35% in group B, and by 41 % in group C; lipase was unchanged. In control rats, low dose CR 1409 induced pancreatic growth (wet wt + 27%; DNA content +24%) and enzyme adaptation (amylase +96%, trypsin +54%). High dose CR 1409 had no effect. Basal CCK plasma levels after an overnight fast were unaltered in all groups. In summary, low dose CR 1409 promotes pancreatic growth and affects enzyme composition in control rats. In B II rats, the trophic pancreatic response is further increased by low dose CR 1409. High dose CR 1409 had no effect in both experimental groups.

Effects of TRH on Pancreatic Growth and Secretion in Rats

Thyrotropin-releasing hormone (TRH) has been shown to be scattered throughout the gastrointestinal tract. High concentrations of TRH are reported in the pancreas of animals and humans. The present study was designed to investigate the pattern of pancreatic adaptation following chronic TRH administration in rats. Ten male Wistar rats were injected daily at 8.00 and 16.00 h with TRH (total dose of 6 mg/kg of body weight/day) via a chronic gastric fistula. Ten pair-fed control animals were injected with a saline solution. After 10 days, the rats were killed after an overnight fast; pancreatic wet weight, DNA, protein, amylase, trypsin, and lipase content were determined. Blood TRH levels were measured using a specific RIA (TRH antiserum K2B7, normal range of 30-80 fmol/ml). TRH increased pancreatic wet weight (+70%, p less than 0.01), DNA content (+83%, p less than 0.01), and protein content (+42%, p less than 0.05). Pancreatic enzyme concentrations (U/mg of DNA) were decreased (amylase, -81%; trypsin, -47%; lipase, -59%, p less than 0.01). Absolute rates of amylase discharge (U/mg of DNA) in vitro were reduced in TRH-treated rats (p less than 0.01) but the relative amount of basal and stimulated amylase discharge (% of total) was not influenced by TRH. Blood TRH levels were significantly increased (324 +/- 53 vs. 48 +/- 6 fmol/ml, p less than 0.01) 12 h after the last TRH administration. These data indicate that chronic TRH administration in rats induces pancreatic hyperplasia but decreases the pancreatic concentration of digestive enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)

Exocrine pancreatic function in children and adolescents with insulin-dependent diabetes mellitus

Exocrine pancreatic function was evaluated in 21 diabetic children on the basis of a p-aminobenzoic acid (PABA) test and a determination of fasting serum amylase, pancreatic isoamylase, lipase, trypsin and elastase levels. Fecal chymotrypsin was also measured. Compared to the controls, the diabetic children had significantly lower levels of trypsin ( P < 0.001) and elastase ( P < 0.02). Fecal chymotrypsin appeared to be significantly lower ( P < 0.01) in diabetic children than in controls but in all patients fecal chymotrypsin values registered above the limit considered to be normal. No significant correlation was observed between pancreatic enzyme concentrations, serum and urinary PABA values, and chronologic age, HbA 1 and insulin requirement. Only for serum PABA a significant negative correlation with duration of disease ( P < 0.01) has been observed. These data show that exocrine pancreatic function may be abnormal in children with IDDM.

Does Acute Consumption of Large Alcohol Amounts Lead to Pancreatic Injury? A Prospective Study of Serum Pancreatic Enzymes in 300 Drunken Drivers

Blood samples of 300 consecutive subjects suspected for drunken driving were prospectively analyzed for concentrations of pancreatic and hepatic enzymes. Mean alcohol concentration was 1.5 +/- 0.8 0/00 (+/- SD; range 0-3.7 0/00). Increased enzyme concentrations were found in 25/300 subjects for amylase, in 43/300 for trypsin, in 49/300 for gamma-glutamyl transferase and in 82/300 for glutamic oxaloacetic transaminase. Subjects with alcohol concentrations greater than 1 0/00 had abnormal pancreatic and hepatic enzymes more frequently than subjects with alcohol concentrations smaller than 1 0/00. However, pancreatic enzyme levels were higher than twice the upper normal limit only in 3/300 subjects, whereas hepatic enzyme levels exceeded twice the upper normal limit in 31/300 subjects. Therefore, other factors in addition to alcohol are necessary to initiate acute pancreatitis. The liver is more susceptible to acute injury by alcohol than the pancreas.

Aging impairs pancreatic response to refeeding following a protein-free diet.

Changes in content and recovery of pancreatic enzymes after a protein-free diet were examined in young (8-month) and old (26-month) Fischer-344 female rats. In control rats fed a normal diet for 15 days, no significant difference between young and old rats was observed in pancreatic weight or in pancreatic content of protein, enzymes, and DNA. A 7-day protein-free diet significantly decreased pancreatic wet weight as well as content of protein, chymotrypsin, amylase, and DNA in both age groups, whereas body weight and amount of daily food intake did not differ from respective control values (in normal diet-fed rats) in either age group. In young rats, chymotrypsin and protein contents were significantly greater than control values during the recovery period in which rats were fed a normal diet following the 7-day protein-free treatment. In contrast, these values in old rats remained lower than corresponding control values throughout the entire recovery period. These results agree with our previous study suggesting that aging probably attenuates the reserve capacity of the pancreas for enzyme secretion, but not its basal functions.

Epidermal Growth Factor Inhibits Rat Pancreatic Cell Proliferation, Causes Acinar Cell Hypertrophy, and Prevents Caerulein-Induced Desensitization of Amylase Release*

The in vivo effects of epidermal growth factor (EGF) on pancreatic growth and digestive enzyme concentrations were compared with the actions of the pancreatic secretagogue caerulein in the adult rat. EGF (10 micrograms/kg BW) did not alter pancreatic weight or protein content. However, this concentration of EGF inhibited [3H]thymidine incorporation into DNA by 44%, decreased DNA content by 20%, and increased the concentrations of amylase, chymotrypsinogen, and protein by 106%, 232%, and 42%, respectively. Pancreatic acini prepared from EGF-treated rats exhibited a characteristic secretory response to caerulein that was superimposable to that obtained in acini from saline-treated rats. In both groups of acini half-maximal and maximal stimulation of amylase release occurred at approximately 5 pM and 50 pM caerulein, respectively. In contrast to EGF, caerulein (1 microgram/kg BW) increased pancreatic weight by 29% and protein content by 59%, and enhanced [3H]thymidine incorporation into DNA by 70%. Although caerulein increased the concentrations of pancreatic amylase and chymotrypsinogen by 38% and 297%, respectively, pancreatic acini prepared from caerulein-treated rats were less sensitive to the actions of caerulein in vitro when compared with acini from control rats. Indeed, the EC50 was shift from 4.8 pM to 9.8 pM after 4 days of treatment. EGF potentiated the actions of caerulein on pancreatic weight, protein content, and chymotrypsinogen concentration, and prevented the caerulein-induced alteration in the secretory responsiveness of the acinar cell. Conversely, caerulein reversed the inhibitory effect of EGF on thymidine incorporation. These findings suggest that EGF may modulate the trophic effects of certain gastrointestinal hormones, and may participate in the regulation of pancreatic exocrine function in vivo.

Effect of atropine on feedback regulation of pancreatic secretion in rats

In the present study the effect of atropine on feedback regulation of pancreatic function was investigated in male rats. Orogastric tube feeding of a single dose of the protease inhibitor camostate (100 mg) caused a 6-fold increase in plasma CCK. This was accompanied by a 50% decrease in pancreatic enzyme content for up to 6 h. The effect of i.v. infusion of atropine (100 micrograms.kg-1.h-1) was studied 60 and 180 min after camostate feeding. Atropine completely abolished the decrease in enzyme content 180 min after camostate feeding. The stimulated CCK plasma levels were significantly lowered by the infusion of atropine 60 min, but not 180 min, after feeding of camostate. It is discussed that a cholinergic pathway mediates CCK release in the early phase of feedback regulation of pancreatic function.

Alcohol-induced chronic pancreatitis in rats after temporary occlusion of biliopancreatic ducts with Ethibloc.

Chronic obstructive pancreatitis-like histological and biochemical alterations were provoked in male Wistar rats with Ethibloc occlusion of the common bile duct and the main pancreatic ducts. After the disappearance of the glue from the ducts, a gradual and almost total recovery was demonstrated during a 2-month observation period. About 12 g/kg of alcohol (20% vol/vol) given daily by gastric intubation and ad libitum intake inhibited the recovery of pancreatic weight and enzyme contents in the occluded rats, and within a 2-month period chronic calcifying-type pancreatitis became evident with some signs of remaining obstructive pancreatitis-like lesions. Cessation of alcohol administration after 2 months resulted in a recovery of pancreatic weight and enzyme contents, although morphological regeneration was less pronounced and calcification remained visible in some rats. A 50% raw soy flour diet provoked some further changes in the proportion of enzymes without any supplementary increases of pancreatic weight and protein content. This animal model of chronic pancreatitis demonstrates that chronic obstructive and calcifying pancreatitis can appear together and earlier if the etiological factors act in combination. Suppression of pancreatic regeneration by alcohol seems to be necessary to maintain chronic pancreatitis-like lesions and to develop calcification.

Effect of a new potent CCK antagonist, lorglumide, on caerulein‐ and bombesin‐induced pancreatic secretion and growth in the rat

1. The effect of lorglumide, a new potent cholecystokinin (CCK) antagonist, on pancreatic secretion and growth induced by caerulein and bombesin was studied in the rat. 2. Pancreatic exocrine secretion was studied both in vitro (isolated and perfused pancreatic segments) and in vivo (anaesthetized animals with cannulation of the common bile duct) whereas the trophic effect was investigated after short-term (5 days) administration of the peptides and/or lorglumide. 3. Both caerulein and bombesin stimulated amylase release from in vitro pancreatic segments in a concentration-dependent manner. Although the efficacy of both peptides was virtually identical, the potency of caerulein was higher than that of bombesin. Lorglumide displaced the concentration-response curves to caerulein to the right without affecting the maximum response, suggesting a competitive antagonism. The Schild plot analysis of data gave a straight line with a slope not significantly different from unity. The calculated pA2 for lorglumide was 7.31 +/- 0.45. The antagonist, however, was completely ineffective when tested against bombesin-induced amylase release. 4. In vivo experiments confirmed results from in vitro studies since lorglumide (5 and 10 mg kg-1) significantly reduced pancreatic exocrine secretion induced by caerulein without affecting the response to bombesin. 5. Administration of either peptide increased the weight of the pancreas, the total pancreatic protein and DNA, trypsin and amylase content. Lorglumide (10 mg kg-1), administered together with caerulein, reduced the peptide-induced increase in pancreatic weight, protein and enzyme content. On the contrary, when lorglumide was given together with bombesin, all the parameters that were examined were not altered by concomitant administration of the antagonist. 6. These results have demonstrated the ability of lorglumide to antagonize the effects on the pancreas of a CCK-analogue, caerulein, and its inability to affect bombesin-induced pancreatic secretion and growth, suggesting that lorglumide is a potent and selective antagonist of CCK-receptors in the pancreas.

Evidence for a direct trophic effect of bombesin on the mouse pancreas: in vivo and cell culture studies

The present work studied the effect of chronic bombesin on the mouse pancreas and analyzed whether or not this effect was direct. Bombesin administered s.c. 3 times daily for 4 days at various concentrations (0.1, 1, 10, 20 μg/kg b. wt.) induced pancreatic growth in a dose-dependent manner. This growth was characterized by an increase in pancreatic weight, its protein and RNA contents suggesting cellular hypertrophy. Pancreatic enzyme content was also increased, especially for amylase (14-fold) and at a lesser degree for chymotrypsin and lipase (2.5-fold). The DNA content of the gland increased significantly after a 1 μg/kg bombesin treatment suggesting hyperplasia. [ 3H]thymidine incorporation into DNA increased slightly from 24 h after the first bombesin injection and more obviously at 72 and 96 h indicating DNA synthesis. To determine the direct effect of bombesin on pancreatic acinar cell growth cells were cultured as monolayers on collagen gels in media lacking added hormones and containing 2.5% FBS with or without bombesin (1 μM–1 nM) or caerulein (10 nM). [ 3H]thymidine incorporation into DNA was increased by caerulein (10 nM) and bombesin (100 nM and 1 μM). Therefore, it is concluded that bombesin is a pancreaticotrophic peptide in mice. Moreover, it is suggested that this effect occurs directly on pancreatic cells.

Raised serum concentrations of pancreatic enzymes in smokers.

Raised serum concentrations of pancreatic enzymes in smokers.

Secretagogue-Induced Enzyme Release from the Exocrine Pancreas of Rats Following Adaptation to a High Protein Diet

The mechanisms of pancreatic adaptation to dietary changes and whether these changes are reflected in the serum are not fully understood. The present study investigates secretagogue-induced release of digestive enzymes from dispersed pancreatic acini as well as the concentrations of these enzymes in serum and pancreas after adaptation to a high protein diet. Adult rats were fed an 8.5% casein diet ad libitum. After 14 d the rats were divided into three groups and fed isoenergetic diets constituting 8.5, 24 or 40% protein for an additional 6 d. No significant differences in final body weight or pancreatic weight were observed among the groups of rats. Rats adapted to the 40% protein diet showed significantly higher trypsin and chymotrypsin activity in pancreatic homogenates than rats fed the 8.5% protein diet. These changes in pancreatic enzyme content were not reflected in serum. Pancreatic acini isolated from the 8.5% protein group showed a markedly reduced responsiveness to cholecystokinin (CCK-8), secretin- and carbachol-induced enzyme release in comparison to the other two dietary groups, although basal enzyme release was the same in all groups. These results indicate that the secretion of pancreatic enzymes following a physiological stimulus is affected by a low protein, high carbohydrate diet.

Different effects of intraperitoneal or subcutaneous administration of H2-antagonists on pancreatic response to chronic administration of caerulein in rats.

This study deals with the effect of H2-receptor antagonists on pancreatic response to chronic administration of caerulein. Caerulein was administered alone or combined with cimetidine, ranitidine or famotidine twice a day in various regimes. At the end of treatment, pure pancreatic juice was collected after hormonal stimulation. Then, the rats were killed, and growth and composition of the pancreatic tissue were determined. Caerulein increased pancreatic weight and enzyme content as well as volume and enzyme activity of pancreatic juice. When given alone the three H2-receptor antagonists were totally ineffective. Both ranitidine and famotidine, but not cimetidine, significantly reduced pancreatic response to chronic administration of caerulein only when given intraperitoneally together with caerulein. On the contrary, separate applications of caerulein and ranitidine (or famotidine) did not influence caerulein-stimulated pancreatic growth or enzyme secretion. Moreover, in rats treated both intraperitoneally and subcutaneously with caerulein, the H2-antagonists reduced the pancreatic response only partially and in proportion to the intraperitoneal dose of caerulein. The responsiveness of pancreatic tissue to subcutaneous caerulein was not modified. The results suggest that H2-receptor antagonists induce (1) impaired uptake of caerulein when given together with peptide, but (2) have no specific inhibitory effect on pancreatic response to caerulein.