Pancreatic DNA Research Articles

New model of acute necrotizing pancreatitis induced by excessive doses of arginine in rats

We examined the biological and histologic characteristics of a new experimental model of acute necrotizing pancreatitis induced by excessive doses of arginine in rats. Rats were given a single intraperitoneal injection of 500 mg/100 g body weight of L-arginine. At 12-24 hr after the arginine injection, serum levels of amylase, lipase, and anionic trypsin(ogen) reached respective peak values 2, 5, and 20 times those of control rats without arginine and returned to control levels after 24-48 hr. The contents of pancreatic protein, DNA, and digestive enzymes were markedly reduced after the arginine injection and reached their nadirs at 72 hr. After 14 days these levels were almost normal. Histologic examination revealed a number of small vesicles within acinar cells at 6 hr, which were identified as markedly swollen mitochondria by the electron microscope. Other intracellular organelles and nuclei also showed degenerative changes. At 12 hr interstitial edema appeared, and acinar cell necrosis was seen after 24 hr. The extent and severity of necrotic changes of pancreatic exocrine tissue with inflammatory cell infiltration were maximal at 72 hr. At seven days, pancreatic acinar cells began to regenerate, and pancreatic architecture appeared almost normal after 14 days. The present study has demonstrated that the administration of excessive doses of arginine induces a new, noninvasive experimental model of acute necrotizing pancreatitis.

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)

Cholecystokinin Is Responsible for Growth of the Pancreas after Pancreaticobiliary Diversion in Rats

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.

Stimulation by colostrum or mature milk of gastrointestinal tissue development in newborn pigs.

Porcine colostrum and milk were orally administered to newborn pigs to evaluate their gastrointestinal growth-promoting activity. Five piglets per treatment group were gavage-fed 5% lactose (L), defatted colostrum (C) or defatted mature milk (d 16 of lactation) (M) at 3-h intervals over a 24-h period. Colostrum and milk were administered on equivalent dry matter basis and all piglets received 1 mCi of [3H]thymidine per kg BW at the onset of feeding. Small intestines of C- and M-fed pigs were 1.6-and 1.3-fold, respectively, the weight of small intestines of those fed L (P less than .01). Total DNA content of intact small intestines were not different among groups; however, cpm [3H]thymidine/mg intestinal DNA of C and M piglets exceeded (P less than .05) that for L piglets. DNA content and cpm [3H]thymidine of intestinal mucosa did not differ among groups. Total protein in the intestines and intestinal mucosa of C pigs exceeded (P less than .01) that for L and M pigs. Total RNA in the small intestine and intestinal mucosa were similar for C and M groups but less (P less than .01) for L piglets. Stomach and pancreas weights among all pigs were similar, although C and M pigs exceeded L pigs in stomach (P less than .01) and pancreas (P less than .01) RNA content. In contrast, no differences in stomach DNA, protein and cpm [3H]thymidine or in pancreatic DNA, protein and cpm [3H]thymidine were detected. SDS-polyacrylamide gel electrophoresis was used to identify qualitative and quantitative differences in the protein compositions of porcine colostrum and mature milk.(ABSTRACT TRUNCATED AT 250 WORDS)

Thyroidal Regulation of Rat Pancreatic Nuclear Triiodothyronine Receptor during Postnatal Development

We have shown previously that the rat pancreas contains nuclear T3 receptors which exhibit a characteristic maturation pattern during development. To investigate whether these receptors are subjected to autologous regulation by thyroid hormones, the effect of T4 on the binding capacity (Bmax), dissociation constant (Kd), and receptor occupancy were followed in intact rat pups at various ages. Hyperthyroidism (by daily injection of T4 0.1 micrograms/g body wt to intact pups starting 4 days before death at 5, 10, 15, and 20 days of age) increased while hypothyroidism (by propylthiouracil feeding) decreased the total T3 binding capacity during preweaning ages (mean maximal binding capacities as estimated by Scatchard analysis, at 30 C for 14-20 days old eu-, hyper-, and hypothyroid pups: 186, 229, and 129 fmol/mg non-histone protein (NHP). The thyroid conditions also affected the percentage of T3 receptor occupancy but not the affinity of binding (as measured by Kd). Concomitantly, these conditions also caused corresponding changes in pancreatic weights, DNA and protein contents, and the concentrations of amylase, trypsinogen, and lipase. The postnatal developmental retardation induced by 6-n-propyl-2-thiouracil treatment was reversed by T4 replacement. The results suggest that rat pancreatic T3 nuclear receptors during postnatal ages are modulated by T4, and such modulation apparently in turn affects the development of the exocrine enzymes.

Effects of Long-Term CCK Stimulation and CCK Blockade on Pancreatic and Intestinal Growth, Morphology, and Function

This study evaluated the effects of long-term cholecystokinin (CCK) stimulation and blockade on pancreatic and intestinal growth, function, and morphology. CCK release was induced by feeding of the protease inhibitor camostate and CCK blockade by feeding of the CCK antagonist CR 1409. Four groups of NMRI-mice received the following diets for 9 months (each group consisting of 36 mice): (1) chow (control); (2) chow + 100 mg/kg/day camostate; (3) chow + 50 mg/kg/day CR 1409; (4) chow + 100 mg/kg/day camostate + 50 mg/kg/day CR 1409. Long-term feeding of camostate greatly increased pancreatic weight by induction of marked hypertrophy (increase in protein content) and moderate hyperplasia (increase in DNA content). Camostate feeding also increased secretory capacity of the exocrine pancreas. Despite camostate-induced growth neither hyperplastic nor neoplastic nodules developed. The CCK-antagonist CR 1409 markedly inhibited the effects of camostate which are therefore mainly mediated by CCK. Neither long-term CCK stimulation nor CCK blockade altered morphology or composition of duodenal mucosa. Feeding of CR 1409 alone (i.e., without camostate) slightly but significantly decreased pancreatic content of protein and secretory capacity of enzymes when compared to the chow-fed control; pancreatic weight and DNA content remained unchanged after long-term administration of CR 1409. Thus, long-term, continuous and effective blockade of the CCK-receptor only slightly inhibited pancreatic growth and secretory capacity. CCK is, therefore, not an essential growth factor for the pancreas, although increases of endogenous CCK stimulate pancreatic growth and secretory capacity.

Proliferative Response of Different Exocrine Pancreatic Cell Types to Hormonal Stimuli

The trophic effect on the exocrine pancreas of the cholecystokinin analogue cerulein was studied in a long-term experiment (20 or 160 micrograms/kg/24 h for 14 days) in mice by measuring changes in pancreatic weight and protein, amylase, and DNA content. Further, the selective cell growth stimulation exerted by various doses of cerulein (4, 20, 54, 160 micrograms/kg/24 h) on different exocrine pancreatic cell types was studied by continuous administration of 3H-thymidine. In the first experiment animals given 20 micrograms/kg/24 h of cerulein had increased pancreatic weight and amylase and protein content, whereas the animals given the higher dose had unchanged weight and a less pronounced increase in amylase and protein content. The pancreatic DNA content was unaffected in the 20-micrograms group but was clearly decreased by the higher dose. In the second experiment a statistically significant increase over controls was found in the fraction of labeled ductal cells when 20, 54, and 160 micrograms of cerulein was administered. However, in the acinar cell population an increase was measured only in the 160-micrograms group. A tendency to nadir in cell labeling was observed in both acinar and ductal cell groups at less stimulation. Labeling of centroacinar cells increased in all cerulein-treated groups. The results show that all cell types of the exocrine pancreas can be forced into proliferation by the cholecystokinin analogue used and that there is preferential cell growth stimulation in the ductal and centroacinar cell populations.

Enzyme-specific activities and mineral concentrations of the exocrine pancreas from female SHR/N-corpulent (cp) rats.

A new rodent model, SHR/N-cp, for study of non-insulin-dependent diabetes mellitus (NIDDM) has recently been developed. The present study reports exocrine pancreatic enzyme activities and mineral concentrations in female corpulent (cp/cp) and lean (+/?) rats fed a diet containing carbohydrate as cooked corn starch or sucrose for 7 months to determine the potential of the model for studies of diet and pancreatic function in NIDDM. Although corpulent female rats weighed 2.5 times more than their lean littermates, they consumed less calories when expressed per 100 g body weight than lean rats. Corpulent rats had a significantly smaller relative pancreatic weight than lean rats (p less than 0.0001), but had greater total pancreatic DNA content and concentration (p less than 0.003) and higher pancreatic amylase (p less than 0.0001), lipase (p less than 0.0011), and chymotrypsinogen (p less than 0.0208) specific activities. Corpulent rats had a significantly lower pancreatic copper concentration than their lean littermates (p less than 0.0193). Corpulent rats consuming starch had a higher pancreatic iron concentration than all other experimental groups (p less than 0.05). The corpulent female rats were only mildly diabetic based upon serum and urine indices. The data suggest that the female SHR/N-corpulent rat may be a useful model for studying exocrine pancreatic function of mild cases of non-insulin-dependent diabetes.

Mechanisms of action of alcohol administration on the trophic effect of soybean trypsin inhibitor and cholecystokinin octapeptide in rat

Influence of alcohol administration on the trophic effect of cholecystokinin-octapeptide and soybean trypsin inhibitor administration was examined in male Wistar rats. Two x 4 mL of 20% alcohol given intragastrically during 2 wk did not significantly influence pancreatic weight, DNA, protein, trypsin, chymotrypsin, amylase, lipase, or trypsin inhibitor contents of the pancreas. It diminished the hypertrophy but not the hyperplasia seen after CCK-8 treatment, and eliminated the hyperplasia, as well as the hypertrophy provoked by SBTI administration. Secretory studies and CCK measurements demonstrated decreased CCK release in response to SBTI stimulation after 3-d alcohol administration. The results indicate that alcohol inhibits the enzyme synthesis of the CCK stimulated dividing and/or newly formed acinar cells and the endogenous CCK release.

Effect of estradiol on pancreatic amylase and cholecystokinin binding in ovariectomized guinea pigs

The effect of estradiol (E 2) on amylase content and on basal and stimulated amylase release from the pancreatic acini was examined in relation to its effects on cholecystokinin (CCK)-receptor (R) levels. Guinea pigs were ovariectomized (OVX) and a week later administered either E 2 (10 μg/kg) (Treated, T) or vehicle (corn oil) (Control, C) 0.2 ml/day s.c. After 7 days of injections, animals were killed, pancreata weighed and basal and stimulated amylase release from pancreatic acini measured. Receptors for CCK were measured on pancreatic membranes. Chronic administration of E 2 resulted in a significant decrease in: (1) pancreatic weight (0.96 ± 0.04, T vs 1.142 ± 0.046 g, C); (2) total pancreatic DNA content (5.74 ± 0.37, T vs 6.81 ± 0.16 mgs, C); (3) total amylase content in pancreata (2081 ± 307, T vs 3795 ± 442 I.U., C); (4) absolute value of basal amylase release (6.57 ± 1.4, T vs 11.8 ± 1.9 I.U./incubate, C); and (5) absolute value of amylase release stimulated by increasing doses (0.01–1000 nM) of CCK in T vs C animals. On the other hand, the amylase release in response to >0.5 nM of CCK, expressed as a percentage of the total amylase content, was significantly increased in T vs C animals, which may be related to a significant rise in the concentration (fmol/mg protein) of CCK-receptors (629.8 ± 65.9, T vs 313.4 ± 92.7 fmol, C). Concentration of DNA/unit pancreatic weight and basal amylase release expressed as a percentage of total content, however, was similar in the C and T guinea pigs, while concentration of amylase and CCK-receptors/unit pancreatic weight remained significantly different in the two groups of animals. These results suggest that E 2 may have more than one effect on the pancreas in vivo, including a significant reduction in pancreatic growth and amylase concentration/cell and an up-regulation of CCK-receptors/cell.

Long-term effect of growth promoting conditions on the exocrine pancreas of rats

Pancreatic adaptation following prolonged exposition to growth promoting conditions (protease inhibitor feeding, B II subtotal gastrectomy, subtotal colectomy) was studied in rats. Fifty male Wistar rats were divided into 5 groups: controls (n = 10), sham-operated (n = 10), low dose protease inhibitor feeding (n = 10), B II subtotal gastrectomy (n = 10), and subtotal colectomy (n = 10). After 4 mo a significant increase in pancreatic wet wt and DNA content was observed in rats after protease inhibitor feeding (p less than 0.01), B II gastrectomy (p less than 0.01), and subtotal colectomy (p less than 0.05). Pancreatic total protein and lipase content were significantly increased in these three groups. Amylase and trypsin content increased after feeding the protease inhibitor (p less than 0.01) and following B II subtotal resection (p less than 0.01) but were unaffected after subtotal colectomy. Comparing the long-term effects (4 mo) with our previously published short-term data (4 wk) under the same experimental conditions, pancreatic trophism after 4 mo is less pronounced but characterized by a change in the enzyme composition with an increase in pancreatic lipase content.

PANCREATIC SECRETORY AND TROPHIC RESPONSE TO CAERULEIN IN RATS: EFFECT OF PROGLUMIDE AND LORGLUMIDE

The effect of proglumide and lorglumide, two CCK-receptor antagonists, on caerulein-induced pancreatic secretion and growth was studied in the rat. In anaesthetised animals, caerulein (1 microgram/kg) significantly increased the volume of pancreatic juice and protein output. Lorglumide (5 and 10 mg/kg), administered intraperitoneally 15 min before stimulation, reduced peptide-induced pancreatic exocrine secretion. By contrast, proglumide (100 and 400 mg/kg) was completely ineffective. In experiments dealing with the trophic effect of caerulein, both drugs were administered alone or combined with the peptide (1 microgram/kg) 3 times daily for 5 d. Saline-treated rats served as controls. At the end of the experiment, rats were sacrificed, and growth and composition of pancreatic tissue were determined. Pretreatment of the animals with either proglumide or lorglumide did not affect pancreatic size and composition. Caerulein increased the weight of the pancreas, the total pancreatic protein, trypsin, amylase, and DNA content. After pretreatment with proglumide, all these parameters were not significantly different from those obtained with caerulein alone. In contrast, when lorglumide was given together with caerulein, it significantly reduced caerulein-induced pancreatic growth and decreased enzymatic protein content of the gland. These results show that lorglumide is a much more potent and effective CCK-receptor antagonist than proglumide. Its ability to antagonize the pancreatic secretory and trophic action of a CCK-analogue (i.e. caerulein) supports the view that these physiological actions of CCK are mediated through an interaction of the hormone with specific receptors.

Alterations of pancreatic growth and of GP-2 content in the reserpinized rat model of cystic fibrosis.

The chronically reserpinized rat is an experimental model for cystic fibrosis. In this study, we report the effects of two doses of reserpine (0.5 and 1.0 mg.kg-1.d-1) on the growth of the pancreas and on its content of the glycoprotein GP-2, a characteristic protein of the zymogen granule. An assessment of the effects of secondary malnutrition induced by the drug was also performed by adding a group of pair-fed animals. During the 7 d of treatment, body wt and food intake were monitored. These two parameters were significantly affected from the 4th d on. Pancreatic wt, DNA, protein, and activity of amylase and chymotrypsinogen were measured after 4 and 7 d of treatment; lipase activity and GP-2 content, after 7 d. Although the DNA content never did change, total protein diminished by 27% at the higher dose of reserpine. Pancreatic wt, amylase activity and GP-2 content were reduced by the treatment, while chymotrypsinogen and lipase activities were increased. Effects on pancreatic wt, amylase, chymotrypsinogen, and GP-2 were dose-dependent. Malnutrition had effects similar to reserpine on body wt, protein, amylase, and chymotrypsinogen. Pancreatic wt, lipase, and GP-2, however, were specifically altered by the chronic reserpine treatment. It is concluded from these results that reserpine induces, in the pancreas, specific alterations that are distinguishable from the accompanying malnutrition. These findings support the use of pancreatic wt, lipase, and GP-2 as specific markers of the effects of the drug on the pancreatic tissue in the chronically reserpinized rat model for cystic fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Study into the role of cholecystokinin in bombesin-stimulated pancreatic growth in rats and hamsters

The effects of cholecystokinin and bombesin on growth of the exocrine pancreas have been studied extensively in rats but not in hamsters. Since hamsters are frequently used for studying pancreatic carcinogenesis it seems highly relevant to determine the effects of these peptides on growth of the hamster pancreas as well. In order to determine whether or not bombesin stimulates pancreatic growth in hamsters and to investigate the role of cholecystokinin in mediating this effect, we conducted a 2-week experiment in which cholecystokinin and bombesin were administered to both rats and hamsters, either with or without lorglumide (CR-1409; a specific cholecystokinin receptor antagonist). Rats were included in the study for comparison. Cholecystokinin and bombesin were found to stimulate pancreatic growth and DNA synthesis in both species. Lorglumide did not significantly influence the effect of bombesin on pancreatic weight but did significantly inhibit DNA synthesis in both species. The effect of cholecystokinin on pancreatic weight was greater in hamsters than in rats. This effect was significantly inhibited by lorglumide in hamsters but not in rats, whereas a significant decrease in DNA content was attained in both species. Thus, this study shows marked differences between rats and hamsters in the pancreatic growth response to cholecystokinin and bombesin.

Effect of chronically administered cholecystokinin on the nude mouse

The nude mouse has been used to evaluate the effect of cholecystokinin (CCK) on xenografted tissues, but little is known about long-term actions of cholecystokinin on native organs in this animal. We investigated the impact of chronically administered synthetic cholecystokinin octapeptide on the nude mouse. Six groups of eight animals each received intraperitoneal injections twice daily for 14 days with diluent or a 4-log range of cholecystokinin. Overall health, behavior, and body weight were unaffected by this treatment. Among the seven organs examined at necropsy, pancreas alone showed a dose-related increase in weight. Pancreatic DNA content decreased with increasing dosages of CCK-8, while RNA content exhibited a biphasic response to CCK-8. The only histological abnormality occurred in the pancreas and was confined to the higher doses. These data indicate for the first time the action of CCK on the non-tumor-bearing nude mouse. Unlike other animal models, the nude mouse responds to cholecystokinin administration with pancreatic hypoplasia and hypertrophy, which is accompanied by pancreatitis at higher doses.

Influence of CCK antagonist L-364,718, pancreastatin (33-49) and a somatostatin analogue on camostate-induced rat pancreatic hypertrophy.

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.

Interaction of neurotensin with caerulein or secretin on digestive tract growth in rats

Because neurotensin may potentiate exocrine pancreatic secretory responses to cholecystokinin and secretin, we examined interactions of neurotensin with caerulein or secretin on growth of pancreas, stomach, small intestine, and colon. Rats were injected with saline, neurotensin (100 μg/kg), caerulein (0.67 μg/kg), secretin (100 μg/kg), or neurotensin plus caerulein or secretin every 8 h for 5 days. Pancreas, stomach, small intestine, and colon were weighed and assayed for DNA, protein, and digestive enzymes. Although neurotensin increased pancreatic weight ( P < 0.01), DNA ( P < 0.01), and protein content ( P < 0.05) by 20–30%, it had less than additive effects on responses to caerulein and secretin. Neurotensin had no effects on pancreatic enzymes or on responses to caerulein or secretin. Neurotensin alone had no effects on growth of the oxyntic gland area or antrum but inhibited increases in antral weight, DNA, and protein caused by secretin. Neurotensin increased small intestine weight (9%, P < 0.05) and protein content (23%, P < 0.01). Secretin also increased weight (22%), DNA (29%), and protein content (48%) of the small intestine (all P < 0.01), but neurotensin and secretin together had less than additive effects. Our results suggest that neurotensin inhibits rather than potentiates certain growth effects of caerulein or secretin on the pancreas and other organs.

Trophic responses of the pancreas differ in aging rats.

We previously have shown that the response of pancreatic lipase and amylase to changes in diet composition is altered in senescent rats. The present study was designed to determine if the trophic response to a defined gastrointestinal peptide stimulus differed in 3-month (young) and 27-month (aging) Fischer rats. Caerulein-secretin, administered every 8 h for 7 days, induced pancreatic hypertrophy and hyperplasia as judged by increases in pancreatic weight, protein, and DNA content in both groups. A significant increase also occurred in the content of trypsinogen, amylase, lipase and the polyamines, putrescine, spermine, and spermidine. To quantify differences in the trophic response between young and aging rats, the ratios of data in the treated animals relative to that observed in controls were determined. Pancreatic weight, protein content, and protein DNA ratio increased significantly more in young than in aging treated animals. DNA also increased more but did not reach significance. Pancreatic trypsinogen and lipase content increased significantly more in younger animals, whereas amylase responses were not different between the two groups. Stimulation of pancreatic putrescine and spermidine was also greater in young than in aged animals. We conclude that trophic responses of the pancreas are altered in senescent rats.

Pancreatic polyamine concentrations and cholecystokinin plasma levels in rats after feeding raw or heat-inactivated soybean flour.

We investigated the trophic effect on the pancreas of male Wistar rats fed up to 20 days with either raw soybean flour (RSF) containing an active trypsin inhibitor or heat-inactivated soybean flour (HSF). The concentrations of the polyamines putrescine, spermidine, and spermine in the pancreas as well as cholecystokinin (CCK) concentrations in arterial and portal vein plasma were measured. Plasma CCK concentrations were measured by a sensitive radioimmunoassay specific for the sulfated region of CCK, whereas polyamine concentrations are determined by reversed phase high-performance liquid chromatography. The levels of CCK in both arterial and portal vein plasma were significantly higher in RSF- compared with HSF-fed rats, the concentration in the portal vein being twice as high compared with the aorta. A significant increase in pancreatic weight and protein content was positively correlated to an increase in putrescine and spermidine in the pancreas of RSF-fed rats compared with HSF-fed controls, whereas the spermine content did not differ between the two groups. The pancreatic DNA content in RSF-fed rats was significantly above control values of day 20 only. These data support the hypothesis that the trophic effect of soybean trypsin inhibitor on the pancreas is mediated by CCK and that polyamines might play an important role in CCK-induced pancreatic growth.