Pancreatic enzyme deficiency depends on dietary protein origin in milk-fed calves.

In young mammals, milk proteins and their substitutes are used in milk formula. Protein substitution modifies diet digestibility and pancreatic secretions. The aim of this study was to test if milk protein substitution could generate pancreatic deficiency in milk-fed calves. The effect of pancreatic juice on the digestibility of proteins was studied. Measurement of apparent fecal nutrient digestibility was used to estimate digestion. Ten calves (60 to 130 d old) were chronically fitted with pancreatic accessory duct cannulas and 2 duodenal cannulas to provide precise measurement, sampling, and reintroduction of pancreatic juice as well as additional infusions. Animals were fed milk formula based on skim milk powder or soybean concentrate. Level of deficiency depended on dietary protein origin. Twice as much protein or trypsin was required with a soybean concentrate diet than with a skim milk powder diet to obtain maximal nutrient digestibility. Pancreatic protein concentration in the juice can be used to differentiate between normal and deficient animals. Among these proteins, trypsin measurement is a good pancreatic deficiency marker. These results confirmed the major role of exocrine pancreatic secretions in producing optimal digestion in young calves. Furthermore, practical applications of these results can be applied for the young in other animal species and in humans.

Dietary sodium butyrate supplementation increases digestibility and pancreatic secretion in young milk-fed calves.

The aim of this study was to test, in 8 calves fed milk formula based on soybean protein, the ability of sodium butyrate (SB) supplementation to improve nutrient digestibility and daily pancreatic secretions and to modify the kinetics of these secretions. Additionally, effects of duodenal SB infusion were evaluated. Plasma levels of gastrin, secretin, and cholecystokinin were measured. Butyrate supplementation in milk formula increased nutrient digestibility and total daily pancreatic secretions. For juice volume, this increase was most important from 12 to 17h after the morning meal. During the 3-h postprandial period, oral SB supplementation reduced the physiological decrease of postprandial pancreatic secretion (while duodenal digesta flow rate was maximal) and had a minor effect on plasma gut regulatory peptide concentrations. Compared with the diet without SB, ingestion of SB stimulated pancreatic secretion. Taken together, these results could explain the measured increase in nutrient digestibility. The data obtained after duodenal SB infusion did not indicate an effect on pancreatic secretion, apart from elevated lipase output compared with control. The mechanisms responsible for these events are not known and circulating gut regulatory peptides do not seem to be implicated. Our work brings new results regarding SB as a feed additive in young calf nutrition.

Differential expression of A- and B-subtypes of cholecystokinin/gastrin receptors in the developing calf pancreas.

Cholecystokinin (CCK)/gastrin receptors were characterized in calf pancreatic plasma membranes from newborns, 28- and 119-day-old milk-fed preruminants, and 119-day-old weaned ruminants. Scatchard analysis of [125I]Bolton-Hunter reagent-[Thr28,Nle31]CCK-(25-33) binding indicated two classes of binding sites: high affinity sites exhibited significant higher affinity and binding capacity (P < 0.05) in 119-day-old ruminants than in 119-day-old preruminants (Kd = 0.13 +/- 0.02 vs. 0.35 +/- 0.08 nM; binding capacity (Bmax) = 53 +/- 12 vs. 18 +/- 5 fmol/mg protein). Pharmacological analysis using selective agonists and antagonists indicated the expression of the CCK-A receptor at birth, whereas the CCK-B receptor predominated at postnatal stages. At all stages, the binding was inhibited by guanosine 5'-[gamma-thio]triphosphate. Binding site identification by photoaffinity labeling showed that at birth, the labeling occurred mainly on a 78- to 96-kilodalton (kDa) component. In milk-fed animals, aged 28 and 119 days, two membrane-binding components were labeled at 78-96 and 43-52 kDa. In 119-day-old ruminants, labeling occurred mainly on a 40- to 47-kDa protein. Deglycosylation by endo-beta-N-acetylglucosaminidase-F of the 40- to 47- and 43- to 52-kDa components resulted in the formation of a 37-kDa membrane protein. Consequently, this study demonstrated 1) the differential expression of CCK-A and -B receptors in developing calf pancreas, 2) the predominance of CCK-B receptors in normal pancreas, and 3) the maturation of CCK-B receptors during the weaning period, which includes the glycosylation level. These results suggest that CCK may play a predominant role during the early postnatal development, while gastrin and CCK-B receptors can function progressively to regulate proliferation and exocrine secretion in the calf pancreas, especially from the weaning period.

Specific regulation of pancreatic elastase I and II mRNA expression during postnatal development in the calf: reverse transcriptase-polymerase chain reaction analysis.

The specific regulation of pancreatic elastase I and II mRNA expression as well as of the protein, RNA, and DNA contents were determined during ontogeny in the calf. Specific activities and mRNA concentrations were quantified by spectrophotometry and reverse transcriptase-polymerase chain reaction, respectively. Calves were either milk-fed or weaned until slaughter at different ages. The biosynthesis of elastases I and II was modulated by postnatal development and weaning, leading to specific gene expression profiles. The levels of elastase I activity and of the corresponding mRNAs were found to evolve in a roughly similar way. On the contrary, elastase II activity level decreased sharply during postnatal development, while no changes were observed in the corresponding mRNA levels. After weaning, elastase I activity and mRNA levels, as well as elastase II mRNA levels, increased. However, the magnitudes of elastase I activity and mRNA inductions were different. Therefore, the expression of each gene in the calf pancreas is more or less independently regulated and the regulation is mainly pretranslational (elastase I) or translational (elastase II) during postnatal development and both pretranslational and translational at weaning. The translational efficiency of elastase I and II mRNAs might be influenced by the nature of dietary proteins.

Local and systemic immune responses to soybean protein ingestion in early-weaned pigs.

The development of local and systemic immune responses to soybean proteins was investigated in early-weaned pigs. Pigs were given either antigenic (ASP, n = 10 pigs) or non-antigenic (NASP, n = 8 pigs) soybean products (6 g of protein/d) from d 5 to 9 of age by stomach tube. After weaning at d 21, pigs were fed diets containing the corresponding soybean products and slaughtered between d 28 to 30. Diarrhea was 2.4-fold more frequent, the size of duodenal villi was reduced by 24 to 36%, and the eosinophil density in the duodenal mucosa was 13 times greater (P < .02) in the ASP pigs compared with the NASP pigs. A larger erythema area (P = .006) was observed in the ASP group than in the NASP group 30 min after an intradermal injection of glycinin, but no significant difference could be detected with alpha- or beta-conglycinin or whole soybean extracts. No difference in skin fold thickness was apparent between groups 24 h later. Intestinal, mesenteric lymph node, and blood lymphocytes did not proliferate when cultured with soybean proteins, regardless of dietary treatment. By ELISA, no difference between groups was observed in the circulating levels of total immunoglobulins (Ig) and IgM. Immunoblotting patterns of raw soybean with sera from 28-d-old pigs showed two bands (22 and 36 kDa) recognized by IgA and IgM, respectively, in the ASP group only. Finally, the adverse effects observed with antigenic soybean flour can be overcome by the use of alcohol-treated products.(ABSTRACT TRUNCATED AT 250 WORDS)

Preterm as compared with full-term neonatal calves are characterized by morphological and functional immaturity of the small intestine.

Intestinal diseases in neonatal calves may be due to morphological and functional immaturity. We have studied histomorphology, crypt cell proliferation rates (based on incorporation of 5-bromo-2'-deoxyuridine into DNA), presence of apoptotic cells (based on terminal deoxynucleotidyl transferase-mediated X-dUTP nick end labeling), and brush border enzyme activities in preterm calves (277 d of gestation), euthanized on d 1 (P0) or 8 (P8), and in full-term calves (290 d of gestation), euthanized on d 1 (F0) or 8 (F8). Vacuolated epithelial cells were present in ileum of P0 and F0 but not in P8 and F8. During the first 8 d, villus sizes, crypt depths, and proliferation rates of crypt cells in the small intestine of preterm calves did not significantly change. In contrast, in full-term calves during the first 8 d, villus sizes in jejunum decreased, crypt depths increased in small intestine and colon, and crypt cell proliferation increased in duodenum and jejunum. Submucosal thickness in jejunum was highest in P0, but in ileum it increased with gestational age and feeding. Gestational age x feeding interactions indicated increased activities of aminopeptidase N and reduced lactase activities only in F8 and reduced dipeptidylpeptidase IV activities only in P8. In conclusion, in preterm calves the small intestinal epithelium was immature and brush border enzyme activities differed in part from those in full-term calves.

Effect of sodium butyrate on the small intestine development in neonatal piglets fed [correction of feed] by artificial sow.

Feeding of neonates with artificial milk formulas delays the maturation of the gastrointestinal mucosa. Na-butyrate has a complex trophic effect on the gastrointestinal epithelium in adults. The present study aimed to determine the effect of milk formula supplementation with Na-butyrate on the gut mucosa in neonatal piglets. Sixteen 3 day old piglets were randomly divided into two groups: control (C, n = 8), and Na-butyrate (B, n = 8). Animals were feed for 7 days with artificial milk formula alone (C) or supplemented with Na-butyrate (B). At the 10(th) day of life the piglets were sacrificed and whole thickness samples of the upper gut were taken for analyses. Administration of Na-butyrate led to significant increase in daily body weight gain as compared to control. In the duodenum, the villi length and mucosa thickness were reduced, however, in the distal jejunum and ileum, the crypt depth, villi length and mucosa thickness were increased in Na-butyrate supplemented piglets as compared to control. Supplementation with Na-butyrate did not affect the intestinal brush border enzyme activities but increased plasma pancreatic polypeptide and cholecystokinin concentrations. These results suggest that supplementation with Na-butyrate may enhance the development of jejunal and ileal mucosa in formula-fed piglets.

Diet modifies elastase I and II activities and mRNA levels during postnatal development and weaning in piglets.

Little information is available on the expression of pancreatic elastase I and II, despite their role in protein milk digestion. We studied the developmental changes and the effects of diet composition on both elastase I and II expression in suckled and weaned piglets. We measured their activities and levels of their corresponding mRNA. Forty-two piglets were assigned to seven groups according to age and diet. Piglets were slaughtered at birth (Group 1), or suckled up to 13 d (Group 2) or 21 d (Group 3), fed a milk substitute from 14 to 21 d (Group 4) or to 56 d (Group 7), suckled up to 21 d and then fed a dry starter up to 56 d (Group 5), or fed a milk substitute from 14 to 21 d and then a dry starter up to 56 d (Group 6). At 21 d pancreatic function was not modified by the source and the form of milk consumed. The specific activity of elastase II was maximum at birth and declined sharply thereafter, whereas that of elastase I markedly increased after weaning. The presence of milk protein in the diet did not prevent the sharp decrease in elastase II activity observed with age. During the 13 d period of suckling sow's milk, the mRNA patterns indicated that the regulation was at the mRNA and post-transcriptional levels, whereas after weaning and depending on the source of dietary protein, it was essentially translational and/or post-translational. Taken together, our results provide evidence of the early expression of elastase I and II genes that could enhance protein digestion. It seems that elastase II might be a predominant pancreatic protease during the milk-feeding period, whereas elastase I might be related to weaning.

Source of dietary protein influences kinetics of plasma gut regulatory peptide concentration in response to feeding in preruminant calves.

The kinetics of the peripheral plasma concentrations of eight gut regulatory peptides were examined in response to feeding in preruminant calves. Two experiments were carried out in animals fed milk substitutes either based on milk protein (control diet) or in which casein had been replaced by hydrolyzed fish (fish diet in experiment 1) or whey (whey diet in experiment 2) protein concentrate. In contrast to the control diet, the latter two did not coagulate within the abomasum. No variation was observed in plasma concentrations of gut regulatory peptides during 1-1.4 hr before the morning meal regardless of the nature of the dietary protein. With the control diet, the meal was followed by an increase in cholecystokinin, gastrin and gastric inhibitory polypeptide and a fall in secretin, vasoactive intestinal polypeptide and motilin, whereas no significant change was observed for somatostatin and pancreatic polypeptide. The replacement of casein by protein substitutes did not greatly modify the pattern of plasma responses to feeding, but the prefeeding and postfeeding levels were highly affected. We conclude that the most important characteristic influencing plasma gut peptide concentrations is the ability of dietary protein to clot in the abomasum, consequently determining the pattern of gastric emptying, and that variations appear depending on the origin of protein substitutes in relation to the duodenal content and mainly to the digesta pH.

Pancreatic secretory response to feeding in the calf: CCK-A receptors, but not CCK-B/gastrin receptors are involved.

In bovine species, as in human, the pancreas predominantly expresses cholecystokinin-B (CCK-B)/gastrin receptors. However, the role of this receptor in the regulation of meal-stimulated pancreatic enzyme release has not been determined. In milk-fed calves, we previously described prandial patterns of exocrine pancreatic secretion and a long prefeeding phase was observed. The present study was aimed at determining both the role of external stimuli in the outset of the prefeeding phase and the implication of pancreatic CCK-A and CCK-B/gastrin receptors in the mediation of pancreatic response to feeding. The first objective was studied by suppressing external stimuli associated with food intake (unexpected meal) and the second by infusing highly specific and potent antagonists of CCK-A (SR 27897) and CCK-B/gastrin (PD 135158) receptors during the prandial period. When calves were given an unexpected meal, the long prefeeding increase in pancreatic secretion was absent. SR 27897 (but not PD 135158) inhibited the preprandial phase and greatly reduced postprandial pancreatic juice and enzyme outflows. The expectancy of a meal seemed to elicit an increased pancreatic response right before a meal and CCK-A receptors may mediate this information via neural pathways. The implication of CCK and CCK-A receptors in mediating the postfeeding pancreatic response was also demonstrated. The participation of CCK-B/gastrin receptors in this regulation was not demonstrated.

Feeding colostrum, its composition and feeding duration variably modify proliferation and morphology of the intestine and digestive enzyme activities of neonatal calves.

We studied the effects of amounts of colostrum consumed on intestinal morphology and proliferation and digestive enzyme activities in neonatal calves. Group GrCmax calves were fed colostrum from the first milking undiluted on d 1-3 and diluted with 25, 50, 75 and 75 parts of a milk replacer on d 4-7. Group GrC1-3 calves were fed colostrum from milkings 1-6 up to d 3 and then a milk replacer up to d 7. Group GrF1-3 calves were fed a milk-based formula (containing only traces of growth factors and hormones) up to d 3 and then a milk replacer up to d 7. Calves were killed on d 8. Differences in feeding affected villus sizes and villus height/crypt depth ratios in the duodenum (GrCmax > GrC1-3), villus areas and villus height/crypt depth ratios in the jejunum (GrC1-3 > GrF1-3) and crypt depths in the colon (GrF1-3 > GrC1-3). Furthermore, different feeding protocols affected the proliferation rates of epithelial cells in the duodenum (GrC1-3 > GrCmax; GrC1-3 > GrF1-3) and the jejunum (GrF1-3 > GrC1-3; based on Ki-67 labeling). Lipase activities in the pancreas were influenced by colostrum feeding (GrC(max) > GrC(1-3)). Colostrum intake differentially affected intestinal epithelial surface and proliferation and enzyme activities. Feeding high amounts of first colostrum seemed to enhance the survival of mature mucosal epithelial cells in selected parts of the small intestine, whereas the lack of colostrum seemed to decrease epithelial growth.

Comparison of the kinetics of pancreatic secretion and gut regulatory peptides in the plasma of preruminant calves fed milk or soybean protein.

Exocrine secretion from the pancreas and concentrations of cholecystokinin, gastrin, secretin, and somatostatin in plasma were measured in relation to feeding in 70- to 120-d-old preruminant calves fed either a milk diet or a soybean diet. Pancreatic fluid was continuously collected, measured, and reintroduced in catheterized calves. Blood samples were withdrawn for measurements of gut regulatory peptide concentrations in plasma. A slight increase in outflow of pancreatic fluid was observed 30 min before the milk diet was introduced but not before the soybean diet was fed. In contrast, concentrations and outflows of protein and trypsin immediately after feeding were higher when calves were fed the soybean diet. Overall, during the first 5 h postfeeding, the outflow of pancreatic fluid was 40% higher when the milk diet was fed than when the soybean diet was fed. No difference in outflow of protein was observed, but that of trypsin was 82% higher when the soybean diet was fed. This enhanced enzyme secretion could have been related to the increased plasma concentrations of gastrin and cholecystokinin after the soybean diet was fed. Secretin release was less in calves fed the milk diet that in calves fed the soybean diet during the first 2 h postfeeding, suggesting that this gut peptide along with gastrin and cholecystokinin, contributed to the stimulation of enzyme secretion. Plasma gut regulatory peptides could be influenced by the soybean diet, which does not coagulate in the stomach, inducing faster gastric emptying of protein and fat, and by the chemical form of protein from the soybean diet and the lower susceptibility of these proteins to protease compared with casein. However, the resulting enhancement of pancreatic trypsin secretion and activity seemed to be insufficient to increase the digestibility of soybean protein up to a level similar to that of milk.

Intestinal development in neonatal calves: effects of glucocorticoids and dependence of colostrum feeding.

The neonatal development of the gastrointestinal tract around parturition in precocious mammals is greatly affected by endocrine factors like glucocorticoids as well as by nutritional factors. We have studied the effects of glucocorticoids and colostrum supply on intestinal morphology, cell proliferation, digestive enzyme activities, and xylose absorption in neonatal calves to test the hypothesis that the intestinal development in neonatal calves is influenced by glucocorticoids, dependent on colostrum feeding. Calves designated GrFD(-) and GrFD(+) were fed a milk-based formula, whereas those designated GrCD(-) and GrCD(+) received colostrum. Dexamethasone (DEXA; 30 microg/kg/day) was injected at feeding times to calves of GrFD(+) and GrCD(+). On day 3, the D-xylose absorption was measured. The calves were euthanized on day 5 of life. Colostrum feeding increased villus sizes in jejunum and ileum, enhanced xylose absorption capacity, and increased peptidase activities in the ileum. DEXA treatment diminished sizes and cell proliferation rates of Peyer's patches in the ileum, yet increased proliferation of crypt cells in the ileum of formula-fed calves. DEXA reduced aminopeptidase N activities in the jejunum of formula-fed calves, but increased the peptidase activities mainly of colostrum-fed calves in the ileum. Thus, DEXA effects depended on intestinal segment and on different feeding, resulting in stimulation of crypt cell proliferation in the less mature ileum (of formula-fed calves) and in stimulation of peptidase activities in the more mature ileum (of colostrum-fed calves). We conclude that the effects of DEXA were related to the developmental stage of the neonatal intestine and promoted the intestinal development, depending on the developmental stage.

The CCKB/gastrin receptor is coupled to the regulation of enzyme secretion, protein synthesis and p70 S6 kinase activity in acinar cells from ElasCCKB transgenic mice.

In order to determine which physiological functions can be regulated by the pancreatic CCKB/gastrin receptor, studies were carried out on pancreatic acini from mice expressing transgenic CCKB/gastrin receptors in the exocrine pancreas (ElasCCKB mice). Acini were stimulated by sulfated gastrin in the presence of SR 27897 (1.8 microM), blocking endogenous CCKA receptors. After 30 min incubation with gastrin, the secretion of chymotrypsinogen and amylase showed superimposable monophasic dose-response curves. Enzyme secretion was detectable and maximal at 100 pM and 1 nM of gastrin, respectively. No increase in chymotrypsinogen and amylase mRNAs was detected for doses of gastrin which specifically occupy the CCKB/gastrin receptor. In contrast, gastrin stimulated total protein synthesis in isolated acini from ElasCCKB mice. [35S]Methionine incorporation into total proteins was increased dose-dependently to a maximum for 30 pM gastrin and inhibited with higher doses (> 300 pM). Gastrin stimulated p70 S6 kinase activity for concentrations ranging from 10 pM to 1 nM. Gastrin-stimulated p70 S6 kinase activity and protein synthesis were blocked by rapamycin and wortmannin. Therefore, in ElasCCKB mice acinar cells, the CCKB/gastrin receptor mediates enzyme release and protein synthesis. However, a more efficient coupling of the CCKB/gastrin receptor to protein synthesis than to enzyme secretion was demonstrated. CCKB/gastrin receptor-stimulated protein synthesis likely results from an enhancement of mRNA translation and involves phosphatidyl inositol 3-kinase and p70 S6 kinase.

Response of the calf pancreas to differently processed soya bean and pea diets.

The purpose of this study was to determine the effect of replacing skim-milk powder by differently treated soya bean or pea products on growth, pancreas size and pancreatic enzyme activities in calves. Three separate experiments have been performed. In experiments 1 and 2, 28 and 21 male Holstein calves were divided into 4 or 3 groups, respectively, and fed either dairy products or milk substitutes in which protein was mainly provided by soya bean products differing in their protein concentration due to the technological processing applied. In experiment 3, 45 male Holstein calves were divided into 3 groups and were fed either dairy products, or raw or flaked pea flour as a protein source. After an experimental period of 99 +/- 4 days in experiments 1 and 2, and of 88 days in experiment 3, animal growth rate was significantly lower with raw pea flour (16%) and with the soya bean diet, which was highly concentrated in carbohydrates and allergenic proteins (13-27%). Pancreas weight decreased significantly (16-18%) with pea diets and tended to be lower (NS) with the water extracted, concentrated and heated flour (soya bean). Amylase-specific activity increased significantly (43%) with pea diets but showed opposite tendencies with the most refined soya bean products. Proteolytic enzyme activities were slightly influenced by dietary protein source, but this was not as obvious as in the literature reviewed. Specific messenger RNAs corresponding to amylase, trypsin and chymotrypsin seemed to increase (NS) with the soya bean diets, particularly with the less elaborated one. However, further investigations are required before any conclusions may be drawn concerning regulation levels of pancreatic adaptation to dietary protein. According to this study and the literature, results concerning pancreatic response to diets were different suggesting that the origin of soya bean, pea seeds and technological treatments applied to them were of great importance. Also, the level of incorporation into milk substitute and the presence of more or less antinutritional factors could influence pancreatic enzyme variations by complex mechanisms.

Exogenous CCK and gastrin stimulate pancreatic exocrine secretion via CCK-A but also via CCK-B/gastrin receptors in the calf.

A predominance of the pancreatic cholecystokinin (CCK) receptor of the B/gastrin subtype (CCK-B/G) was reported in calves older than 1 month. Specific CCK-A and CCK-B/G receptor antagonists (SR 27897 and PD 135158, respectively) were used to identify the CCK receptor subtype involved in exogenous CCK- and gastrin-induced exocrine pancreatic responses. Conscious calves (2 months old) with catheterized pancreas, jugular vein and duodenum were used; the pancreatic juice was continuously reinfused. CCK (30 pmol kg-1 min-1, 40 min) evoked an increase in pancreatic juice flow and enzyme secretion, while the same dose of gastrin increased enzyme secretion alone. CCK-induced pancreatic secretion was abolished by SR 27897 (15 nmol kg-1 min-1, 55 min) and reduced by PD 135158 (0.15 nmol kg-1 min-1, 55 min). Gastrin-induced enzyme secretion was reduced by PD 135158 (50% to 90%) and to a lesser extent by SR 27897 (50% to 60%). These results demonstrate that CCK and gastrin in the physiological range stimulate pancreatic exocrine secretion in calves and that these effects are partly mediated by CCK-B/G receptors. Although CCK-A receptors are not predominantly expressed, they seem to play a major role in the response of pancreatic exocrine secretion to CCK.

Gut regulatory peptide levels in bovine fetuses and their dams between the 3rd and 9th months of gestation.

Several gut regulatory peptides were measured by radioimmunoassay between 3 and 9 months of gestation in the plasma of 91 bovine fetuses and their dams, in fetal gastric content and in amniotic fluid. During gestation, plasma peptide concentrations did not change in cows. Likewise, fetal plasma concentrations of cholecystokinin, somatostatin, secretin and vasoactive intestinal polypeptide showed no variation while those of gastrin, pancreatic polypeptide and gastric inhibitory polypeptide increased during the last 6 months. Peptide levels in the fetus were higher than or equal to maternal concentrations. At 8-9 months of gestation, gastrin, CCK, secretin and somatostatin concentrations in amniotic fluid were lower than those measured in fetal gastric content and in maternal and fetal plasma. Therefore, a substantial endogenous endocrine production of regulatory peptides by the fetus probably exists as early as the third month of gestation, accompanied by a release into the lumen of the gut.

Kinetics of pancreatic exocrine secretion and plasma gut regulatory peptide release in response to feeding in preruminant and ruminant calves.

Pancreatic exocrine secretion and plasma cholecystokinin, gastrin, secretin, and somatostatin concentrations were examined in relation to feeding in 70- to 120-day-old preruminant and ruminant calves. The apparatus used was designed to immediately re-infuse the animal's own pancreatic juice and to carry out accurate measurements of the juice flow in real time and to take samples. In the preruminants, pancreatic juice, protein, and trypsin flows increased from 45 min before and until 15 min after the meal and decreased sharply thereafter over a period of 30 min. while protein and trypsin concentrations peaked after feeding. A significant increase in plasma gastrin and cholecystokinin (CCK), a fall in secretin and no change in somatostatin were observed after milk ingestion. By contrast, in the ruminants, feeding had no effect on the pancreatic secretion and on the plasma concentrations of these peptides. Similar and simultaneous patterns of juice flow and secretin, as well as of protein and trypsin concentrations, CCK and gastrin, could support the hypothesis that these gut regulatory peptides play a significant role in the regulation of the pancreatic function. In preruminant calves, the existence of cephalic, gastric and intestinal phases is discussed. In the ruminants, that of the ruminal phase is questionable.