Serum gastrin in newborn, sucking and weaned pigs.

Serum gastrin concentrations during the first six weeks of life in pigs reared on sow's milk alone were compared with those in pigs given access to solid food at two weeks and weaned at three weeks of age. Gastrin levels were higher in both parturient sows and newborn unsuckled pigs than in dry sows. It appears that the newborn pig is capable of secreting its own gastrin. High levels of gastrin persisted throughout the experimental period, being particularly high in the first two weeks of life. In weaned pigs, feeding after a period of fasting evoked a greater postprandial gastrin response than that which occurred in unweaned pigs after sucking from the sow. The results suggest a possible role for gastrin in early gastric development.

Anaerobic microflora associated with the pars oesophagea of the pig.

In healthy pigs aged one to 35 days significant populations of microorganisms (5.5 to 6.9 log10 viable count cm-2 of the tissue) were found, by strict anaerobic techniques, to adhere to the pars oesophagea. The genera of anaerobes which were isolated included Actinomyces, Bifidobacterium, Clostridium, Lactobacillus, Peptostreptococcus, Streptococcus and Veillonella and facultative anaerobes included Escherichia, Klebsiella, Staphylococcus, Streptococcus and yeasts. The microbial population adhering to the pars oesophagea varied little from birth till after weaning and Lactobacillus, Clostridium and Eubacterium predominated. There were generally small numbers of facultatively anaerobic microorganisms in the pars oesophagea of healthy sucking or weaned pigs but large numbers of anaerobes, particularly Lactobacillus. In the pars oesophagea of sucking and weaned pigs with diarrhoea, large numbers of facultative anaerobes were frequent but Lactobacillus were also present in large numbers.

Some experimental surgical techniques on the alimentary tract of young pigs.

The paper describes the surgical techniques used in the preparation of gastric, intestinal and caecal fistulae, intestinal re-entrant fistulae, gastric pouches and Thiry-Vella loops. A total of 189 pigs were used in the study ranging from 1 h to 16 weeks of age. All procedures were carried out under cyclopropane/oxygen anaesthesia.

In vitro study of the function of adrenocortical cells from pigs of differing in vivo response to adrenocorticotropin.

A study was conducted to determine whether within-breed differences in adrenocortical response to exogenous adrenocorticotropin (ACTH) might be accounted for by differences in responsiveness of the adrenocortical cells per se. Large White x Landrace male pigs (n = 20) were used; 10 had high adrenocortical response to ACTH administration and 10 had low response. Five high and 5 low responders were euthanatized at 15 weeks of age, and the remaining 5 high and 5 low responders were euthanatized at 21 weeks of age. Adrenal glands were removed and weighed, and adrenocortical cells were dispersed by tryptic digestion and incubated for 2 hours with synthetic ACTH at concentrations ranging from 0.5 to 10,000 pg/ml. Samples were taken at 30-minutes intervals, and cortisol concentration was determined by use of a radioimmunoassay. Results indicate that for pigs of both age groups, high responders had heavier adrenal glands, with higher adrenocortical cell density and higher cell yield than did low responders. Synthetic ACTH had a stimulatory effect on dispersed porcine adrenocortical cells, as indicated by changes in cortisol concentration in vitro. Adrenocortical cells from high responders produced less cortisol, on a per-cell basis, than did those from low responders. However, when corrected for total cell yield, the potential cortisol production by each pair of adrenal glands was significantly (P less than 0.05) higher in the high responders than in the low responders. Thus, high-responding pigs have larger adrenal glands and higher adrenocortical cell density, which may result in higher output of cortisol after ACTH administration or exposure to stressors.(ABSTRACT TRUNCATED AT 250 WORDS)

Pituitary and adrenocortical responses to corticotropin-releasing factor in pigs.

A study was conducted to determine whether differences in adrenocortical response to exogenous adrenocorticotrophin (ACTH) were an accurate reflection of an animal's perception of and response to stressful stimuli, or whether the pituitary gland might modulate adrenocortical responsiveness. Sixteen Large White x Landrace female pigs, of which 8 had high adrenocortical response to ACTH and the other 8 had low response, were administered IV a bolus of synthetic human corticotropin-releasing factor (hCRF) at dose rates ranging from 0.002 to 2 micrograms/kg of body weight. Blood samples were collected at known times for up to 2 hours after administration of hCRF. Plasma ACTH and cortisol concentrations were measured by radioimmunoassay. Results indicate that hCRF stimulated the pituitary gland of high- and low-responding pigs to secrete ACTH, which in turn stimulated the adrenal cortex to secrete cortisol. Plasma ACTH concentration, before or after hCRF administration, was not significantly different between the high and low responders. However, high-responding pigs had higher cortisol concentration after hCRF administration than did low-responding pigs. Thus, the differences in adrenocortical response to ACTH between the 2 groups of pigs were not attenuated by variation in pituitary response. It is concluded that adrenocortical responsiveness to ACTH is an accurate indicator of the perception of and the response to stress.

The development of acid and pepsin (EC 3.4.23.1) secretory capacity in the pig; the effects of age and weaning. 1. Studies in anaesthetized pigs.

The development of gastric secretory capacity of hydrochloric acid and pepsin (EC 3.4.23.1) was studied in thirty-eight Large White X Landrace pigs from the litters of six sows (three pairs of two), 9-38 d of age. The pigs of each pair of sows were born within 24 h of each other. The pigs of a litter were paired according to sex and size and cross-fostered, i.e. one pig from each pair was allocated to each sow. One litter from each pair was reared entirely by the sow (milk-fed, MF) whereas the other litter was reared by the sow for 21 d, but was allowed access to solid food (210 g crude protein (nitrogen X 6.25)/kg) at 12 d and was entirely dependent on solid food after 21 d (creep-fed, CF). Following a 14-18 h fast, pigs were anaesthetized (Halothane-sodium pentobarbitone) and their stomachs perfused at a constant rate with Ringer solution. Gastric secretion was stimulated by intravenous infusion of betazole hydrochloride (Histalog) at 3 mg/kg per h for 2 h. Hydrochloric acid and pepsin were measured in the perfusate which was collected at 15-min intervals. There were significant positive correlations between stomach weight and body-weight for both MF and CF pigs. The slope of the regression line for CF pigs was significantly greater than that for MF pigs (P less than 0.01). There were significant positive correlations between maximal acid output and stomach weight for both MF and CF pigs. There were significant positive correlations between maximal pepsin output and stomach weight for both MF and CF pigs. The slope of the regression line for CF pigs was significantly different from that for MF pigs (P less than 0.01). There were also significant positive correlations between maximal pepsin output per unit stomach weight and stomach weight for both MF and CF pigs. The pattern of development of pepsin secretory capacity in both CF and MF pigs was different from that for acid secretion. Maximal outputs of acid per unit stomach weight for MF and CF pigs remained relatively constant. Maximal outputs of pepsin per unit stomach weight and per unit body-weight increased with age for both MF and CF pigs. The results indicate that pigs given access to solid food before weaning and weaned on to solid food have heavier stomachs and greater acid and pepsin secretory capacity than pigs fed entirely on sows' milk.

Gastrin in fetal and neonatal pigs.

1. The concentration and molecular profile of gastrin were examined in plasma and tissue extracts of fetal and neonatal pigs from 93 days gestation up to 12 weeks of age and also in the fetal gastric contents. 2. Gastrin was present in the gastrointestinal tract and plasma of fetal pigs at 93 days gestation. The concentration in both plasma and antral extracts increased progressively up to birth and continued to rise postnatally, reaching a peak at about 3 weeks of age in plasma and 6 weeks in the antrum. 3. In blood the major molecular form of gastrin was G34 (up to 80%), while in the antrum the major form was G17 (66-91%). The percentage of G34 in the antrum was highest in later gestation (21%), and reached adult proportion by 8 weeks of age (4%). 4. A considerable amount of gastrin, chiefly G17, was detected in the fetal gastric contents. Synthetic human G17 was stable in fetal gastric contents when incubated at 37 degrees C for 60 min, although, when incubated with gastric contents from a sow, it disappeared within 5 min. 5. It is suggested that the presence of gastrin in fetal gastric contents may be important in stimulation of fetal gut development.

Gastrin metabolism in neonatal pigs and grower-pigs.

1. Half-life (1.7 +/- 0.1 min), distribution volume (146 +/- 12 ml/kg) and metabolic clearance rate (28 +/- 1 ml/kg/min) of little gastrin (G17) in neonatal pigs (N = 6; 3-12 days old) were significantly different from those in grower-pigs (N = 4; 161-170 days old) (2.4 +/- 0.1 min; 58 +/- 2 ml/kg; 7.9 +/- 0.3 ml/kg/min, respectively). 2. Half-life (33 +/- 4 min) and distribution volume (265 +/- 33 ml/kg) of big gastrin (G34) in neonatal pigs were greater but not significantly different from those in grower-pigs (24 +/- 2 min; 217 +/- 20 ml/kg, respectively). 3. Half-life of G17 in liver extracts from pigs 2-90 days old (40.4 +/- 4.2 min) was significantly longer than in kidney extracts (22.0 +/- 1.7 min). Half-lives of G34 in liver and kidney extracts from pigs 10-90 days old (78 +/- 6; 74 +/- 4 min, respectively) were significantly shorter than the corresponding values for 2-day-old pigs (134 +/- 3; 149 +/- 9 min, respectively). 4. Since G34 is the major circulating form of gastrin in neonatal pigs the relative longer half-life of G34 to G17 in these animals may contribute to the higher circulating gastrin concentration compared with that in older animals.

Development of gastric acid secretion in pigs from birth to thirty six days of age: the response to pentagastrin.

The development of the gastric acid secretory response to pentagastrin was studied using 56 Large White x Landrace pigs, 0-36 days of age, 1.1-13.3 kg body-weight, obtained from 12 litters. Gastric acid secretory capacity was measured using a gastric perfusion technique and intravenous infusion of pentagastrin at dose rates of 2, 4 and 8 micrograms/h per kg. Significant positive linear correlations were found between stomach weight and age, and between stomach weight and body-weight during the 36 day period. The stomach weight to body-weight ratio increased for the first 3 days of age and then decreased during the following 33 days. Basal acid secretion was detected in all unsuckled pigs (n = 9), 2- to 8-h old. Maximal acid outputs in response to pentagastrin in these pigs were 0.16 +/- 0.02 mmol/kg body-weight and 0.034 +/- 0.001 mmol/g stomach weight. For the 56 pigs, significant linear correlations were found between maximal acid output and age, maximal acid output and body-weight, and maximal acid output and stomach weight. There was a significant linear increase in maximal acid output per unit stomach weight during the first 7 days of age, but during the subsequent 29 days the pattern of increase in gastric secretory capacity was slower and curvilinear. In the oldest nine pigs, 24-36 days of age, maximal acid outputs were 0.974 +/- 0.058 mmol/kg body-weight and 0.234 +/- 0.016 mmol/g stomach weight which represents a six to seven-fold increase compared with those determined in pigs at birth. Comparison of gastric acid secretory capacity determined under anaesthesia with that in conscious pigs showed that anaesthesia appeared to suppress basal output but had no effect on pentagastrin stimulated output. Comparison of response to histalog (betazole HCl) and pentagastrin indicated that newborn pigs were more sensitive to histalog but in pigs 9-38 days of age, there were no significant differences in responsiveness to the two secretagogues. These results show that gastric sensitivity to pentagastrin increases rapidly in the first week of life, that the stomach of the newborn pig is more sensitive to histalog than pentagastrin and that studies of the effect of pentagastrin on acid secretion, done under anaesthesia, are comparable to those in the conscious pig.

An evaluation with piglets of bovine milk, hydrolyzed bovine milk, and isolated soybean proteins included in infant milk formulas. II. Stomach-emptying rate and the postprandial change in gastric pH and milk-clotting enzyme activity.

The piglet was used as a model for the human infant to determine the effect of the protein source of a milk formula on stomach-emptying rate and the postprandial changes in gastric pH and milk-clotting enzyme activity. Three liquid milk formulas containing either intact bovine milk protein, hydrolyzed bovine milk protein, or isolated soybean protein as the sole source of dietary protein were given to five 37-day-old piglets that had undergone surgery for the preparation of a simple gastric fistula. At set times after commencement of a meal, the stomach contents were removed via a gastric cannula and weighed; then pH and milk-clotting enzyme activity were determined. The isolated soybean protein-based formula tended to empty from the stomach more slowly than did the bovine milk-based formulas. Maximum difference (p less than 0.05) was found at 3 h postfeeding, where 30% of the ingested soybean formula dry matter remained in the stomach; comparable values for the intact bovine milk-based formula and hydrolysate were 22 and 12%, respectively. The type of protein did not significantly (p greater than 0.05) affect the postprandial change in gastric pH or gastric milk-clotting enzyme activity. Gastric pH increased sharply after feeding, from pH 1.5 at 0 h to pH 5.2 at 1 h, and then fell gradually over the following 4 h to pH 1.84.

Gastric secretion and fermentation in the suckling pig.

1. The contribution to acidification of the stomach contents of pigs by hydrochloric acid secretion or by lactic acid produced by fermentation was studied in fifteen suckling pigs from six litters born and reared either in a 'conventional' environment or in an isolated 'clean' environment. Sequential samples of stomach contents obtained during periods of up to 24 h were analysed for their chloride and lactic acid contents, pH and total titratable acidity. These values gave a measure of organic and inorganic acids respectively. 2. Six pigs from two litters born and reared in a 'clean' environment had acid secretion in the stomach at 2 d of age, and the concentrations of lactic acid in stomach contents remained low (0-40 mmol/l) throughout the suckling period. 3. Eight pigs from three litters born and reared in a 'conventional' environment, and a ninth pig born in this environment but moved to the 'clean' environment at 24 h of age, had lactic acid in concentrations of up to 250 mmol/l in stomach contents within the 1st week of life. The pattern of lactic acid production (and hence the acidity of stomach contents) was governed by frequency of suckling. 4. Both between- and within-litter variation in the age of onset of HC1 secretion was evident in the group reared in a 'conventional' environment, and when HC1 secretion did occur it was usually accompanied by a reduction in lactic acid production. 5. It is concluded: (1) that the environment at birth is important in determining the fermentative ability of the stomach flora; (2) that if lactic acid is produced in large amounts in the stomach, it may partly or completely inhibit acidification by HC1.

Absorption of lysine and methionine from the proximal colon of the piglet.

The present study aimed to determine whether lysine and/or methionine are absorbed in nutritionally significant amounts from the proximal colon of milk-formula-fed piglets (15-32 d old; 2.0-7.4 kg liveweight). Piglets, surgically prepared with simple catheters which allowed infusion into the proximal colon, were randomly allocated to one of two milk-formula diets which were either 40% deficient in lysine (L-diet) or 60% deficient in methionine and 40% deficient in cysteine (S-diet), yet balanced for all other amino acids. The piglets were individually bottle-fed the milk-formula diets seven times daily at 2 h intervals between 08.00 and 20.00 hours. Physiological saline (9 g NaCl/l) or an isotonic solution containing the deficient amino acid was infused via the catheter at each feeding. The experimental procedure followed a cross-over design. Total daily excretions of urinary urea and total N were determined. There were no significant differences (P > 0.05) in urinary N metabolite excretion for piglets infused with amino acids compared with those infused with saline. Lysine and methionine do not appear to be absorbed in nutritionally significant amounts from the proximal colon of the milk-fed piglet.

Development of gastric proteases in fetal pigs and pigs from birth to thirty six days of age. The effect of adrenocorticotropin (ACTH).

Development of the synthesis and secretion of gastric proteases was studied in 55 Large White x Landrace pigs from 22 days before birth (93 days gestation) to 36 days of age. The pigs came from eight litters and were 0.4 - 13.5 kg body weight. Littermate pairs were treated with either saline or adrenocorticotropin (ACTH) from three days of age. Secretion of protease activity (milk-clotting and general proteolytic activity) was investigated in anaesthetized pigs by a gastric perfusion technique using intravenous infusion of pentagastrin at dose rates of 4 and 8 micrograms/h per kg body weight. In addition, concentrations of protease zymogens (prochymosin, pepsinogen A, progastricsin) were measured in fundic tissue extracts by rocket immunoelectrophoresis. Prochymosin was present in fundic tissue at 22 days before birth, reached peak concentrations at birth and decreased in concentration during the subsequent 36 days. Pepsinogen A and progastricsin were absent or present in trace amounts in the first week after birth, but thereafter concentrations of both zymogens increased rapidly. Development of the pentagastrin-stimulated secretion of protease activity reflected the changes of zymogen concentrations in fundic tissue. Chronic treatment of pigs with ACTH from three days of age significantly increased the concentration of prochymosin in fundic tissue at 9-11 days and the concentrations of pepsinogen A and progastricsin at 34-36 days of age. Hormones such as ACTH and glucocorticoids may therefore play a regulatory role in the ontogeny of porcine gastric proteases.

Ontogeny of gastric function in the pig: acid secretion and the synthesis and secretion of gastrin.

Gastric acid secretion, gastrin-releasing peptide (GRP)-stimulated gastrin secretion and concentrations of somatostatin in gastric tissues were studied in sucking pigs (n = 48). In addition, gastrin concentrations in plasma and antral tissue were measured in fetal and sucking pigs (n = 66) from 22 days before birth (93 days gestation) to 36 days of age. From 3 days of age littermate pairs were treated twice a day with either saline (n = 20) or adrenocorticotropin [ACTH (1-24); n = 20]. Pentagastrin-stimulated acid secretion per unit stomach weight was 39 +/- 7 mumol H+/g/h at 0-1 day, increased to 194 +/- 15 mumol H+/g/h at 5-7 days and plateaued. Antral gastrin concentration was 0.14 nmol/g 10 days before birth and increased to 2.7 nmol/g at 5 weeks of age. Plasma gastrin was 25 +/- 2 pmol/l at 22 days before birth, increased to 102 +/- 14 pmol/l at birth and decreased during the postnatal period. Somatostatin concentrations were higher in antral than fundic tissues (p < 0.05) and remained constant during the postnatal period. Increased levels of glucocorticoids in plasma following ACTH treatment had no effect on the studied parameters except that it reduced basal (p < 0.07) and GRP-stimulated (p < 0.05) plasma gastrin concentrations at 6-7 days of age. Development of acid secretion and its gastric regulatory peptides in the pig is different from that in the rat in that it occurs at an earlier age and does not appear to be greatly influenced by elevated glucocorticoid levels from 3 days after birth.

Effect of intraluminal pH on the release of somatostatin and gastrin into antral, bulbar and ileal pouches of conscious dogs.

Experiments were performed on conscious dogs with chronic pouches of the antrum, the duodenal bulb or the ileum, which were perfused with solutions of varying pH. Gastrin and somatostatin levels were measured in the perfusates. When the pouches were perfused with 0.15 M NaCl only small amounts of gastrin and somatostatin (1 pmol/min) were released into the lumen of the antrum and of the duodenal bulb. By lowering pH of the perfusion fluid a pH dependent release of somatostatin was induced into the lumen of the antrum and the duodenal bulb. Perfusion with 0.1 M HCl caused a large output of somatostatin (6--60 pmol/min) into the pouches. The upper pH limit for stimulation of the intraantral or intrabulbar somatostatin release appeared to be approximately pH 3--4. Somatostatin was also released into ileal perfusates at intraluminal pHs below 3--4. Lowering of pH in the antral pouches caused an increased intraluminal gastrin release, which was quantitatively less impressive than that of somatostatin. Occasionally also the gastrin release into the duodenal bulb increased during perfusion with 0.1 M HCl, whereas no such release was induced by acidification of the lumen of the ileum. It is suggested that the inhibition of gastrin release observed at low intraantral pH is mediated by a local effect of somatostatin, since this peptide is released in a pH dependent manner in the antropyloric region. It is also suggested that acidification of any region of the gastrointestinal tract will stimulate the release of peptides from all endocrine cells of the open type, probably by an unspecific effect on the membrane. Thus both gastrin and somatostatin are released by acidification of the antrum, but in the presence of high local levels of somatostatin, the release of gastrin is substantially inhibited.

Adrenocortical ACTH receptors in pigs of differing in vivo response to adrenocorticotropin.

1. Adrenocortical membrane protein was isolated from the adrenal glands of 12 Large White x Landrace male pigs, six with high adrenocortical response to adrenocorticotropic hormone (ACTH) and six with low response. 2. The peptide (Phe2, Nle4) ACTH was iodinated by the chloramine-T method and served as the radioligand in receptor binding studies. 3. Only one class of ACTH receptor was detected, with Kd = 2.57 +/- 0.35 x 10(9) M and Bmax = 1.59 +/- 0.06 pmol/mg protein in high responders and Kd = 1.68 +/- 0.18 x 10(-9) M and Bmax = 1.17 +/- 0.11 pmol/mg protein in low responders. 4. The difference in the Bmax between high and low responders was significant (P < 0.05), the difference in Kd was not statistically significant.