bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of the small intestine and gastric antrum in pancreatic polypeptide release
Authors: Taylor I. L. , Kauffman G. L. , Walsh J. H. , Trout H. , Chew P. , Harmon J. W.
Published: December 2017

Gastrointestinal peptides have been proposed to play an important role in the pancreatic polypeptide response to a meal. These studies examine the role of the small intestine and gastric antrum in pancreatic polypeptide release in unanesthetized dogs. Intestinal perfusion with 5% liver extract in seven dogs resulted in a significant increase (P less than 0.05) in serum pancreatic polypeptide concentration (mean delta PP = 35.0 +/- 10.5 pM). Antrectomy without truncal vagotomy in four of these dogs significantly inhibited (P less than 0.05) this response. In five other dogs, antrectomy inhibited the pancreatic polypeptide response to an ingested meat meal by 81.9 +/- 4.5% (P less than 0.01). To further delineate the mechanism by which antrectomy inhibits pancreatic polypeptide release, the pancreatic polypeptide response to a meal was measured in four dogs before and after selective antral denervation. Antral denervation inhibited pancreatic polypeptide release to a degree similar (81.5 +/- 13.4%) to that previously observed after antrectomy. These studies have demonstrated an intestinal phase of pancreatic polypeptide release. They also suggest that antrectomy exerts its inhibitory effect on pancreatic polypeptide release by partially denervating the pancreas.
Alkaline secretion by amphibian duodenum. I. General characteristics
Authors: Simson J. N. , Merhav A. , Silen W.
Published: December 2017

Stripped, proximal bullfrog duodenum was mounted in an Ussing chamber between HCO3--buffered nutrient (serosal) and unbuffered secretory (luminal) solutions. This preparation showed stable electrical parameters and caused alkalinization of the secretory solution at a rate of 0.95 +/- 0.03 mueq.cm-2.h-1 (mean +/- SE; n = 100). Anoxia and 2,4-dinitrophenol each reduced alkalinization by 50–60%, but acetazolamide (5 X 10(-4)M) had no effect. Removal of nutrient HCO3- and CO2 reduced alkalinization by over 90%, whereas increasing nutrient [HCO3-] at constant partial pressure of CO2 (PCO2) or increasing nutrient PCO2 at constant [HCO3-] each caused saturable increases in alkalinization, despite opposite effects on nutrient pH. Dibutyryl adenosine 3',5'-cyclic monophosphoric acid, but not dibutyryl guanosine 3',5'-cyclic monophosphoric acid, increased luminal alkalinization to 167 +/- 21% of control. Removal of nutrient, but not secretory, Na+ reduced alkalinization by 74%. Changes in the rate of alkalinization were accompanied by corresponding changes in potential difference and short-circuit current. Removal of Cl- or nutrient K+ or addition of histamine, thiocyanate, or catecholamines had no effect on electrical or secretory characteristics. We conclude that a) the amphibian duodenum transports alkali from nutrient to secretory solutions by both active and passive processes, b) there is a small secretion of endogenous HCO3-, c) alkaline secretion is electrogenic, d) Cl- does not contribute to the short-circuit current, e) alkaline secretion is partially dependent on nutrient Na+ that acts in a facilitatory, not cotransport, role, f) there is no Cl--HCO3- exchange, and g) alkaline secretion is independent of nutrient pH.
Effects of luminal nutrition and metabolic status on in vivo glucose absorption
Authors: Kotler D. P. , Levine G. M. , Shiau Y. F.
Published: December 2017

Luminal nutrients, but not metabolic status, maintain active glucose transport by the rat intestine in vitro. The present study was designed to examine the effects of these factors on the in vivo absorption of glucose and 3-O-methylglucose. Rats were fed either intraluminally or by total parenteral nutrition (TPN) for 7 days or fasted for 72 h. Sugar absorption was measured under pentobarbital sodium (Nembutal) anesthesia at concentrations from 7 to 28 mM. Luminally fed rats had a significantly greater mucosal mass and absorption rates per centimeter of both sugars than either TPN or fasted animals. However, TPN rats had significantly greater absorption per milligram protein (i.e., specific activity) for both glucose and 3-O-methylglucose than luminally fed rats. In addition, TPN rats absorbed significantly more glucose per milligram protein, but not 3-O-methylglucose, than fasted animals. These data indicate: 1) luminal nutrients maintain glucose absorption by their trophic effects on mucosal mass; 2) the increase in specific activity for sugar absorption after TPN is unrelated to caloric balance; and 3) intestinal glucose metabolism affects its rate of absorption of glucose, but not 3-O-methylglucose.
Interaction of hydrocortisone and caerulein on pancreatic size and composition in the rat
Authors: Morisset J. , Jolicoeur L. , Genik P. , Lord A.
Published: December 2017

To determine the effects of hydrocortisone and caerulein (separately and in combination) on the exocrine pancreas of suckling, recently weaned, growing, and adult rats, we administered hydrocortisone (0.5 mg/100 g body wt), caerulein (1 microgram/kg), and a combination of these two hormones for 3 days. The rats were killed, and the pancreas was weighed and analyzed for DNA, protein, amylase, and chymotrypsinogen. Caerulein alone was associated with significant decreases in amylase, chymotrypsinogen, and protein concentration in suckling rats; after weaning, it produced significant increases of these same parameters, representative of pancreatic hypertrophy. Hydrocortisone caused significant increases in DNA content and enzyme and protein concentrations in suckling rats; after weaning, the steroid significantly decreased DNA content in 26-day-old rats, but increases in enzyme and protein concentration were observed. Using an increase in DNA content as an index of hyperplasia and cellular mass and enzyme and protein concentrations as indices of hypertrophy, we conclude that over a 3-day period 1) caerulein produced pancreatic hypertrophy after weaning while potentiating the hyperplastic and hypertrophic action of hydrocortisone in suckling rats; and 2) hydrocortisone potentiated the hypertrophic effect of caerulein after weaning. The data suggest that these two hormones may regulate acinar cell proliferation and enzyme synthesis of the exocrine pancreas.
Study of the possible enteropancreatic circulation of pancreatic amylase in the dog
Authors: Levitt M. D. , Ellis C. J. , Murphy S. M. , Schwartz M. L.
Published: December 2017

The possible existence of an enteropancreatic circulation of amylase was investigated in the dog. Endogenous amylase concentration in pancreatic venous blood was consistently greater than that in arterial blood, indicating a net flux of amylase from the pancreas to blood. Less than 0.02% of the metabolic clearance of 125I-amylase was accounted for by 125I-amylase in pancreatic secretions, indicating a minimal flux of amylase from the blood to pancreatic secretions. The venous-arterial amylase concentration across gut segments containing large quantities of amylase was not significantly different from 1.00, indicating absorption of less than 0.2% of the luminal amylase per hour. No 125I-amylase was detectable in serum after endoscopic instillation of labeled enzyme into the duodenum. These studies demonstrate negligible intestinal absorption of amylase and negligible pancreatic extraction of amylase, indicating negligible enteropancreatic circulation of pancreatic amylase in the dog.
Studies on the inhibition of pancreatic secretion by luminal somatostatin
Authors: Konturek S. J. , Tasler J. , Cieszkowski M. , Jaworek J. , Arimura A. , Schally A. V.
Published: December 2017

The effects of somatostatin, instilled into the duodenum or administered intravenously, on pancreatic response to endogenous (meal and duodenal acidification) or exogenous (secretin and caerulein) stimulants were compared in five dogs with gastric and pancreatic fistulas. Somatostatin, whether applied topically to the duodenal mucosa or given intravenously, resulted in qualitatively similar inhibition of pancreatic secretion of water, bicarbonate, and enzyme protein, being about four to eight times less potent after intraduodenal than after intravenous administration. A meal-induced secretion appears to be the most sensitive to the inhibitory action of intraduodenal somatostatin, probably because of the suppression of gastric acid and serum gastrin secretin involved in the postprandial stimulation of the exocrine pancreas. The inhibition of pancreatic secretion by luminal somatostatin was accompanied by a significant increase of plasma levels of the immunoreactive somatostatin, indicating that this peptide can be absorbed intact across the intestinal mucosa. We conclude that somatostatin administered into the gut lumen is absorbed into the circulation and can inhibit pancreatic secretion both by the suppression of the release of gastrointestinal hormones and by direct inhibitory action on the exocrine pancreas.
Duodenogastric reflux in the fasting dog: role of pylorus and duodenal motility
Authors: Muller-Lissner S. A. , Schattenmann G. , Schenker G. , Sonnenberg A. , Hollinger A. , Siewert J. R. , Blum A. L.
Published: December 2017

A two-marker technique was used to determine duodenogastric reflux in fasting dogs with normal or surgically modified gastroduodenal junctions. All nine dogs had an esophagostomy for gastric marker perfusion. The duodenal marker was given via a duodenal fistula. In two dogs a Heineke-Mikulicz pyloroplasty was performed, and in four dogs extramucosal circular pylorectomy was performed in addition. The mean fasting duodenogastric reflux rate in dogs with a normal pylorus was 1.1 +/- 0.5 (SE) ml/10 min; after pyloroplasty it was 1.6 +/- 0.3 ml/10 min (P greater than 0.1), and after pylorectomy it was 1.5 +/- 0.4 ml/10 min (P greater than 0.1). Simultaneous intraduodenal manometry revealed no relation between the interdigestive myoelectric complex and reflux. The marker technique for the measurement of reflux was validated by pharmacologically induced reflux. Subcutaneous injection of 0.1 mg of apomorphine increased the reflux rate tenfold. A transpyloric tube increased reflux rate fivefold. It is concluded that, in the fasting dog, phenomena such as retropulsive peristalsis are determinants of duodenogastric reflux and not the presence or absence of the pylorus and normal interdigestive motility.
Effect of ethanol on amino acid absorption across in vivo rat intestine
Authors: Green R. S. , MacDermid R. G. , Scheig R. L. , Hajjar J. J.
Published: December 2017

The acute effect of ethanol on amino acid absorption across the in vivo rat intestine was studied using single-pass continuous perfusion and recirculation techniques. The single-pass steady-state perfusion was used to examine the effect on the entire small intestine and recirculation perfusion to examine the effect on short intestinal segments and to limit ethanol absorption. Unlike the in vitro findings of other investigators, ethanol does not cause inhibition of net amino acid absorption in vivo unless the alcohol is perfused in 2 M or higher concentrations. The inhibition that is observed at these concentrations is very likely due to severe injury and shedding of intestinal cells as evidenced by an increased recovery of DNA in the perfusates. The findings suggest that acute ethanol administration, in concentrations that are comparable to those found in the upper intestines of humans after the ingestion of moderate doses of alcohol, does not have a prominent effect on amino acid absorption across the in situ rat intestine. Under these conditions, the ethanol inhibition of active absorption is masked by enhanced diffusion of the amino acids across the intestine.
Pancreatic calcification: formation constants of CaHCO3+ and CaC03(0) complexes determined with Ca2+ electrode
Authors: Moore E. W. , Verine H. J.
Published: December 2017

Pancreatic calcification is a frequent complication of chronic pancreatitis, and pancreatic stones (95% CaCO3 as calcite) are observed in both humans and cattle, but little is known about the complex equilibriums governing calcium solubility. Using the Ca2+ electrode and equilibrium dialysis of NaHCO3-CaCl2-NaCl solutions (24 +/- 2 degrees C; total ionic strength = 0.153-0.161), studies were made at variable pH and total calcium and carbonate concentrations to determine the formation constants of the three possible calcium complexes: CaHCO3+, CaC03(0), and Ca(HCO3)20. If the first two complexes were present, a plot of ([Ca]/[Ca2+]-1)/[HCO3-] against the ionic ratio [C03(2)-]/[HCO3-] should be linear with intercept of the CaHCO3+ formation constant (K'aB) and slope of the CaC03(0) formation constant (K'aC). This was found to be the case in both dialysands and dialysates, using two different methods ("pH" and "K'sp") for estimation of [CO32-] values. Two other methods of data analysis were also used: simultaneous equations and multiple linear regression by matrix analysis. For all three methods, mean K'aB = 12.48 and mean K'aC = 1,870. There was no evidence for a Ca(HCO3)2(0) complex. We conclude that CaHCO3+ and CaC03(0) complexes may account for a substantial fraction of total soluble calcium is pancreatic juice. These studies provide a necessary step toward the construction of a quantitative physicochemical model of pancreatic calcium solubility.
Histamine receptor in bullfrog gastric mucosa
Authors: Hersey S. J.
Published: December 2017

The histamine receptor of isolated bullfrog gastric mucosa was characterized in terms of respiration and acid secretory responses to histamine antagonists and agonists. Cimetidine, a selective H2-antagonist, showed competitive antagonism of histamine responses with a pA2 value of 6.55. In contrast, the H1-antagonist, mepyramine, showed inhibition only at very high concentrations. Based on these results, the histamine receptor would be classified as the H2 type. Measurements of agonist potency sequence revealed a marked difference between the amphibian and mammalian gastric histamine receptors. The selective H1-agonists, 2-pyridylethylamine and 2-aminoethylthiozol, were found to be more efficacious than the selective H2-agonists, dimaprit and impromidine. The lack of efficacy for dimaprit and impromidine does not appear to be due to a lack of binding to the receptor because these agents inhibit responses to histamine. For dimaprit, the inhibition was found to be competitive with an apparent pA2 value of 5.37. These results indicate that there is a molecular difference between H2-receptors in mammals versus amphibians.
Stimulation of gastrin and somatostatin secretion from the isolated rat stomach by bombesin
Authors: DuVal J. W. , Saffouri B. , Weir G. C. , Walsh J. H. , Arimura A. , Makhlouf G. M.
Published: December 2017

The role of bombesin in the regulation of gastrin and somatostatin secretion was examined using an isolated vascularly perfused rat stomach preparation. Bombesin caused a biphasic, dose-dependent increase in gastrin and bombesin secretion. Neither somatostatin nor gastrin secretion was inhibited by atropine. The maximal gastrin response to bombesin (198 +/- 75% above basal levels) was less than one-half the maximal response to methacholine (462 +/- 94%). It was postulated that the concomitant release of somatostatin, in part from antral mucosa, attenuated the gastrin response to bombesin; the notion was tested with somatostatin antiserum. A 50- to 100-fold excess of sheep somatostatin antiserum augmented significantly the maximal gastrin response to bombesin by 966% in the initial peak period and by 532% in the plateau period; the response in the plateau period was not significantly different from the maximal response to methacholine. Methacholine stimulated the release of gastric bombesin also, but the exact cellular origin of the peptide could not be ascertained. On the basis of these results and of the topography of antral bombesin neurons and somatostatin D cells, a model for the neural (via bombesin) and paracrine (via somatostatin) control of gastrin secretion within the antrum is proposed.
Barrier function of epithelia
Authors: Powell D. W.
Published: December 2017

The ability of an epithelium to prevent permeation of noxious agents has not been well studied except in the gastrointestinal tract where exclusion of H+ has clinical significance. This article reviews the permeation routes across epithelia both as elucidated in the extensive electrophysiological work done in recent years and as demonstrated in morphological studies. We thus place concepts about gastrointestinal barrier function into the framework of transport physiology. Both the permeability and permselectivity of epithelial barriers are reviewed here. The effects of physical agents (pressure and electric current), polyvalent cations, organic compounds with both specific (channel blocking) and nonspecific (detergent) membrane properties, cyclic nucleotides, microfilament-active agents, and particularly H+ on both the barrier function (permeability and permselectivity) and transport function of epithelia are considered. Based on the available data, an important role for active Na+ transport in the maintenance of the epithelial barrier function can be postulated.
Intrinsic factor-mediated intestinal absorption of cobalamin in the dog
Authors: Marcoullis G. , Rothenberg S. P.
Published: December 2017

The purpose of these studies was to determine whether gastric intrinsic factor and the ileal intrinsic factor receptor participate in the process of cobalamin absorption in the dog. Physicochemical analysis of gastrointestinal fluids and mucosal extracts obtained 3-5 h after cyano[57Co]-cobalamin was fed to dogs demonstrated that 1) all cyano-[57Co]cobalamin became bound to proteins during intraluminal transport; and 2) mucosal cyano[57Co]cobalamin in the extract of the ileal mucosa was bound to intrinsic factor, to intrinsic factor coupled to receptor protein, and to proteins with properties similar to R protein and transcobalamin II. A significant fraction of the cyano[57Co]cobalamin in the mucosal extract was membrane bound and, upon solubilization with Triton X-100, was found to contain immunoreactive intrinsic factor that, however, could no longer couple to the isolated receptor. The formation of the complex of cobalamin with intrinsic factor and the receptor protein and the selective accumulation of cobalamin in the ileum indicate that the intrinsic factor-mediated mechanism for absorption of this vitamin is active in the dog.
Differential effect of glucocorticoids on structure and function of adult rat jejunum
Authors: Scott J. , Batt R. M. , Maddison Y. E. , Peters T. J.
Published: December 2017

The long-term (28 days) effects of feeding two glucocorticoids, prednisolone and betamethasone 17-valerate, on the adult rat jejunum were examined. Both steroids increased the activities of microvillus enzymes, alpha-glucosidase, aminopeptidase, and gamma-glutamyltransferase, measured in isolated epithelial cells by 46-83%. However, betamethasone 17-valerate caused striking epithelial hypoplasia such that microvillus enzyme activity per centimeter of intestine was similar to that of control rats. Prednisolone produced a trivial epithelial hypoplasia, and therefore microvillus enzyme activity per centimeter of intestine was increased. D-Galactose absorption measured in vivo was similarly affected by the two steroids. D-Galactose absorption per centimeter of intestine was increased after prednisolone but unchanged after betamethasone 17-valerate. Thus, glucocorticoids have separate and opposing actions on the function and structure of the adult rat small intestine: a) to increase the digestive-absorptive function of the mature epithelial cell and b) to decrease the epithelial cell population. These findings suggest that the effect of any particular glucocorticoid on intestinal function will depend on the extent to which these opposing actions predominate.
Prostaglandin E2-binding sites and cAMP production in porcine fundic mucosa
Authors: Tepperman B. L. , Soper B. D.
Published: December 2017

Biologically active [3H]prostaglandin E2 (PGE2) bound rapidly and specifically to membrane fractions from hog fundic mucosa. Optimal binding occurred in the 30,000-g membrane preparation at 37 degrees C (pH 5.0). Scatchard analysis of specific PgE2 binding revealed the presence of a heterogeneous population of binding sites with Kd values and binding site concentrations of approximately 1 X 10(-9) M and 1 fmol/mg prot and 2 X 10(-8) M and 20 fmol/mg prot, respectively. Specific binding was inhibited by the following agents in descending order of potency: PGE1, PGA2, PGD2, 6-keto-PGF1 alpha, and thromboxane B2. Trypsin treatment or boiling reduced or abolished specific PGE2 binding. PGE2 stimulated cAMP formation in the 2,500-g fraction, with an approximate Km of 1 X 10(-6) M, but stimulation of adenylate cyclase activity by PG was not evident in the 16,000-g or 30,000-g tissue preparations. These results suggest that a specific PGE2-binding site exists in the 16,000-g and 30,000-g fractions of porcine fundic mucosa, although an increase in cAMP-forming capacity could not b of 1 X 10(-6) M, but stimulation of adenylate cyclase activity by PG was not evident in the 16,000-g or 30,000-g tissue preparations. These results suggest that a specific PGE2-binding site exists in the 16,000-g and 30,000-g fractions of porcine fundic mucosa, although an increase in cAMP-forming capacity could not b of 1 X 10(-6) M, but stimulation of adenylate cyclase activity by PG was not evident in the 16,000-g or 30,000-g tissue preparations. These results suggest that a specific PGE2-binding site exists in the 16,000-g and 30,000-g fractions of porcine fundic mucosa, although an increase in cAMP-forming capacity could not be localized in these fractions in vitro.
Ultrastructural changes related to functional activity in gastric oxyntic cells
Authors: Forte J. G. , Black J. A. , Forte T. M. , Machen T. E. , Wolosin J. M.
Published: December 2017

When stimulated to secrete HCl the gastric oxyntic cell undergoes profound morphological change. The identifiable apical cell surface is greatly expanded in the stimulated oxyntic cell as compared with nonsecreting ones. To account for this change, one hypothesis proposes that the expanded surface is derived from the fusion of cytoplasmic tubulovesicular membranes with the existing limited apical membrane surface. An alternative hypothesis suggests that the tubulovesicular compartment is actually confluent with the apical surface at all times and that the morphological appearance follows the expansion of this supercollapsed compartment as HCl secretion commences. A variety of morphological evidence is reviewed here including transmission electron microscopy during various stages of secretion and inhibition, analysis of freeze-fracture replicas, penetration of macromolecular tracers, and membrane surface-staining characteristics. It is concluded that the weight of evidence favors a membrane fusion process. Moreover, recent comparative studies of membrane fractions from resting and secreting stomachs show different morphological and functional properties that are also consistent with a fusion hypothesis as a fundamental event in the membrane transformation of the oxyntic cell.
Conservation of mannitol, lactulose, and raffinose by the human colon
Authors: Saunders D. R. , Wiggins H. S.
Published: December 2017

We measured fecal composition after giving oral doses of mannitol, lactulose, or raffinose to ileostomy patients and to normal subjects in order to determine the colon's capacity for metabolizing these carbohydrates and to decide whether volatile fatty acids (VFA) or unabsorbed carbohydrate initiated diarrhea. Seventy-four percent of mannitol, 100% of lactulose, and 88% of raffinose passed unabsorbed through the small intestine of six patients with ileostomies. Dose-response experiments revealed that normal subjects could tolerate 120-220 mmol of mannitol, 73-146 mmol of lactulose, or 80 mmol of raffinose before fecal output of water exceeded 400 ml in 48 h or before test carbohydrate appeared in the stool. Mannitol could be metabolized to glucose; lactulose to fructose, galactose, and glucose; and raffinose to sucrose, melibiose, fructose, galactose, and glucose. The output of VFA in fecal water did not correlate with the moles of carbohydrate metabolized, and it did not greatly exceed the output of VFA in stools of equal volume that were induced by nonfermentable MgSO4. We conclude that the human colon is capable of removing appreciable amounts of single doses of these carbohydrates from fecal water. When this capacity is exceeded, unabsorbed carbohydrate rather than VFA prompts an increased output of fecal water.
Release of [3H]norepinephrine from nerves in rat colonic mucosa: effects of norepinephrine and prostaglandin E2
Authors: Wu Z. C. , Gaginella T. S.
Published: December 2017

Release of [3H]norepinephrine ([3H]NE) from noradrenergic nerves innervating rat colonic mucosa was studied by superfusion of a muscle-stripped preparation of rat colon. After a period of incubation with [3H]NE, the tissue was superfused with different releasing agents. Depolarization of the tissue with a medium containing 50 mM K+ evoked the release of [3H]NE. Veratridine (5 X 10(-5) M) also stimulated the efflux of [3H]NE; this was blocked by tetrodotoxin (2 X 10(-7) M). Tyramine, which releases NE by a nondepolarizing mechanism, also evoked [3H]NE release from the colonic mucosal preparation, and this release was not decreased in the absence of calcium. Exogenous NE (10(-7) M) inhibited the high K+-evoked release by 50% in the presence of desmethylimipramine, a NE uptake inhibitor. In addition, prostaglandin E2 (1 X 10(-7) M) significantly reduced the K+-evoked release to less than 50% of control. Pretreatment with 6-hydroxydopamine, which selectively destroys NE neurons, reduced the K+-evoked release of [3H]NE to 40% of control. This study suggests that colonic mucosa of the rat contains noradrenergic nerves that function in a manner characteristic of the noradrenergic nerves in other tissues.
Effect of fat feeding on intestinal alkaline phosphatase activity in tissue and serum
Authors: Young G. P. , Friedman S. , Yedlin S. T. , Allers D. H.
Published: December 2017

Serum intestinal alkaline phosphatase activity is increased by fat feeding, but the mechanism of this increase is not fully understood. Fasting rats were fed a single feed of either corn oil (12 kcal) or an isocaloric elemental feed (Vivonex 100 HN). Changes in enzyme activity in the small bowel mucosa and serum were followed for 20 h. Only the fat-fed rats had increased serum enzyme activity, being maximal at 7 h and three times the fasting level. This resulted from an increase in the amount of enzyme protein in the serum and not from an increase in its catalytic efficiency. The serum biological half-life of 125I-labeled intestinal alkaline phosphatase was the same in fasted (2.51 min) and fat-fed rats (2.55 min). Both types of feed caused a quantitatively similar increase in brush-border-bound alkaline phosphatase activity. However, levels of soluble intracellular alkaline phosphatase in intestinal mucosa were affected differently: the elemental diet caused a substantial rise, whereas no significant change was seen after fat feeding. The isoelectric pattern of phosphatase activity in serum after fat feeding was identical to that of soluble intracellular and not membranous alkaline phosphatase. Therefore, serum intestinal alkaline phosphatase activity rises in response to a single fat feed as a result of increased delivery of the enzyme to the blood and not as a result of an increase in its normally short biological half-life. This rise cannot be directly linked to an increase in the amount of brush-border-bound enzyme, and it appears that the serum enzyme is derived directly from a pool of soluble intracellular enzyme in the small bowel mucosa.
A new animal model for studies of in vivo folate kinetics
Authors: Steinberg S. E. , Campbell C. , Hillman R. S.
Published: December 2017

Characterization of transport kinetics involved in tissue folate supply has been limited by the inability to accurately measure the uptake and metabolism of folate by rapidly proliferating tissues. The present report describes a new animal model that uses subcutaneous fibrosarcoma implants as a target tissue for studies of folate supply. The fibrosarcoma grows rapidly as a well-encapsulated, nonmetastasizing nodule(s) and does not disrupt the animal's normal growth and nutrition. Moreover, the tumor nodules avidly take up labeled folate and can be removed easily by local excision for measurements of uptake and intracellular metabolism of folate.
Calcium transport in the ileum of uremic rats
Authors: Koller M. , Binswanger U.
Published: December 2017

Duodenal and ileal calcium transport was studied by 45Ca uptake and estimation of unidirectional fluxes in vitro in kidney-intact and 5/6-nephrectomized rats. After normal-calcium diet, calcium transport was impaired by uremia in the duodenum but not in the ileum. However, 5/6-nephrectomized rats on low-calcium diet showed, in concert with impaired growth, a reduced calcium transport both in duodenum and ileum. Comparing data after normal- and low-calcium diets, the ileal adaptation to low-calcium diet was intact in mild renal failure but abolished in severe uremia (urea less than 100 mg/dl). These results suggest that ileal calcium transport after normal-calcium diet is mainly passive. Taking into account reduced food intake as an additional factor, the active ileal calcium transport after low-calcium diet declines with progressive renal failure according to decreasing levels of 1,25-dihydroxyvitamin D3. A suspected enhancement of the distal small intestinal calcium transport by parathyroid hormone in uremic rats as compensation for proximally impaired absorption could not be demonstrated.
Prostaglandin synthesis inhibition and postprandial intestinal hyperemia
Authors: Gallavan R. H. , Chou C. C.
Published: December 2017

The effect of prostaglandin synthesis inhibition on the postprandial intestinal hyperemia was examined in the jejunum of anesthetized dogs. Both intravenous and intra-arterial infusion of the cyclooxygenase inhibitors indomethacin and mefenamic acid reduced resting jejunal blood flow and markedly enhanced the food-induced jejunal hyperemia. The jejunal vascular response to food did not change after either intravenous or intra-arterial infusion of the carrier solutions or intra-arterial infusion of angiotensin II. The enhancement of the jejunal hyperemia was associated with an increase in the food-induced increase in jejunal oxygen consumption. Infusion of the cyclooxygenase inhibitors increased the mean amplitude of the monophasic intestinal contractions; however, this did not appear to play a role in the enhancement of the food-induced hyperemia. The study indicates that inhibition of prostaglandin synthesis has a marked effect on the postprandial intestinal hyperemia and that this may be due to its enhancement of the jejunal metabolic response to food. The prostaglandins involved and their mechanism of action are unknown.
Stimulation of gastric acid secreted by glycine and related oligopeptides in humans
Authors: Wald A. , Adibi S. A.
Published: December 2017

To investigate the effect of oligopeptides on gastric secretion in humans, we investigated acid secretion in healthy volunteers after the intragastric infusion of physiological saline, glycine (100 mM), diglycine (50 mM), triglycine (33 mM), and tetraglycine (25 mM). All test solutions were equivalent in glycine content, osmolality (300 mosmol), and pH (5.5). Although the rate of acid secretion was greater during glycine than saline infusion [5.6 +/- 0.8 vs. 3.3 +/- 1.1 mmol/h (means +/- SE); P less than 0.05], the rate of acid secretion during glycine infusion was not significantly different from that induced by its related peptides. There were increases in plasma glycine concentration during infusion of glycine and its related peptides but no detectable changes in serum gastrin levels. The increases in plasma glycine must have been due to absorption from the small intestine because there was no gastric absorption of glycine in free or dipeptide form nor diglycine hydrolysis in the stomach. Therefore, our results permit implicating only the increased plasma glycine concentrations as the stimulus for acid secretion by glycine and its homologous peptides.
In vitro stimulation of cell growth by hepatic stimulator substance
Authors: LaBrecque D. R.
Published: December 2017

An extract of normal weanling or adult regenerating rat liver called hepatic stimulator substance (HSS) stimulates incorporation of tritiated thymidine ([3H]dThd) into liver DNA. In vivo, it is organ specific, species nonspecific, displays diurnal rhythm, and has a molecular weight of approximately 10,000-20,000. It has now been further characterized in vitro. HSS retained organ specificity, stimulating normal adult hepatocytes in primary culture, the HTC, PLC, and MH1C1 hepatoma cell lines, and the PRC rat liver cell line. It did not stimulate human or mouse lymphocytes, 3T3 mouse fibroblasts, Y1BS1 mouse adrenal cells, Chinese hamster ovary cells, rat hypernephroma cells, C6 rat glial cells, or L1210 mouse leukemic cells. More detailed studies of the response of HTC cells to HSS revealed a dose-dependent increase in [3H]dThd incorporation (up to 30-fold) with a response to as little as 140-ng purified extract/ml culture medium. Autoradiography confirmed that the thymidine was taken up by nuclear DNA. This represented a true stimulation of growth as shown by an almost twofold increase in cell number after 6 days of exposure to low doses of HSS.
Pancreatic effects of ethionine: blockade of exocytosis and appearance of crinophagy and autophagy precede cellular necrosis
Authors: Koike H. , Steer M. L. , Meldolesi J.
Published: December 2017

Young female mice fed a choline-deficient, ethionine-supplemented (CDE) diet for 24 h develop hemorrhagic pancreatic necrosis with a 5-day mortality rate of approximately 50%. At the end of the diet administration, the in vivo discharge of digestive enzymes is blocked, images of exocytosis and luminal membrane recycling disappear, and zymogen granules accumulate within acinar cells. The general ultrastructure, however, remains well preserved, protein synthesis is normal, and intracellular transport of secretory proteins is only slightly retarded. Thus, the CDE diet does not affect the general phenomenon of membrane fusion-fission but specifically inhibits that associated with exocytosis. Twenty-four hours after withdrawal of the CDE diet, discharge of zymogen granules into lysosomes (crinophagy) can be observed, and, 24 h latr, autophagocytosis is noted. Finally, shortly before the onset of pancreatic necrosis, cells of nearly normal appearance are noted to be scattered among cells showing varying degrees of lesion up to complete disruption. Thus, the CDE-induced pancreatic necrosis results from a sequence of events: blockade of exocytosis evolves to crinophagy and autophagy, which might lead to lysosomal activation of zymogens.
Postreceptor modulation of action of VIP and secretin on pancreatic enzyme secretion by secretagogues that mobilize cellular calcium
Authors: Collen M. J. , Sutliff V. E. , Pan G. Z. , Gardner J. D.
Published: December 2017

In dispersed acini from rat pancreas, secretagogues that act through or mimic the action of AMP [vasoactive intestinal peptide (VIP), secretin, or 8-bromo-AMP] caused a twofold increase in amylase secretion. Secretagogues that mobilize cellular calcium (carbamylcholine, C-terminal octapeptide of cholecystokinin, bombesin, or A23187) caused a sevenfold augmentation of the actions of VIP, secretin, or 8-bromo-cAMP on enzyme secretion. Carbamylcholine and the C-terminal octapeptide of cholecystokinin also augmented the action of VIP on amylase secretion from mouse pancreatic acini. Secretagogues that mobilize cellular calcium did not alter binding of 125I-VIP, cellular cAMP, or the increase in cellular cAMP caused by VIP or secretin. Similarly, secretagogues that increase cellular cAMP did not alter 45Ca outflux or the increase in 45Ca outflux caused by carbamylcholine, C-terminal octapeptide of cholecystokinin, bombesin, or A23187. These results indicate that in dispersed acini from rat pancreas there is postreceptor modulation of the actions of VIP and secretin on enzyme secretion by secretagogues that mobilize cellular calcium and that this modulation is a major determinant of the magnitude of the effect of VIP and secretin on enzyme secretion. This modulation, in turn, reflects the ability of cellular calcium, mobilized from intracellular stores, to amplify the action of cellular cAMP on the enzyme secretory process.
Effects of ischemia and oxygen radicals on mucosal albumin clearance in intestine
Authors: Grogaard B. , Parks D. A. , Granger D. N. , McCord J. M. , Forsberg J. O.
Published: December 2017

Mucosal albumin clearance was measured in jejunal segments of dogs under control conditions, after arterial occlusions of varying duration (15 min-4 h), and during intraluminal perfusion with hypoxanthine-xanthine oxidase. Albumin clearance rates were estimated from the luminal perfusion rate and the activity of protein-bound 125I in the perfusate and plasma. Arterial occlusion of 30-min to 4-h duration produced a significant increase in mucosal albumin clearance. The magnitude of the rise in albumin clearance was directly related to the duration of arterial occlusion. Pretreatment with superoxide dismutase, a superoxide radical scavenger, or allopurinol, a xanthine oxidase inhibitor, did not prevent the increased albumin clearance induced by 1 h of occlusion. Intraluminal perfusion with hypoxanthine-xanthine oxidase significantly increased mucosal albumin clearances. This increase was prevented by superoxide dismutase. The results of this study indicate that arterial occlusions and enzymatically generated superoxide radicals increase mucosal albumin clearance.
A model of the mesenteric circulation
Authors: Jacobson E. D. , Gallavan R. H. , Fondacaro J. D.
Published: December 2017

A model of the mesenteric microcirculation is proposed that explains three observed variations in the hyperemic response of the small intestine to different dilator stimuli. The model assumes a two-component circulation in which one component delivers more than enough blood flow and oxygen to meet the metabolic demands of the resting tissue served by this "flow-independent component." The second portion, known as the "flow-limited component" delivers an insufficient blood supply for tissue needs and, therefore, restricts the metabolism of the parenchyma it serves. The three types of reported hyperemic responses are a) hyperemia induced by certain drugs, such as nifedipine and acetylcholine, in which case only the flow-limited component is dilated and one observes an increase in blood flow to the gut without any increase in intestinal oxygen consumption; b) hyperemia induced by stimulating active cotransport of nutrients from the intestinal lumen, in which case the tissue served by the flow-independent component increases its metabolism and oxygen demand, resulting in an increase in oxygen consumption that exceeds proportionately the increase in blood flow; and c) hyperemia induced by other vasodilator drugs, such as adenosine, in which case both vascular components are dilated and both blood flow and oxygen uptake are increased, but the increase in blood flow is proportionately greater than the increase in oxygen consumption.
Duodenogastric reflux in the dog
Authors: Sonnenberg A. , Muller-Lissner S. A. , Schattenmann G. , Siewert J. R. , Blum A. L.
Published: December 2017

Duodenogastric reflux, gastric emptying, and gastric secretion were measured simultaneously by a double-marker technique after instillation of a liquid lipid meal (300 ml Intralipid) or a protein meal (300 ml Bactopeptone) in five trained mongrel dogs. A lipid meal was emptied slower and elicited less volume secretion than a protein meal. Duodenogastric reflux rate and intragastric accumulation of duodenal contents were similar with both meals. Intravenous infusion of atropine slowed gastric emptying and inhibited gastric volume secretion only in the case of protein meal. Atropine increased duodenogastric reflux rate and gastric accumulation of duodenal contents with both protein and lipid meals. The percentage of duodenal contents inside the stomach increased continuously during gastric emptying; it did not exceed 20% with both meals given alone and 40% with both meals given together with atropine. It is concluded that duodenogastric reflux and gastric accumulation of duodenal contents are common phenomena during gastric digestion of a meal. The degree of such accumulation does not depend on the type of meal. Intragastric accumulation of duodenal contents is increased when duodenogastric reflux rate is stimulated and when gastric emptying rate is inhibited simultaneously.
Continuous measurement of intestinal mucosal blood flow by laser-Doppler velocimetry
Authors: Shepherd A. P. , Riedel G. L.
Published: December 2017

To measure blood flow in the intestinal mucosa we built a laser-Doppler flowmeter that consists of a helium-neon laser, an electronic circuit, and a pair of fiber-optic light guides that conduct laser light to the tissue and carry the backscattered light to a photodetector. Because light scattered by moving red blood cells experiences a shift in its frequency, we measured blood flow by detecting the mean Doppler frequency. In isolated loops of canine small bowel, we raised perfusion pressure and found the increases in laser mucosal blood flow were significantly correlated with total blood flow measured by an electromagnetic probe. During infusions of isoproterenol (a selective vasodilator of the mucosa), laser mucosal blood flow increased before total flow increased. Similarly, adenosine (a selective dilator of the muscularis) increased total flow, whereas local mucosal blood flow fell or was unchanged. In addition, reactive hyperemia was sometimes observed in the mucosa but not in the muscularis. These observations indicate that the laser-Doppler technique measures blood flow in the surface tissue and does not reflect blood flow throughout the other tissues of the bowel wall. Instrumental problems identified in this study were 1) the difficulty of calibrating the laser mucosal blood flowmeter in absolute units, 2) the uncertainty of the volume of tissue in which local mucosal blood flow is measured, and 3) the problem of maintaining contact between the optical probe and the tissue. Nevertheless, the method holds great promise because it can detect small ischemic areas, because it could be used in combination with endoscopy, and because it yields a continuous measurement of blood flow in either the muscularis or mucosa.
Hepatobiliary and pancreatic clearance of circulating pancreatic amylase
Authors: Rosenblum J. L. , Raab B. K. , Alpers D. H.
Published: December 2017

The hepatobiliary and pancreatic uptake of pancreatic amylase was studied in the conscious rabbit. Four hours after intra-arterial injection of 125I-labeled porcine or rabbit pancreatic amylase, about 7% of the administered radioactive dose appeared in liver and bile, but less than 0.2% appeared in the pancreas and pancreatic juice. No amylolytic activity was detectable in bile, but a significant fraction of the acid-precipitable radioactive counts in bile comigrated with the injected amylase on gel autoradiography. Enzymatic activity appeared in bile after continuous intraarterial infusion of pancreatic amylase with excellent correlation between biliary and plasma amylase activities (r greater than or equal to 0.94). Only a small percentage (0.002%) of amylase delivered to liver, however, was excreted into bile. After intraduodenal instillation of radiolabeled pancreatic amylase or ribonuclease A, virtually none of the radioactivity appeared in the pancreas, and none in bile was acid precipitable. We conclude that a small but definite amount of the circulating pancreatic amylase is excreted intact into bile in the conscious rabbit. There is, however, no significant enterohepatic or enteropancreatic circulation of pancreatic enzymes.
Effect of changes in circulating amylase levels on amylase output in bile
Authors: Grendell J. H. , Rothman S. S.
Published: December 2017

The relation between plasma and biliary amylase activity and their relationship to the functional state of the pancreas were studied in anesthetized rabbits. Repetitive intravenous injections of cholecystokinin resulted in a 25-fold rise in the secretion of amylase via the pancreatic duct, followed at first by a 50% increase in plasma amylase concentration and later by a 270% increase in biliary amylase concentration. There was then a gradual, roughly synchronous decline in both plasma and biliary values toward basal level despite a continued highly augmented rate of pancreatic ductal secretion. "Near-total" pancreatectomy completely abolished the effect. These observations are consistent with a cholecystokinin-induced basolateral secretion of amylase from pancreas into blood and its subsequent movement from blood into bile down a concentration gradient. The output of amylase in bile, however, was quite small and does not suggest that biliary transport of amylase has an important function either as a means of secreting and recycling digestive enzyme into the gut or as a major excretory pathway for circulating amylase in the rabbit.
Effects of bicarbonate and pH on chloride transport by gastric mucosa
Authors: Manning E. C. , Machen T. E.
Published: December 2017

HCO3 and pH dependence of net Cl transport (JClnet) by resting (metiamide-treated) frog gastric mucosa has been investigated in vitro by measuring short-circuit current (Isc = JClnet) and transepithelial conductance (G). With either 100% O2 or 95% O2-5% CO2 gassing, HCO3-free solutions caused large (greater than 50%) reductions in Isc and G. Increases in [HCO3] of the serosal, but not mucosal, solution caused increases in Isc and G. At least part of the effect appeared to be due specifically to the HCO3 moiety, as opposed to the pH changes that also occurred. In HCO3-free solutions (100% O2), increasing serosal solution pH above 7 with either permeable or impermeable buffers caused Isc and G to increase; permeable buffers were somewhat more effective than impermeable buffers. Measurements of intracellular pH (pHc) with [14C]DMO or [14C]methylamine showed that increases in extracellular pH (pHo) caused increases in cellular pH (pHc), and these changes in pHc were independent of buffer type. We conclude that HCO3 and/or high pHo stimulate Isc and G and that buffer permeability and cellular concentration can also affect transport.
Selective modification of the ability of cholecystokinin to cause residual stimulation of pancreatic enzyme secretion
Authors: Villanueva M. L. , Martinez J. , Bodanszky M. , Collins S. M. , Jensen R. T. , Gardner J. D.
Published: December 2017

In the C-terminal heptapeptide of cholecystokinin (-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-Phe-NH2), replacing the aspartic acid residue by beta-aspartic acid did not alter the ability of the peptide to cause stimulation, desensitization, or residual stimulation of enzyme secretion from dispersed pancreatic acini. Replacing the tyrosine sulfate residue by hydroxynorleucine sulfate did not alter the ability of the heptapeptide to cause stimulation or desensitization, but caused a 50-fold decrease in the potency with which the peptide caused residual stimulation of enzyme secretion. These findings suggest that a modification of the N-terminal region of cholecystokinin heptapeptide, which does not alter the ability of the peptide to bind to its receptor on pancreatic acini and by so doing cause stimulation and desensitization of enzyme secretion, can increase the rate at which the bound peptide dissociates when the acini are washed and reincubated. This increased dissociation is reflected by a reduction in the potency with which the peptide causes residual stimulation of enzyme secretion.