bluuebunny/crossref_metadata_2025 huggingface dataset:
Gastric blood flow determination: intramural distribution and arteriovenous shunting of microspheres
Authors: Varhaug J. E. , Svanes K. , Svanes C. , Lekven J.
Published: December 2017

Total and regional gastric blood flows were measured in 23 anesthetized cats by labeled 10-micron (range 8-12 microns) and 15-micron (range 12-20 microns) microspheres. Total blood flow correlated closely with the gastric venous outflow. Flow estimates by 10-microns spheres were 2.95% lower than simultaneous 15-micron estimates. Approximately 2% of the 10-micron spheres and 0.1% of the 15-micron spheres were shunted through the gastric vasculature. The diameter distribution of 6,245 embolized spheres, measured by microscopy, corresponded to that of the injectate, except for a lack of the smallest spheres. Within the mucosa, the 10-microns spheres predominantly lodged in the glandular layer, whereas larger spheres gradually lodged more basally; 50% of the 15-microns population appeared in the lamina propria below the gland bases. Vasodilation did not alter the intramucosal distribution. Spheres in the subglandular lamina propria represented blood flow mainly to the glandular layer. It is therefore essential for reliable estimation of blood flow to the glandular layer of the mucosa that the lamina propria is completely included in the specimens. The submucosa contained only 0.5% of the 10-microns and 2.2% of the 15-micron embolized spheres. Spheres of 10.5-17 microns in diameter are considered the most suitable for determination of gastric blood flow.
Localization of cholesterol synthesis in the small intestine of diabetic rats
Authors: Feingold K. R. , Moser A. H.
Published: December 2017

Previous studies have demonstrated that cholesterol synthesis is increased twofold in the small intestine of diabetic animals. The present study demonstrates that the stimulation of small intestinal cholesterol synthesis by diabetes is a generalized phenomenon occurring in all segments of the small intestine. Quantitatively, in control animals the proximal two segments of the small intestine account for the majority of the total small intestinal cholesterol synthesis, whereas in the diabetic animals, because of the generalized stimulation in cholesterogenesis, the contribution of the terminal segments to total small intestinal cholesterol synthesis is of increased importance. The various manipulations that regulate cholesterol synthesis in the small intestine of diabetic animals also affect cholesterol synthesis in all portions of the small intestine. In diabetic animals cholesterol feeding and the limitation of food intake decrease cholesterol synthesis in the total small intestine and in all segments of the small intestine. Conversely, colestipol feeding increases cholesterol synthesis in all segments of the small intestine. These results demonstrate that, despite the obvious structural, functional, and environmental differences among the various segments of the small intestine, the stimulation of cholesterol synthesis that occurs secondary to diabetes mellitus is a generalized phenomenon. Similarly, the factors that regulate small intestinal cholesterol synthesis do so in a generalized manner.
Age-related changes in colonic function in rats
Authors: McDougal J. N. , Miller M. S. , Burks T. F. , Kreulen D. L.
Published: December 2017

Aging in humans is associated with changes in gastrointestinal function. We wanted to determine whether a similar phenomenon occurs in rats and whether rats would be a suitable model to study changes in the gastrointestinal tract with age. Intestinal transit, response in vitro of circular colon strips to bethanechol and electrical stimulation, and colonic smooth muscle histology were compared for post-pubertal (5-12 mo) and senescent (25-28 mo) male Fischer 344 rats. Colonic transit of 51Cr was decreased 45% in senescent rats in comparison with younger rats. The maximum response of circularly oriented muscle strips from senescent rats to electrical stimulation of nerves was 32% less than the maximum response of strips from postpubertal rats. Likewise, the maximum response of the muscle strips to bethanechol was 16% less in the senescent group compared with the postpubertal group. There was no difference between the two groups in the EC50 of bethanechol. The thickness of the muscle layers and the percent circular muscle of strips fixed at optimum length were the same in both age groups. The senescent rat appears to be a useful model for the study of gastrointestinal changes with aging.
Release of somatostatinlike immunoreactivity from canine fundic mucosal cells in primary culture
Authors: Soll A. H. , Yamada T. , Park J. , Thomas L. P.
Published: December 2017

We have developed a model to allow study of the release of somatostatinlike immunoreactivity (SLI) from gastric mucosal cells. Collagenase-dispersed canine fundic mucosal cells were separated by counterflow elutriation. SLI-containing cells were identified in the fractions with small cells (9-11 microns), and these fractions were plated onto collagen. After 2 days in culture, SLI content of the cells was maintained; SLI-positive cells, detected by peroxidase-antiperoxidase immunohistochemistry, comprised 70 +/- 6% (mean +/- SE, n = 6) of these cultured cells. Release of SLI from these cultures into the medium was determined by radioimmunoassay. Epinephrine, dibutyryl cAMP, and gastrin each stimulated SLI release in a time-dependent manner, with a steady rate of secretion maintained for 120 min of incubation. Both epinephrine and dibutyryl cAMP markedly potentiated the release of SLI stimulated by gastrin but were not themselves mutually potentiating. Upon Sephadex G-50 column chromatography of incubation medium and extracts of cultured cells, SLI eluted primarily in a single peak that cochromatographed with synthetic somatostatin tetradecapeptide. Our data suggest that gastrin and adrenergic stimuli act directly on canine fundic somatostatin cells and that potentiating interactions between secretagogues may be important modulating elements in somatostatin cell secretory function.
Autonomic regulation of somatostatin release: studies with primary cultures of canine fundic mucosal cells
Authors: Yamada T. , Soll A. H. , Park J. , Elashoff J.
Published: December 2017

Using a newly developed system for culturing canine fundic mucosal cells, we examined regulation of the secretion of somatostatinlike immunoreactivity (SLI) by cholinergic and adrenergic transmitters. Enzyme-dispersed canine fundic mucosa cells were enriched in SLI content by counterflow elutriation and cultured on collagen for 42 h. Epinephrine alone, and in combination with gastrin, stimulated SLI secretion in a dose-dependent fashion. Propranolol did not alter the response to dibutyryl cAMP or gastrin but produced a parallel, rightward shift of the epinephrine dose-response curve with the dissociation constant (Ki) determined to be 14 nM by nonlinear curve fitting. Phentolamine, an alpha-adrenergic antagonist, enhanced SLI secretion in response to epinephrine, an effect reversed by the alpha 1-agonist methoxamine but not by the alpha 2-agonist clonidine. However, neither methoxamine nor clonidine alone inhibited the response to the beta-selective adrenergic agonist isoproterenol; thus, the existence of an adrenergic alpha 1-inhibitory receptor remained uncertain. Carbachol noncompetitively inhibited SLI secretion stimulated by gastrin, epinephrine, and dibutyryl cAMP. Atropine produced a parallel rightward shift of the carbachol dose-response curve (Ki = 0.4 nM). Pirenzepine also inhibited the effects of carbachol (Ki = 35 nM). Our studies suggest that SLI-containing cells in the canine fundic mucosa possess stimulatory beta-adrenergic receptors and inhibitory muscarinic receptors.
Enteric neurophysiology
Authors: Wood J. D.
Published: December 2017

Enteric neurophysiology is an emerging subspecialty of gastrointestinal biology. As such, it offers many investigative challenges and opportunities for advancement of understanding of gastrointestinal function. This review is organized to present the current status of enteric neurophysiology, to explain the controversies, and to explore the directions in which the subspecialty appears to be advancing. Current concepts of structural-functional relationships of the neuronal constituents of the enteric nervous system are presented in conjunction with electrophysiological and synaptic mechanisms. Relations between electrical and synaptic behavior of the neurons and information handling and integrative function within the local circuits are explored. Emergent properties of the system are considered in view of indications that the subsets of internuncial circuits that control each gastrointestinal effector are interconnected to ensure appropriate behavior that achieves coordination for optimal performance of the whole organ.
Differences in reactive hyperemia between the intestinal mucosa and muscularis
Authors: Shepherd A. P. , Riedel G. L.
Published: December 2017

In a previous study of regional intestinal blood flow by laser-Doppler velocimetry, we noted that the mucosa displayed reactive hyperemia following arterial occlusion but that the muscularis did not. Therefore, to determine whether this observation is generally valid, we compared responses of the mucosa and muscularis externa to arterial occlusion. We measured total blood flow to isolated loops of canine small bowel with an electromagnetic flow probe on the supply artery; blood flow either in the mucosa or in the muscularis was measured by laser-Doppler velocimetry. Mucosal and total blood flow consistently showed reactive hyperemia in response to a 60-s occlusion, but the muscularis did not. To determine whether metabolic rate influenced reactive hyperemia, we increased enteric oxygen uptake by placing 5% bile and transportable solutes in the lumen; these agents increased oxygen consumption by 36%. After a 60-s occlusion, the durations of both total and mucosal reactive hyperemia were significantly prolonged by increased metabolic rate. Similarly, the payback-to-debt ratios in both total and mucosal blood flows were significantly increased at elevated metabolic rate. These data support the conclusions that reactive hyperemia occurs more frequently and has a greater magnitude in the mucosa compared with the muscularis and both total and mucosal reactive hyperemia are strongly influenced by the preocclusive oxygen demand. These findings therefore constitute further evidence that metabolic factors contribute to reactive hyperemia in the intestinal circulation.
Epithelial response to intestinal anaphylaxis in rats: goblet cell secretion and enterocyte damage
Authors: Perdue M. H. , Forstner J. F. , Roomi N. W. , Gall D. G.
Published: December 2017

The effects of immunoglobulin E (IgE)-mediated reactions on the intestinal epithelium were examined during intestinal anaphylaxis in the rat. Rats sensitized by intraperitoneal injection of egg albumin (EA) plus alum developed high serum titers of IgE anti-EA antibodies after 14 days; sham-treated littermate controls had no anti-EA antibodies. Two isolated loops of jejunum were prepared in vivo in anesthetized rats. The loops were injected with EA in saline or saline alone, and intraluminal contents of each loop were examined after 4 h. Mucosal histamine decreased in sensitized rat intestine exposed to EA. Luminal mucin, measured by radioimmunoassay, was not increased by antigen challenge. In contrast, DNA, protein, and sucrase activities were elevated in contents from the isolated segments exposed to EA in sensitized rats. Histology revealed that periodic acid-Schiff-stained material was contained in goblet cells in sections prepared from these segments after antigen exposure. Cellular debris was present over the tips of the villi. These findings suggest that IgE-mediated reactions in the intestine cause epithelial damage and loss of material from cells other than goblet cells. The results indicate that release of goblet cell mucus is not a feature of intestinal anaphylaxis.
Erythromycin mimics exogenous motilin in gastrointestinal contractile activity in the dog
Authors: Itoh Z. , Nakaya M. , Suzuki T. , Arai H. , Wakabayashi K.
Published: December 2017

The gastrointestinal motor stimulating activity of erythromycin (EM) was studied in conscious dogs. It was found that a 20-min intravenous infusion of EM lactobionate at a dose of 50–100 micrograms (potency) X kg-1 X h-1 induced a group of strong contractions in the stomach and the duodenum, and the contractions migrated along the small intestine to the terminal ileum. The EM-induced contractions were quite similar to the naturally occurring interdigestive migrating contractions (IMC) in the gastrointestinal tract in frequency, contractile force, and duration of the contractions, migrating velocity, and accompanying peaks of plasma motilin concentration. The EM-induced contractions in the stomach were inhibited by feeding and intravenous infusion of pentagastrin (1.5 micrograms X kg-1 X h-1) but were not affected by secretin; these findings are identical to those found with the naturally occurring and motilin-induced contractions. Like motilin, EM stimulated motor activity only during the interdigestive state. We conclude that EM induces IMC associated with the release of endogenous motilin in the dog.
Effect of somatovisceral reflexes and selective dermatomal stimulation on postcibal antral pressure activity
Authors: Camilleri M. , Malagelada J. R. , Kao P. C. , Zinsmeister A. R.
Published: December 2017

Our objective was to elicit and characterize somatogastric reflexes in healthy humans. Sustained somatic stimulation by transcutaneous electrical nerve stimulation (TENS) was applied to the skin of human volunteers while simultaneously monitoring their upper gastrointestinal phasic pressure activity, extraintestinal vasomotor indices, and plasmalevels of putative humoral mediators of autonomic reflexes. Stimuli were applied either to the hand (C8–T1) or to the upper abdomen (T5–T10) to determine whether impulses at these two dermatomes produce different effects on fed antral phasic pressure activity. TENS resulted in significant reduction (P = 0.007) in antral motility index when applied to the hand and abdomen as compared with sham stimulation. This was associated with an increase in skin conductance and plasma beta-endorphin levels but no change in pulse, blood pressure, or circulating catecholamine levels. No qualitative changes in proximal intestinal pressure activity were detected. Sustained somatic stimuli resulted in reduced postprandial antral phasic pressure activity. The similarity of the responses to TENS applied to the hand and abdominal dermatomes suggests that the induced somatovisceral responses relay predominantly at the cerebral level.
Contribution of prostaglandins to dopamine actions in the pancreas of anesthetized dogs
Authors: Iwatsuki K. , Homma T. , Malik K. U.
Published: December 2017

We investigated the effect of dopamine and arachidonic acid on pancreatic blood flow and exocrine secretion in the isolated blood-perfused pancreas of pentobarbital sodium-anesthetized dogs without or with pretreatment with indomethacin or sodium meclofenamate in the absence and during infusion of prostaglandins I2 or E2 (PGI2 or PGE2). Intra-arterial administration of dopamine (50-500 ng/kg) produced an initial vasoconstriction followed by vasodilation and enhanced flow rate of pancreatic exocrine secretion. Arachidonic acid (0.5-5 micrograms/kg) produced vasodilation without altering the flow rate of pancreatic exocrine secretion. In animals pretreated with indomethacin or sodium meclofenamate (10 mg/kg iv), the magnitude and the duration of the biphasic vascular response but not the increase in flow rate of pancreatic exocrine secretion elicited by dopamine were reduced. Arachidonic acid-induced vasodilation was abolished by the cyclooxygenase inhibitors. During infusion of PGI2 or PGE2 (10 ng X kg-1 X min-1 ia), the inhibitory effect of indomethacin or sodium meclofenamate on the vasodilator phase of the response to dopamine was diminished. These data suggest that prostaglandins, presumably PGI2 and PGE2, contribute to the effect of dopamine to increase pancreatic blood flow but not to increase pancreatic exocrine secretion in anesthetized dogs.
Peptide YY inhibits meal-stimulated pancreatic and gastric secretion
Authors: Pappas T. N. , Debas H. T. , Goto Y. , Taylor I. L.
Published: December 2017

Peptide YY was recently isolated from porcine intestine and shown to exhibit marked structural homology with pancreatic polypeptide, a potent inhibitor of pancreatic exocrine secretion. We have examined the effects of infused peptide YY on gastric and pancreatic secretion in four mongrel dogs with gastric and pancreatic fistulas. A 15% liver extract meal was instilled intragastrically, and normal saline or one of three doses of peptide YY (200, 400, and 800 pmol X kg-1 X h-1) was infused into a peripheral vein. All three doses of peptide YY significantly inhibited meal-stimulated pancreatic fluid and bicarbonate secretion, with the lowest dose inhibiting secretion by 44.5 +/- 3.5 and 53.6 +/- 8.5%, respectively. Pancreatic protein secretion and gastric acid secretion were significantly inhibited by the two highest doses. The 200, 400, and 800 pmol X kg-1 X h-1 doses of peptide YY were associated with increments in peripheral blood of 201 +/- 24, 357 +/- 50, and 971 +/- 139 pM, respectively. These values compared with mean increments of 86.3 +/- 8.5 pM after a meat meal and 403 +/- 63 pM after intestinally perfused oleic acid. The present studies demonstrate that peptide YY inhibits gastric and pancreatic secretion and suggest that peptide YY may be the gastric and pancreatic inhibitor in ileocolonic mucosa that is released by perfusion of the intestine with oleic acid.
Neurotensin: a central neuromodulator of gastrointestinal motility in the dog
Authors: Bueno L. , Fioramonti J. , Fargeas M. J. , Primi M. P.
Published: December 2017

The effects of intracerebroventricular and intravenous injection of neurotensin on gastrointestinal and colonic motility were examined in fasted and fed conscious, intact, and vagotomized dogs. When administered intracerebroventricularly at 20 ng X kg-1 or higher doses in the fasted state, neurotensin reduced the duration of the periods of gastric motility for 3-4 h. During this time the jejunal migrating motor complex was replaced by isolated phases of regular activity occurring at a rhythm of 2-3/h, while colonic motility was unaffected. These effects were abolished after vagotomy and were not observed for 25 times higher doses when administered intravenously. Injected intracerebroventricularly at a dose of 100 ng X kg-1 30 min after a meal, neurotensin significantly reduced (P less than 0.01) the duration of the fed pattern (2.7 +/- 0.7 vs. 8.7 +/- 1.2 h for control); this effect was not observed when neurotensin was administered intracerebroventricularly 20 min before or 120 min after a meal or when injected intravenously. Systemic administration of neurotensin at a dose of 500 ng X kg-1 significantly increased (P less than 0.05) during 2 h the colonic motility indexes in both fasted and fed dogs before and after vagotomy. It is concluded that neurotensin can act i) centrally to control the pattern of antral and jejunal motility in the fasted and fed dogs, these effects being mediated by the vagus; and ii) peripherally to control the pattern of colonic motility, this response being unaffected by vagotomy.
Early effects of vitamin D metabolites on phosphate fluxes in isolated rat enterocytes
Authors: Karsenty G. , Lacour B. , Ulmann A. , Pierandrei E. , Drueke T.
Published: December 2017

The present studies were designed to explore the possibility that, in addition to its well-known steroidlike action, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], the active vitamin D3 metabolite, modulates inorganic phosphate (Pi) transport across the intestinal mucosa through more rapid membrane effects. Enterocytes were mechanically isolated from the duodenojejunum of vitamin D-replete rats. In this model enterocyte Pi uptake was a temperature-dependent as well as a Na+-dependent process. In vitro addition of 1,25(OH)2D3 (1 pM) led to a significant increase in Na+-dependent initial Pi uptake velocity (iVpi) within 20 min (P less than 0.001). No effect was seen for shorter incubation times (5 and 15 min). Incubation of the cells with cycloheximide did not inhibit the hormone-mediated increase of iVpi. 25-Hydroxyvitamin D3 significantly increased iVPi (P less than 0.05) at a concentration of 1 nM but not 1 pM. Vitamin D3 at a concentration of 1 microM had no effect on iVPi. Enterocyte Pi efflux rate constant was not modified by the presence of 1,25(OH)2D3(1pM). Thus, the early in vitro effect of 1,25(OH)2D3 on Pi uptake by isolated enterocytes suggests a nongenomic action of the hormone, possibly by modifying the lipid structure of the plasma membrane.
Transferrin and iron release from rat hepatocytes in culture
Authors: Baker E. , Page M. , Morgan E. H.
Published: December 2017

The regulation of transferrin and iron release from the liver was studied using adult rat hepatocytes in primary monolayer culture. The cells were prelabeled by incubation with rat transferrin doubly labeled with iodine-125 and iron-59. Approximately 50% of the 125I-transferrin but only 10% of the iron-59 taken up by the cells was released during reincubation for 24 h. Less than 10% of the refluxed transferrin was catabolized as indicated by the protein-free iodine-125 values. These results suggest that at least part of iron uptake by hepatocytes is mediated by the reversible binding of transferrin in a manner comparable with erythroid cells and placenta. However, several iron chelators mobilized hepatic iron, in contrast to erythroid cells. Apotransferrin and desferrioxamine released a maximum of about 20% iron-59 with little effect on transferrin binding. A greater proportion of the iron-59 was available for chelation after shorter uptake times (1-2 h) than longer times. Hence, there are at least three iron compartments in hepatocytes in culture: rapidly refluxing iron that may be transferrin bound, a fixed pool, and a chelatable pool that may represent iron in transit between plasma transferrin and ferritin.
Factors that influence absorption and secretion of calcium in the small intestine and colon
Authors: Favus M. J.
Published: December 2017

Intestinal epithelium absorbs calcium by an energy-dependent cellular process that is stimulated by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. Calcium entry across the brush border is driven by existing electrochemical gradients; exit across the basolateral membrane against these same gradients is driven by a calcium-activated ATPase, sodium-calcium exchange, or both. The specific cellular sites of 1,25(OH)2D3 action remain to be identified. Calcium transport is independent of phosphate and influenced by sodium. Sodium may alter calcium transport at the brush border through alterations of the transmembrane electrical gradient and at the basolateral membrane by exchange with intracellular calcium. The segmental distribution of calcium active transport is heterogeneous, with maximal flux rates in the proximal portions of small intestine and colon and net secretion in mid- and distal small intestine and mid-and distal colon. 1,25(OH)2D3 converts regions of net secretion in ileum and colon to net absorption. 1,25(OH)2D3-stimulated active phosphate transport is largely confined to areas of low-calcium transport, with maximal phosphate absorption in jejunum, the site of maximal calcium secretion. Calcium secretion, primarily in jejunum and ileum, is nonsaturable, may follow the paracellular pathway, and is stimulated by mucosal sodium and somatostatin.
Vasoactive intestinal polypeptide, cholecystokinin, glucagon, and bile-oleate-induced jejunal hyperemia
Authors: Gallavan R. H. , Chen M. H. , Joffe S. N. , Jacobson E. D.
Published: December 2017

The purpose of this study was to evaluate the roles of vasoactive intestinal polypeptide (VIP), cholecystokinin (CCK), and glucagon in the local regulation of the lipid-induced intestinal hyperemia. Total blood flow and the arteriovenous hormone concentration gradient were measured in isolated jejunal loops of anesthetized dogs with either saline, bile (10% in normal saline), oleic acid (40 mM in normal saline), or oleic acid and bile in the lumen. The bile-oleic acid mixture increased both blood flow (+21 +/- 7%) and VIP release (+118 +/- 7%), while CCK release was considerably less. There was a transient rise in glucagonlike immunoreactivity but no change in pancreatic glucagon release. Neither bile nor oleic acid alone altered either local blood flow or hormone release. Infusion of VIP into the arterial circulation of the jejunum significantly reduced vascular resistance (-11 +/- 4%) but at a dose (150 ng . min-1 X 100 g-1) 10 times that released in response to the bile-oleic acid mixture. This study indicates that oleic acid increases both blood flow and intestinal hormone production only when present in the lumen in micellar form and suggests that VIP could play a role in the jejunal vascular response to fat.
Sleeve device functions as a Starling resistor to record sphincter pressure
Authors: Linehan J. H. , Dent J. , Dodds W. J. , Hogan W. J.
Published: December 2017

In 1976 Dent (Gastroenterology 71: 263–267) introduced a sleeve-catheter device for obtaining continuous recording of lower esophageal sphincter pressure. The infused sleeve accommodates for axial sphincter movement by providing a large surface of collapsible membrane that is capable of sensing maximal sphincter pressure at any point along the sleeve. Although sleeve performance was tested previously, the precise physical principal of its function has not been delineated. This study tests the hypothesis that the sleeve device functions as a Starling resistor. The term “Starling resistor” is an eponym that designates the physics of fluid flow through collapsible tubes. When pressure at any point along an infused collapsible conduit is greater than the intraluminal pressure at the distal end of the conduit, partial collapse occurs at some axial location along the conduit where the transmural pressure equals zero. The location of zero transmural pressure is termed the “equal pressure point” (EPP). The partial collapse at the EPP causes a local change in luminal resistance that is directly related to the magnitude of the external pressure at the EPP and accompanied by a corresponding change in the pressure upstream from the EPP. A correlate to the performance of Starling resistors is that the pressure upstream to the EPP is not affected by the downstream pressure, so long as the downstream pressure is less than the external pressure. To test our hypothesis, we evaluated sleeve performance in vitro using a two-chambered model that allowed application of static or oscillatory pressures at one or two sites along the sleeve.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of pancreatic polypeptide, caerulein, and bombesin on satiety in obese mice
Authors: Taylor I. L. , Garcia R.
Published: December 2017

Congenitally obese mice are hyperphagic, suggesting that their obesity is secondary to defects in normal satiety mechanisms. The present study compares the effects of caerulein, bombesin, and pancreatic polypeptide (three equimolar doses each of 3, 9, and 27 nmol/kg) on food intake in 10 pairs of lean and obese mice. After the intraperitoneal injection of saline, obese mice eat 240% more of a liquid meal (Magnacal) than their lean littermates (P less than 0.01). All three doses of caerulein significantly inhibited food intake in both obese and lean mice. Although the highest dose of bombesin significantly decreased food intake in both obese and lean mice, the lowest dose was only effective in obese mice. In contrast, none of these doses of pancreatic polypeptide had a significant effect on food intake in either lean or obese mice. A dose of bovine pancreatic polypeptide of 200 nmol/kg was required to significantly reduce food intake in lean and obese mice. This study demonstrates that obese mice respond to satiety signals and may even be more sensitive than their lean littermates to some messengers. In addition, the previously described reversal of this obesity syndrome by pancreatic polypeptide in doses of approximately 2.5 and 25 nmol X kg-1 X day-1 is unlikely to be due to effects of this peptide on food intake.
Increased ethanol consumption and blood ethanol levels in rats with portacaval shunts
Authors: Martin J. R. , Porchet H. , Buhler R. , Bircher J.
Published: December 2017

In a series of experiments, it was demonstrated that male rats with end-to-side portacaval shunts (PCS) consumed more ethanol and exhibited higher blood ethanol levels than sham-operated control animals in chronic tests with 2% ethanol and water ad libitum. Ethanol intake in the 6 h prior to blood sampling was 2-5 times and blood ethanol 10-50 times higher in PCS than control rats. These effects were not due to the feminization of male rats occurring after a PCS, since female PCS rats exhibited comparable increases of ethanol intake and blood ethanol. In both sexes ethanol elimination rate and alcohol dehydrogenase activity per total liver were lower after PCS than in control rats, explaining the disproportionate increase in blood ethanol relative to ethanol intake. Interestingly, ethanol intake was not abnormal in PCS rats fed a low-protein, low-tryptophan diet (corn) alone or as a supplement to the usual chow diet. Such dietary modulation of ethanol preference in this animal model of chronic liver dysfunction merits further attention.
Failure of 16,16-dimethyl PGE2 to prevent inhibitory effect of ethanol on sodium transport in canine gastric mucosa
Authors: Miller T. A. , Henagan J. M. , Kuo Y. J. , Shanbour L. L.
Published: December 2017

By use of an in vitro canine gastric mucosal preparation, we evaluated the effects of ethanol (2, 4, 6, and 8%, vol/vol) and indomethacin (2.2 X 10(-4)M), with and without 16,16-dimethyl PGE2 pretreatment, on net sodium transport (JNanet) (mucosal to serosal) across gastric epithelium. Although administration of 2 or 4% ethanol to the mucosal bathing solution had no appreciable inhibitory effects on sodium transport, 6 and 8% ethanol and indomethacin significantly inhibited JNanet when compared with untreated control mucosa. This effect was accompanied by inhibition of transmucosal potential difference (PD) and short-circuit current (Isc). In other mucosae exposed to dimethyl PGE2 (8 X 10(-6) M) in the serosal bathing solution, significant increases in JNanet, PD, and Isc were noted when compared with control mucosa. Addition of 6 or 8% ethanol to the mucosal solution of dimethyl PGE2-pretreated tissue resulted in significant decreases in PD, Isc, and JNanet below control values that were not significantly different from mucosa exposed to 6 and 8% ethanol without PG pretreatment. When indomethacin was added to the mucosal solution following dimethyl PGE2 pretreatment, only slight decreases in PD and Isc below control levels were observed, and the inhibitory effects on JNanet induced by indomethacin without such treatment were abolished. These findings suggest that stimulation of JNanet by prostaglandin may play a role in its ability to prevent indomethacin damage to gastric epithelium but does not appear to be of importance in mediating protection against ethanol damage.
Studies of carnitine metabolism in relation to intestinal absorption
Authors: Gudjonsson H. , Li B. U. , Shug A. L. , Olsen W. A.
Published: December 2017

We studied the postabsorptive fate of L-[3H]carnitine after intraluminal injection into the proximal intestine of anesthetized rats. Carnitine absorption was characterized by slow appearance in the circulation with blood levels still rising 2 h after administration. Absorption via the portal vein was followed by hepatic extraction and appearance in bile with reabsorption of a fraction, thus establishing an enterohepatic circulation. About half of the [3H]carnitine in blood obtained 4 h after administration was free, with the rest largely acetylcarnitine. In contrast the increase in blood carnitine content after intraluminal administration of unlabeled carnitine was almost exclusively limited to the esterified fraction. We hypothesize that release of esterified endogenous or stored carnitine from some other site accounted for the increase in esterified carnitine. The liver may be that site: although about 50% of hepatic [3H]carnitine was in ester form after administration of labeled carnitine, the increase after unlabeled carnitine was primarily in the free fraction, suggesting that a large amount of esterified carnitine had been released. Thus the liver appears to be an important storage and excretory site for exogenous as well as endogenous carnitine, which may be released with an appropriate signal from the intestine.
Intestinal uptake and release of cobalamin complexed with rat intrinsic factor
Authors: Seetharam B. , Presti M. , Frank B. , Tiruppathi C. , Alpers D. H.
Published: December 2017

The mechanism of uptake of intrinsic factor (IF) and cobalamin (Cbl) by enterocytes and their subsequent fate have been uncertain. To examine this problem double-labeled IF X Cbl was added to small intestinal organ cultures. When 125I-IF X [57Co]Cbl was added to rabbit ileal explants, binding and internalization increased linearly for 24 h. After an 18-h chase with nonlabeled IF X Cbl, no 125I-IF returned to the cell surface. An amount of 35-45% of the internalized Cbl was found free, not bound to IF or any other protein. About 60% of both internalized ligands was bound to membranes but by a non-Ca2+-dependent bond, suggesting binding to a protein other than the brush-border receptor. Cobalamin was released from IF at pH 5.0 to the same degree (30%) as free Cbl was found inside the cell (35-45%). Neither pancreatic proteases nor ileal homogenates effected release of Cbl from IF. When cathepsins were added, the Cbl released was no greater than could be attributed to pH 5.0 alone. Chloroquine added to tissue explants did not alter the percentage of free intracellular Cbl. From these results we suggest that IF X Cbl is internalized and detached from the receptor within the enterocyte. The mechanism of release is not known but seems to require an acid pH (5.0). The Cbl is released in the mucosa, perhaps when the IF X Cbl complex enters a nonlysosomal cellular compartment with an acidic environment. There is no substantial recycling of IF to the brush-border membrane.
Dissociated effects of somatostatin on gastric acid secretion and mucosal blood flow
Authors: Leung F. W. , Guth P. H.
Published: December 2017

Somatostatin has been reported to control upper gastrointestinal hemorrhage, prevent restraint stress-induced gastric ulcerations, and inhibit gastric acid secretion. In this study we examined the effect of somatostatin on basal and pentagastrin-stimulated gastric acid output and mucosal blood flow. Antral and corpus mucosal blood flows were measured by hydrogen gas clearance in fasted, anesthetized rats. Acid output was determined by a continuous gastric perfusion technique. In the basal study somatostatin in doses of 8, 16, and 32 micrograms . kg-1 . h-1 was infused intravenously in separate groups of animals. In the pentagastrin stimulation study somatostatin (16 micrograms . kg-1 . h-1) was infused after gastric acid output was stimulated to plateau by intravenous pentagastrin (19.8 micrograms . kg-1 . h-1). The results showed that somatostatin had no effect on basal corpus or antral mucosal blood flow. During pentagastrin stimulation somatostatin decreased acid secretion but increased corpus mucosal blood flow. We speculate that this increase in blood flow may not be a direct effect as basal corpus or antral mucosal blood flow was unaffected by somatostatin.
Role of prostaglandins in control of intestinal motility
Authors: Thor P. , Konturek J. W. , Konturek S. J. , Anderson J. H.
Published: December 2017

Intestinal myoelectric activity was measured in four conscious dogs with implanted monopolar electrodes after administration of prostaglandins (PG) and indomethacin (Indo), a potent inhibitor of PG biosynthesis. PGE2 and PGI2 given intravenously caused a dose-dependent decrease in the frequency of the migrating myoelectric complex (MMC) in fasted dogs and in postprandial spike activity in fed animals. In contrast, PGF2 alpha interrupted the MMC and caused a fedlike pattern in fasted dogs and did not affect the postprandial spike activity. Similar effects were observed after intra-arterial infusion of PGs. PGE2 and PGI2 infused into the superior mesenteric artery caused a dose-dependent inhibition of the fasted and postprandial pattern of myoelectric activity of the small bowel, whereas PGF2 alpha blocked the MMC and increased spike activity. Indo injected in a single intravenous dose caused a significant reduction in the MMC interval, and Indo infused intravenously in a constant dose induced fedlike motility pattern in fasted dogs but had little effect on the postprandial activity in these animals. This study demonstrates that exogenous PGs of E and I series administered intravenously or intra-arterially inhibit intestinal motility, whereas PGF2 alpha has opposite effects. The finding that Indo increases intestinal motility indicates that endogenous PGs are important in the physiological control of intestinal motility.
Tricyclic antidepressants and acid secretory response of rabbit gastric cells
Authors: Batzri S.
Published: December 2017

Tricyclic antidepressants have been tested for their effect on the H2-receptor-mediated changes in cAMP, O2 consumption, and acid secretion in mucosal cells isolated from rabbit stomach. Amitriptyline (AMT) inhibited the action of histamine on both cAMP generation and O2 consumption in an apparent competitive fashion without altering these parameters in unstimulated cells. The onset of this inhibition was rapid and the time at which the increases in these functions had reached steady state was not changed. The Schild regression line for AMT was close to unity, and its Ki values for cAMP production or O2 consumption were 0.75 microM AMT. Imipramine and nortriptyline also caused a rightward shift in the dose-response curve of histamine-induced cAMP generation. The inhibitory action of AMT was specific to histamine in that AMT neither altered the effect of isobutylmethylxanthine on cAMP and respiration nor inhibited the increase in respiration caused by carbachol. However, at relatively high concentrations (250-500 microM), AMT inhibited the increase in cAMP caused by 5 and 100 microM prostaglandin E1 and inhibited the increase in respiration caused by both dibutyryl cAMP (DBcAMP) and by the combination of DBcAMP plus carbachol. Antidepressant drugs were also very potent inhibitors of acid formation as measured by [14C]aminopyrine accumulation (Ki, 1 microM). They inhibited acid formation in control cells, in cells stimulated by histamine, carbachol, and DBcAMP, and also the potentiated response to carbachol plus histamine or DBcAMP. The onset of this inhibition was also rapid, and adding 5 microM AMT to the cell suspension either together with histamine or after stimulation by histamine caused a rapid decline in aminopyrine accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Regional specificity of iron uptake by small intestinal brush-border membranes from normal and iron-deficient mice
Authors: Muir A. , Hopfer U.
Published: December 2017

Fe(II)-ascorbate uptake by purified small intestinal brush-border membrane vesicles prepared from proximal and distal segments was studied in normal and iron-deficient mice. Iron was maintained in a reduced, soluble form by a 20-fold excess of ascorbate at a physiological pH of 7.2-7.4. In normal mice, iron uptake by proximal membrane vesicles was three- to fourfold greater (approximately 1,700 pmol/mg prot) than from distal segments (approximately 500 pmol/mg prot). In iron-deficient mice, uptake of Fe(II) was also greater in proximal membranes (approximately 3,200 pmol/mg prot) than uptake from distal segments (approximately 350 pmol/mg prot), and the regional difference was almost 10-fold, without any change in distal segmental iron uptake. These results are consistent with the pattern of intestinal iron absorption in iron-replete and iron-deficient animals and indicate that regulatory changes in proximal intestinal brush-border membranes may account for the increased iron absorption known to occur in iron deficiency.
Effects of varying hematocrit on intestinal oxygen uptake in neonatal lambs
Authors: Holzman I. R. , Tabata B. , Edelstone D. I.
Published: December 2017

We chronically catheterized 15 newborn lambs (9.5 +/- 2.8 days) and measured intestinal blood flow (Qi) by the radionuclide microsphere technique at hematocrit levels ranging from 10 to 55%. Seven animals were made progressively anemic and eight polycythemic by means of exchange transfusions. Using the Fick principle, we calculated intestinal oxygen delivery (Di o2), oxygen consumption (Vi o2), and oxygen extraction. Initial base-line values were Qi = 195.5 ml . min-1 . 100 g intestine-1, Di o2 = 22.1 ml . min-1 . 100 g-1, Vi o2 = 4.8 ml . min-1 . 100 g-1, and O2 extraction = 22.5%. As the hematocrit was lowered, Di o2 decreased and O2 extraction increased and vice versa when the hematocrit was raised. Vi o2 remained constant, but Qi did not correlate with changes in hematocrit. However, intestinal blood flow, as a percent distribution of total blood flow, decreased with lower hematocrit levels. At no time was there any evidence of anaerobic metabolism as measured by excess lactate production. Our data indicate that the intestines of neonatal lambs are capable of maintaining their metabolic needs over a wide range of oxygen availability induced by a changing hematocrit. The primary mechanism is through alteration of oxygen extraction. Within the range of our experiments, no critically low oxygen availability was attained at which anaerobic metabolism became significant.
Regulation of capillary exchange capacity in the dog stomach
Authors: Perry M. A. , Granger D. N.
Published: December 2017

The capillary exchange capacity of the isolated, perfused dog stomach was investigated during vasoconstriction (norepinephrine) and vasodilation (isoproterenol) and compared with values obtained when blood flow to the stomach was decreased or increased mechanically. The capillary filtration coefficient (Kf,c) was used as an index of capillary exchange capacity. Under resting conditions, Kf,c in the isolated stomach was 0.20 +/- 0.02 ml . min-1 . mmHg-1 . 100 g-1. Vasoconstriction and mechanical reduction in blood flow caused Kf,c to fall to 68 and 58% of control, while vasodilation and mechanical increase in blood flow caused Kf,c to rise to 176 and 231% of control, respectively. Pentagastrin produced an increase in gastric oxygen consumption and a 50% increase in Kf,c. In all instances, capillary exchange capacity appeared to be correlated with gastric blood flow. The data suggest there is little local control of precapillary sphincter tone in the stomach and that capillary exchange capacity may be governed by local pressure within the microvasculature.
Inhibition of neurally mediated gastrin secretion by bombesin antiserum
Authors: Schubert M. L. , Saffouri B. , Walsh J. H. , Makhlouf G. M.
Published: December 2017

In vitro studies on the vascularly perfused rat stomach have shown that gastrin secretion is regulated by intramural cholinergic and noncholinergic neurons. We have postulated that bombesin (gastrin-releasing peptide), a known gastrin stimulant present in antral mucosal nerve fibers, is the most likely candidate for noncholinergic transmitter. Bombesin antiserum (final dilution, 1:150) but not control serum added to the vascular perfusate inhibited the gastrin response to 1,1-dimethyl-4-phenylpiperazinium by 59 +/- 17% (P less than 0.01) and to electrical field stimulation by 60 +/- 16% (P less than 0.01), and its effect was additive to that of 10(-7) M atropine (75-94%), thus accounting for the greater part of neurally induced gastrin secretion. The effects of atropine and bombesin antiserum on somatostatin secretion were consistent also with blockade of cholinergic and noncholinergic neurons, respectively. The results indicate that bombesin and acetylcholine are the main intramural neural regulators of gastrin and somatostatin secretion. Acetylcholine acts predominantly to decrease the paracrine secretion of somatostatin, thereby eliminating the continuous restraint of somatostatin on gastrin secretion and enabling bombesin to exert its potent stimulatory effect on gastrin secretion.
Effects of sulfodeoxycholate on rat and rabbit small intestine
Authors: Ammon H. V. , Tapper E. J. , Komorowski R. A. , Charaf U. K. , Loeffler R. F. , Lewand D. , Walter L. G.
Published: December 2017

To determine how sulfation alters the biological properties of dihydroxy bile acids, we compared the effects of 3-sulfodeoxycholate (SDC) and deoxycholate (DC) in the rat and rabbit intestine. While 5 mM DC induced water and electrolyte secretion and inhibited glucose absorption in the rat, SDC enhanced jejunal and ileal water and solute absorption. SDC had no effect in the rabbit ileum. In the rat jejunum DC caused mucosal injury and enhanced mucosal permeability while SDC had no effect. In vitro in the rabbit ileum, 10 mM SDC enhanced net sodium flux and decreased net residual flux, while 0.5 mM DC reduced net sodium flux and induced Cl- secretion. Both bile acids increased short-circuit current and potential difference and decreased tissue conductance. During reversed-phase, high-performance liquid chromatography SDC was more polar than DC. Sulfation reduced the ability of DC to destroy large unilamellar liposomes by a factor of 10. Thus, sulfation abolishes the effects of DC on the intestine by enhancing the polarity of this molecule. The enhancement of intestinal solute and water absorption by SDC requires further study.
Carbamoyl-phosphate synthetase I activity and ureagenesis in regenerating liver of the normal rat
Authors: Goodman M. W. , Zieve L.
Published: December 2017

Urea excretion per gram of liver was increased 219% 2-5 h post-partial hepatectomy (Hx) and 45% 24-27 h post-Hx. Mitochondrial carbamoyl-phosphate synthetase was also increased 5 h post-Hx but was not increased at 27 h. An NH4+ load did not increase urea excretion per gram liver or the enzyme activity noticeably in the 2- to 5-h period but did increase them 24-27 h post-Hx. These results suggest that the enzyme activity and urea formation per unit weight of liver were nearly maximal early during regeneration. Orotic acid excretion per gram of liver in rats that received NH4+ was increased more than 30-fold 2-5 h post-Hx and was similar in this respect to nonhepatectomized rats. Ornithine prevented the increase in both normal and hepatectomized rats, suggesting that ornithine was rate limiting for the ornithine carbamoyltransferase (OCT) reaction. The orotic acid excretion response to NH4+ was much less 24-27 h post-Hx, indicating that ornithine availability for the OCT reaction may be increased at this time.