bluuebunny/crossref_metadata_2025 huggingface dataset:
Internal biliary diversion improves glucose tolerance in the rat
Authors: Manfredini G. , Ermini M. , Scopsi L. , Bonaguidi F. , Ferrannini E.
Published: December 2017

The gastrointestinal tract is known to generate hormonal and neural signals that can affect the endocrine function of the pancreas ("enteroinsular axis"). The physiological circumstances under which this connection is operative are still a matter of debate. We investigated the influence of bile flow on glucose homeostasis in an experimental model of internal biliary diversion. After laparotomy in 2-mo-old rats, bile flow was diverted from the duodenum into the second jejunal loop with the use of a plastic minicannula. Rats in which the cannula was implanted but not connected with the common bile duct (sham operation) and rats receiving no treatment were used as control groups. After surgery, the rats with the biliary bypass weighed 10% less than the controls for 3 wk; afterwards and until 9 mo later, operated and nonoperated animals had similar growth curves. After the operation, fasting plasma glucose concentrations fell significantly in the treated rats compared with both sham-operated and control rats; likewise, the glycemic response to orally administered glucose was lower in the treated group 1 wk after surgery. In contrast, no significant difference was found in either the fasting or the glucose-induced plasma insulin levels. Nine months after surgery, the same three groups of animals received an oral glucose tolerance test, an intravenous glucose tolerance test, and a fasting-refeeding test (24 h of fast followed by standard, mixed feeding for another 24 h). On all three tests, bile-diverted rats showed lower plasma glucose responses than either sham-operated or control rats in the face of essentially similar plasma insulin responses.(ABSTRACT TRUNCATED AT 250 WORDS)
Ontogenesis of intestinal transport of 5-methyltetrahydrofolate in the rat
Authors: Said H. M. , Ghishan F. K. , Murrell J. E.
Published: December 2017

Developmental aspects of the intestinal transport of 5-methyltetrahydrofolate (5-CH3H4-PteGlu) were studied in suckling (14-day-old), weanling (22-day-old), and adult (90-day-old) rats by use of the intestinal everted-sac technique. Mucosal-to-serosal transport of 0.5 microM 5-CH3H4PteGlu was linear with time for 40-min incubation and occurred at a rate of 0.035, 0.032, and 0.010 nmol X g initial tissue wet wt-1 X min-1 for suckling, weanling, and adult rats, respectively. The transport of 5-CH3H4PteGlu in all age groups was pH dependent (maximal at pH 6) and was higher in the jejunum than in the ileum. In all age groups the transport of 5-CH3H4PteGlu occurred by an active carrier-mediated system. The system was saturable; energy, temperature, and Na dependent; inhibited by structural analogues; and capable of accumulating the substrate against a concentration gradient. Kinetic parameters of the transport process, however, showed some difference. A progressive decrease in Vmax was observed from suckling to weanling to adult rats (5.1, 3.7, and 0.8 nmol X g initial tissue wet wt-1 X 30 min-1, respectively), while apparent Kt was similar (2.2, 1.73, and 1.79 microM, respectively). This study demonstrates that the transport system of 5-CH3H4PteGlu in the rat is fully developed at the suckling age. The results also suggest that the activity and/or the number, but not the affinity, of the transport carriers decrease with maturation.
Relation between antral motility and gastric emptying of solids and liquids in humans
Authors: Camilleri M. , Malagelada J. R. , Brown M. L. , Becker G. , Zinsmeister A. R.
Published: December 2017

Our aim was to test the hypothesis that there is a relation between antral phasic pressure activity and the emptying of solids and liquids from the intact human stomach after a mixed meal. This hypothesis was evaluated in 14 healthy individuals in whom we performed simultaneous antral manometry and radioscintigraphy after ingestion of a meal labeled with [99mTc]sulfur colloid in cooked egg (solid component) and [111In]DTPA (liquid component). Analysis of the data included an in-depth evaluation of different models for expressing both gastric emptying rates and antral pressure activity. We found that gastric emptying was adequately represented by a two-phase model consisting of lag and emptying periods and by a power exponential model for the liquid phase. Distal antral motility was accurately represented by the slope of the cumulative antral motility index. During the lag period for solids, the antral motility was inversely related to the duration of the lag. During the solid-emptying period, there was a positive correlation between emptying of solids and antral motility. No significant relation was found between antral motility and overall emptying of the liquid phase of the meal. However, a relationship was found when antral motility was related to liquid emptying after an initial lag period for solids. These human data are consistent with a role of antral pressure activity in trituration of solid food and a role of the antrum in the subsequent propulsion of solids and liquids from the stomach.
Prostaglandin-induced pepsinogen secretion from dispersed gastric glands from guinea pig stomach
Authors: Berger S. , Raufman J. P.
Published: December 2017

We examined the actions of several prostaglandins (PG) on pepsinogen secretion from dispersed gastric glands prepared from guinea pig stomach. Pepsinogen secretion was stimulated by PGA1, PGA2, PGB2, PGE1, and PGE2. PGE1 and PGE2 were 10 times more potent than PGA1 and PGA2. Reducing the incubation temperature from 37 degrees to 4 degrees C or adding carbonyl cyanide m-chlorophenylhydrazone reduced PG-stimulated pepsinogen secretion. PGE2-induced pepsinogen secretion was not altered by atropine or dibutyryl cGMP. Potentiation of pepsinogen secretion occurred with PGE2 plus carbachol or the calcium ionophore A23187 but not with PGE2 plus secretin or 8-bromo-cAMP. Isobutylmethylxanthine increased the potency and the efficacy of the action of PGE2 on pepsinogen secretion. These results indicate that PGE1, PGA2, PGB2, PGE1, and PGE2 can modulate pepsinogen secretion from dispersed gastric glands from guinea pig stomach. Moreover, potentiation of pepsinogen secretion occurs when PGE2 is combined with secretagogues whose actions appear to be mediated by changes in cellular calcium (carbachol and A23187) but not with secretagogues whose actions appear to be mediated by changes in cellular cAMP (secretin and 8-bromo-cAMP). These data suggest that PG-induced pepsinogen secretion may be mediated by changes in cellular cAMP.
pH gradient-stimulated sulfate transport by rabbit ileal brush-border membrane vesicles: evidence for SO4-OH exchange
Authors: Schron C. M. , Knickelbein R. G. , Aronson P. S. , Della Puca J. , Dobbins J. W.
Published: December 2017

In the presence of a pH gradient (7.7 inside, 5.5 outside), the initial velocity of SO4 uptake by rabbit ileal brush-border membrane (BBM) vesicles was markedly stimulated compared with uptake in the absence of a pH gradient. Under pH gradient conditions, SO4 was transiently accumulated at a concentration 13-fold higher than at equilibrium ("overshoot"). Superimposition of a HCO3 gradient did not further stimulate the initial velocity of SO4 uptake compared with a pH gradient alone. Evidence that this pH gradient-stimulated SO4 uptake represented SO4-OH exchange included lack of sensitivity of SO4 transport to alterations of the membrane potential; 85-95% inhibition of SO4 uptake by the anion exchange inhibitors DIDS and SITS; and saturation kinetics (Km for SO4 = 0.475 +/- 0.054 mM; Vmax = 4.1 +/- 0.1 nmol SO4 X mg prot-1 X min-1). Sulfate did not inhibit pH gradient-stimulated 36Cl uptake, indicating that SO4-OH and Cl-HCO3(OH) are different exchangers. When BBM vesicles were compared with basolateral membrane (BLM) vesicles, pH gradient-stimulated SO4 uptake was found predominantly in the BBM preparation. Brush-border SO4-OH exchange was further localized by demonstrating Na-stimulated SO4 efflux from vesicles loaded under pH gradient conditions, suggesting that Na-SO4 cotransport and SO4-OH exchange are on the same BBM vesicles. In conclusion, a SO4-OH exchanger (or H-SO4 cotransporter) exists on the brush border of rabbit ileum which is distinct from the brush-border Cl-HCO3(OH) exchanger.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of epidermal growth factor on ontogeny of the gastrointestinal tract
Authors: O'Loughlin E. V. , Chung M. , Hollenberg M. , Hayden J. , Zahavi I. , Gall D. G.
Published: December 2017

The effect of epidermal growth factor (EGF) on the ontogeny of the gastrointestinal tract was examined in New Zealand White rabbits. EGF, 40 micrograms X kg-1 X day-1, was administered to suckling animals from 3-18 days of age either intraperitoneally or orogastrically. Controls received saline. Animals were killed at 17-18 days of age. Body weight and wet weight of stomach, pancreas, and 10-cm segments of proximal, mid, and distal small intestine were measured. The total pancreas was homogenized for determination of protein, DNA, and amylase, and the intestinal mucosa was scraped, weighed, and homogenized for estimation of protein, DNA, sucrase, and lactase. While body weights were similar wet weight of stomach and pancreas were increased by intraperitoneal and orogastric EGF. Small intestinal wet weights were increased in all segments by intraperitoneal but not orogastric EGF, and both routes significantly increased mucosal DNA in the distal segment. EGF administered orogastrically induced precocious maturation of intestinal brush-border disaccharidase activities but had no effect on pancreatic amylase, whereas EGF administered intraperitoneally induced precocious maturation of pancreatic amylase but had no effect on brush-border disaccharidase activities. These findings suggest that both systemic and oral EGF play a role in regulating growth and postnatal maturation of the gastrointestinal tract.
Role of extracellular Ca2+ in hepatic bile formation and taurocholate transport
Authors: Anwer M. S. , Clayton L. M.
Published: December 2017

The role of extracellular Ca2+ in hepatic bile formation, biliary membrane permeability, and taurocholate (TC) transport was studied in isolated perfused rat livers and in isolated rat hepatocytes to determine the functional importance of paracellular permeability in biliary bile acid excretion. Each liver was perfused for 1 h with perfusate containing 1.3 mM Ca2+ (control period) followed by another hour with 1.3, 0.5, 0.1, 0.05, 0.03, or 0.01 mM Ca2+ (experimental period). Basal bile flow and biliary excretion of added TC declined significantly only at and below 0.05 mM perfusate Ca2+ and was associated with an increase in bile-to-perfusate concentration ratio of [3H]inulin (B/P inulin ratio). A twofold increase in the diffusional permeability coefficient at 0.05 mM and a sixfold increase at 0.03 and 0.01 mM perfusate Ca2+ could explain the increased in B/P inulin ratios. Time-dependent increases in cell-to-medium concentration ratios of inulin were less in the absence than in the presence of Ca2+. Hepatic uptake rates of TC determined in isolated hepatocytes and from perfusate disappearance of added TC and efflux rates of TC from preloaded hepatocytes were not significantly affected by Ca2+ removal. It is possible that the observed decline in biliary TC excretion at low perfusate Ca2+ is due to regurgitation of secreted TC back into the perfusate followed by reuptake. This was supported by an accumulation of perfusate radioactivity when TC uptake inhibitors (furosemide and bumetanide) were added to the perfusate (0.03 mM Ca2+) 60 min after the addition of [14C]TC.(ABSTRACT TRUNCATED AT 250 WORDS)
Blood pressure changes after gastric mechanical and electrical stimulation in rats
Authors: Pozo F. , Fueyo A. , Esteban M. M. , Rojo-Ortega J. M. , Marin B.
Published: December 2017

The effect of different stimuli applied in several parts of the digestive tract on blood pressure was studied in unconscious Wistar rats. Gastric distension and electrical and pinching stimuli produced a significant increase in both systolic and diastolic arterial blood pressure. When different gastric zones were stimulated by either electrical or pinching stimuli, the highest pressor response was found in the antropyloric zone. The stimuli applied to the small intestine, outside the duodenum, did not modify the blood pressure. The pinching of the abdominal peritoneum caused a pronounced (P less than 0.001) blood pressure decrease. These data suggest that the pressor response to gastric distension could be mediated by gastric mechanoreceptors. The pressor response observed after stimulation of the gastric antropyloric zone suggests that this area has a greater number of mechanoreceptors.
Regional distribution and release of peptide YY with fatty acids of different chain length
Authors: Aponte G. W. , Fink A. S. , Meyer J. H. , Tatemoto K. , Taylor I. L.
Published: December 2017

The present study examines peptide YY responses to regional intestinal perfusion of fatty acids of different chain length--dodecanoate and oleate. Six dogs with chronic gastric, duodenal, and jejunal fistulas were studied. Proximal perfusates were administered into the duodenum and diverted through an intestinal fistula placed 45 cm beyond the duodenal cannula. Distal perfusates were administered into the caudal stoma of this intestinal stoma. Peptide YY responses to proximal, distal, and whole-gut perfusion were compared. Proximal perfusion with oleate or dodecanoate failed to release peptide YY. In contrast, distal and whole-gut perfusion with either fatty acid produced significant increases that were of similar magnitude. Immunocytochemical studies demonstrated that peptide YY cells predominated in the canine ileocolonic mucosa and decreased progressively in an orad direction. We conclude that peptide YY release is not dependent on fatty acid chain length and that the duodenum does not play a dominant role in peptide YY release. As such, peptide YY release differs from that of its cousin pancreatic polypeptide and may result at least in part from direct stimulation of the peptide YY cell in the ileocolonic mucosa.
Gastrin receptors in normal and malignant gastrointestinal mucosa: age-associated changes
Authors: Singh P. , Rae-Venter B. , Townsend C. M. , Khalil T. , Thompson J. C.
Published: December 2017

Synthetic human gastrin 17-I (MG) and an analogue, [Leu15]gastrin-17-I (LG), were radiolabeled with Na125I by Iodo-Gen, EnzymoBead, and chloramine-T methods, and the characteristics of the radiolabeled peptides were determined. When 125I-MG was iodinated by chloramine-T, its biological activity and its binding activity were almost abolished, whereas the biological activity of 125I-LG, iodinated by either of the methods, and of 125I-MG, iodinated by Iodo-Gen and EnzymoBeads, was not significantly affected. The kinetics, affinity, and specificity of binding of 125I-MG, iodinated by Iodo-Gen, to crude and purified membranes from rat fundic mucosa were examined and found to be similar to that for 125I-LG. Age-associated changes in the number and affinity of gastrin receptors (GR) on the crude membranes of gastrointestinal mucosa of rats was also examined. Significantly fewer GR were observed on the crude membranes of fundic mucosa of aged (24 mo old) compared with young (3- and 6-mo-old) rats. In addition, specific gastrin-binding sites (4.7 +/- 0.9 fmol/mg prot) with low affinity (Kd = 3.7 +/- 1.2 nM) were observed in the antrum of aged rats, the significance of which is not understood. There were, however, no differences in the number and characteristics of GR in other regions of the intestine of old and young rats. The presence of GR was additionally assessed in cell lines of gastrointestinal cancers from humans, mice, and hamsters.(ABSTRACT TRUNCATED AT 250 WORDS)
Inhibition of intestinal citrulline synthesis causes severe growth retardation in rats
Authors: Hoogenraad N. , Totino N. , Elmer H. , Wraight C. , Alewood P. , Johns R. B.
Published: December 2017

delta-N-(phosphonacetyl)-L-ornithine (PALO) is a powerful and specific inhibitor of ornithine transcarbamylase (1), but it does not readily enter intact cells and therefore does not inhibit citrulline synthesis in intact liver or intestine. We have used the glycylglycine derivative of PALO (Gly-Gly-PALO) to evaluate the importance of intestinal citrulline synthesis in supplying arginine for growth. We have shown that the peptide derivative of PALO is selectively taken up by gut cells via the peptide permease and is released intracellularly as the free inhibitor. When administered in drinking water to 6-wk-old rat pups on an arginine-deficient diet, serum citrulline was reduced from 85 +/- 4.2 to 44 +/- 2.2 microM and arginine from 240.1 +/- 19.0 to 52.1 +/- 4.1 microM. Ornithine increased from 100 +/- 6.2 to 273.5 +/- 21.3 microM. Addition of 0.1 mM Gly-Gly-PALO to drinking water caused a rapid and complete inhibition of growth in rats on arginine-deficient diets, and this growth inhibition could be partially prevented by simultaneous administration of 1% (wt/wt) arginine to the diet and completely prevented with 1% (wt/wt) citrulline. The specificity of the effects of Gly-Gly-PALO on intestinal citrulline synthesis was shown by the inability of the drug to be taken up or to inhibit citrulline synthesis in isolated rat hepatocytes, and the oral administration of the drug had no effect on serum ammonia concentrations. The relative importance of endogenous synthesis of arginine compared with dietary arginine for growth was shown by the ability of Gly-Gly-PALO to inhibit the growth of rats maintained on standard laboratory chow containing normal levels of arginine.
Substance P: a potent inhibitor of the canine small intestine in vivo
Authors: Fox J. E. , Daniel E. E.
Published: December 2017

Intra-arterially administered substance P inhibited neurally activated contractions of the circular muscle of canine small intestine in vivo (lowest effective dose approximately 10(-13) mol). Excitation of intestine required higher (10(-10) mol) doses. The inhibitory effect required functioning nerves, since tetrodotoxin treatment eliminated it. However, inhibition of neurogenic contraction by substance P was unaffected by nicotinic or opiate receptor antagonists or by catecholamine depletion but was reduced by a selective substance P antagonist. Since the inhibition by substance P was also greatly reduced by treatment with atropine or pirenzepine and acetylcholine given intra-arterially produced a similar inhibitory response, stimulation of release of acetylcholine to inhibitory muscarinic receptors on nerves appeared to be the mechanism of this action. Direct smooth muscle effects were ruled out; substance P did not inhibit contractions to intra-arterial acetylcholine or those following tetrodotoxin. In vitro in ileal strips, no inhibition by substance P of any contractile response was found. We propose that the local release of substance P into the myenteric plexus produces inhibition and suggest that this constitutes a physiological function of the neuropeptide. This action may be absent in vitro.
Waxing and waning of slow waves in intestinal musculature
Authors: Suzuki N. , Prosser C. L. , DeVos W.
Published: December 2017

Electrical slow waves from cat or rabbit small intestine show more variability when recorded in vivo than in vitro. One pattern of variation is waxing and waning of amplitude, or "spindling," during which two rhythms of slightly different frequency come in and out of phase. Fourier power analyses of slow waves during spindles show two frequency peaks of slow waves differing by 0.4-5.0 waves/min and corresponding to measured spindle durations of 12-150 s. Spindles can be induced in vitro in rabbit intestine by K depolarization of approximately 15 mV. Histograms of intracellular recordings of slow nonspindling waves show variation of 0.5-1.0 s on either side of a mean slow wave duration. Spindles are abolished by treatments that reduce electrical coupling between cells, e.g., hypertonic sucrose or lowered pH, but changes in calcium do not alter spindles. Simultaneous recordings by two electrodes in the longitudinal axis show synchrony of spindles at 2- to 3-mm but not at 5-mm separation and synchrony circumferentially to the opposite side of a segment. Contractions, both in vivo and in vitro, correspond with electrical spindles in amplitude. Spindle durations were significantly shorter in vivo than in vitro, indicating a significantly greater difference in vivo in the competing frequencies at the point of recording (P less than 0.01). Three conditions favoring waxing and waning are slight depolarization, variation in slow wave frequency at a point, and electrotonic coupling between muscle fibers. Spindles provide for rhythms of contractions of a 1- to 2-min period.
Salivary response to food in humans and its effect on gastric acid secretion
Authors: Richardson C. T. , Feldman M.
Published: December 2017

The purpose of these studies was to determine the amount of saliva secreted in response to food in humans and to evaluate the effect of saliva on postprandial gastric acid secretion. Subjects chewed and spat out an appetizing steak and french-fried potato meal (modified sham feeding), with the increase in the weight of the meal during sham feeding taken to represent salivary secretion. Mean salivary flow rose from basal rates of 37.1 ml/h to 167.3 ml/h during modified sham feeding (P less than 0.001). Chewing gum increased salivary secretion to approximately the same extent as modified sham feeding, whereas chewing on plastic tubing caused a much smaller increase in salivary flow. Intravenous infusion of bethanechol (50 micrograms . kg-1 . h-1) was approximately half as potent as modified sham feeding or gum chewing in stimulating salivary flow. The salivary response to sham feeding was completely blocked by 15 micrograms/kg intravenous atropine. Salivary secretion increased approximately 20 ml/h when a 700-ml amino acid meal was infused directly into the stomach (P less than 0.01), whereas gastric distension with 700 ml saline had no effect. These findings suggested that food in the stomach or upper small intestine may activate a reflex or release a hormone into the circulation that augments salivary flow. Although intravenous gastrin-17 infusion had no effect on salivary flow, somatostatin-14 infusion increased salivary flow 15 ml/h (P less than 0.02). Saliva contained approximately 2,000 pg/ml immunoreactive urogastrone, an inhibitor of acid secretion when administered parenterally.(ABSTRACT TRUNCATED AT 250 WORDS)
Dose-response effects of indomethacin and PGE2 on electromechanical activity of in vivo rabbit ileum
Authors: Koch K. L. , Dwyer A. , Jeffries G. H.
Published: December 2017

We determined dose-response characteristics of indomethacin and prostaglandin E2 on the myoelectric activity in ileum of anesthetized New Zealand White rabbits. Monopolar electrodes and an intraluminal saline-filled catheter were used to simultaneously record electrical and mechanical activity. Thirty minutes after injection of 3.0, 5.0, and 10.0 mg/kg indomethacin, the percentage of slow waves with action potentials increased significantly from 10% to over 80%; at 60 min action potential activity decreased but remained dose dependent and significantly greater than controls. Action potential activity correlated with phasic increases in intraluminal pressure. Low-dose indomethacin (1.5 mg/kg) did not significantly alter action potential activity. Action potential activity induced by indomethacin (5 mg/kg) decreased dose dependently after infusion of prostaglandin E2 (PGE2, 1-28 micrograms/kg). In summary, dose-dependent action potential activity was induced by indomethacin and reversed by PGE2. Endogenous inhibitory prostaglandins (PGE2 or others) appear to modulate activity of specific excitatory neuromuscular circuits in in vivo ileum.
Anionic basis of fluid secretion by rat pancreatic acini in vitro
Authors: Seow K. T. , Lingard J. M. , Young J. A.
Published: December 2017

Acinar secretion was studied in the caerulein-stimulated perfused rat pancreas. Unstimulated glands secreted at a mean basal rate of 1.1 microliters X g-1 X min-1 (SD = 0.74), which was not altered by perfusate anion substitution or by transport-blocking drugs. Caerulein evoked a maximum response (6.8 microliter X g-1 X min-1, SE = 0.36, n = 8) at a concentration of 18 pmol/l. Replacement of perfusate bicarbonate with either chloride or acetate did not significantly alter the stimulated secretory rate. In contrast, replacement with acetate of either chloride alone or chloride and bicarbonate reduced the rate of stimulated secretion by 75-80%, and replacement with isethionate abolished the response altogether. In glands perfused with solutions containing chloride but not bicarbonate, furosemide (10(-5) M), 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS, 10(-4) M), amiloride (10(-4) M), and methazolamide (10(-4) M) all reduced the secretory response by more than 70%. When bicarbonate was included in the perfusate, the inhibitory effects for the same doses of blockers were much less, and except for methazolamide the same level of maximum inhibition was obtained when the blocker doses were increased 10-fold. The results suggest that rat pancreatic acini utilize a different secretory mechanism from the sodium chloride-carrying symport postulated to be most important in rat mandibular glands. The simplest model to explain our results would involve paired, basolateral antiports for Na-H and Cl-HCO3 exchange. We cannot exclude the presence of a Na-Cl symport, but if present, its role appears to be minor.
Effects of viscosity and fluid outflow on postcibal gastric emptying of solids
Authors: Meyer J. H. , Gu Y. , Elashoff J. , Reedy T. , Dressman J. , Amidon G.
Published: December 2017

It is known that the food-filled stomach retains large spheres or pieces of food, allowing the passage of food particles or of plastic spheres with diameters mainly below 2 mm. We have recently shown that spheres having densities greater or less than water emptied from the food-filled canine stomach more slowly than spheres of the same diameter with a density of 1. Thus, hydrodynamics seem to govern gastric emptying of spheres. The present studies were undertaken to determine how altering other hydrodynamic factors, viscosity and velocity of fluid outflow, might affect gastric sieving. Ten mongrel dogs were prepared with chronic duodenal fistulas, which allowed collecting and measuring of emptied spheres and food. The dogs were fed a standard meal of 75 g of steak plus 25 g of 99mTc-labeled chicken liver. Immediately afterward, 50 3.2-mm Teflon spheres were instilled into the stomachs along with 200- or 800-ml volumes of saline or saline plus guar (a viscous polysaccharide). Whether 200- or 800-ml volumes were instilled, the guar significantly sped the emptying of the spheres. Fluid outflow was twice as fast after the 800-ml instillates, but the faster outflow with the 800 ml of saline did not speed emptying of spheres. With the guar instillates, the faster outflow slightly sped the emptying of the spheres and significantly increased the diameter of emptied particles of 99mTc-labeled chicken liver. We conclude that meal viscosity significantly affects gastric sieving.
Localization of chloride secretion in rabbit colon: inhibition by anthracene-9-carboxylic acid
Authors: Horvath P. J. , Ferriola P. C. , Weiser M. M. , Duffey M. E.
Published: December 2017

The substituted aromatic compound anthracene-9-carboxylic acid (A-9-C) was used to inhibit active Cl- secretion by the epithelium of short-circuited rabbit distal colon. Tissues were mounted in Ussing chambers and stimulated to secrete Cl- by the addition of 1 mM dibutyryl adenosine 3',5'-cyclic monophosphate to the serosal bath. Results of 36Cl-flux measurements showed that the addition of 0.1 mM A-9-C to the mucosal bath inhibited Cl- secretion by 48%. The site of Cl- secretion was determined by using conventional micro-electrodes to show that the cells of the crypt regions, and not the surface epithelial cells, responded to A-9-C by an increase in apical membrane fractional resistance from 0.75 to 0.80 and a hyperpolarization of the apical membrane from -64 to -68 mV (P less than 0.05). The sulfhydryl reagent dithiothreitol was added to the mucosal tissue bath to remove the mucus produced by goblet cells of the crypt regions of these tissues. The time for maximal inhibition of Cl- secretion by A-9-C was decreased from 30 to 15 min by removal of the mucus barrier. The effects of A-9-C on the crypt cells, as well as the effect of mucus on the inhibitory action of this compound, demonstrate that the crypt region is the site of Cl- secretion.
Interaction of flow and resistance in maintenance of portal hypertension in a rat model
Authors: Sikuler E. , Groszmann R. J.
Published: December 2017

To clarify the roles that portocollateral resistance ("backward-flow" theory) and portal flow ("forward-flow" theory) play in maintaining chronic portal hypertension, we studied, in a rat model with prehepatic portal hypertension, the hemodynamic changes that occur when portocollateral resistance is reduced and high portal venous inflow is maintained. In 30 portal-hypertensive rats the constriction around the portal vein was removed 4 days after induction of portal hypertension, 30 rats were used as portal vein-constricted controls, and 30 additional rats were subjected to a sham operation. The removal of the ligature constricting the portal vein was followed by an immediate decrease in portal pressure (from 16.3 +/- 0.8 to 9.6 +/- 0.8 mmHg, P less than 0.001). Two days after the ligature removal, hyperdynamic circulation was still evident and was characterized by a decreased splanchnic arteriolar resistance and an increased portal venous inflow. The coexistence of high portal venous inflow and normal portal pressure indicates that high portal venous inflow per se is not sufficient to produce an increase in portal pressure when it faces a low-resistance vascular bed. We conclude that portal hypertension is induced by the interaction of an abnormally high portal venous inflow and high resistance offered to the flow by the portocollateral vessels. Neither the forward-flow theory nor the backward-flow theory can be applied solely to explain the increased portal pressure.
Contraction pattern of opossum gallbladder during fasting and after feeding
Authors: Takahashi I. , Kern M. K. , Dodds W. J. , Hogan W. J. , Sarna S. K. , Soergel K. H. , Itoh Z.
Published: December 2017

Our major aims in this study were to determine in unanesthetized opossums the gallbladder volume, pressure, and tone during fasting as well as after feeding, model the kinetics of changes in gallbladder volume, and correlate gallbladder contractility with concurrent spike burst activity in the upper gastrointestinal tract and sphincter of Oddi (SO). In 10 animals, we implanted electrodes on the gastric antrum, duodenum, SO, and jejunum. An indwelling catheter monitored gallbladder pressure and volume. In two animals, a force transducer sutured to the gallbladder wall monitored gallbladder tone. In each animal, fasting migrating myoelectric complexes (MMCs) were recorded in the stomach and small bowel. Cyclic changes in SO spike bursts occurred in synchrony with the MMCs. During fasting, gallbladder pressure, tone, and volume showed cyclic variations. During the second half of the duodenal MMC cycle, the gallbladder exhibited phasic as well as tonic contractions associated with net gallbladder emptying, whereas during the first half of the cycle the gallbladder relaxed and refilled. Minimal gallbladder volume during the MMC cycle averaged 4.8 +/- 0.7 (SE) ml compared with a maximal volume of 7.0 +/- 0.9 ml. Decreases in gallbladder volume occurred as an exponential function, whereas increases in gallbladder were linear. After feeding, the gallbladder underwent a sustained tonic contraction, without superimposed phasic contractions. Decreases in gallbladder volume occurred exponentially to a residual volume of 2.0 +/- 0.5 ml. Net postprandial gallbladder emptying was maximal by 40 min; then the volume remained unchanged for 2-3 h.(ABSTRACT TRUNCATED AT 250 WORDS)
Intestinal phosphate absorption: influence of vitamin D and non-vitamin D factors
Authors: Lee D. B. , Walling M. W. , Brautbar N.
Published: December 2017

The transport of inorganic phosphate (P) was measured in the absence of electrochemical gradients across rat jejunum in vitro. Active P absorption was demonstrated in young, vitamin D-deficient (-D) rats, whereas active P secretion was found in normal, non-vitamin D-deficient adult rats, suggesting regulation of intestinal P transport by age-dependent but vitamin D-independent mechanisms. 1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] stimulated mucosal-to-serosal P flux (Jm----s) without affecting serosal-to-mucosal P flux (Js----m), causing further increases in net P absorption (Jnet) in -D rats and reduction in net P secretion in normal adult rats, confirming a previously described role of this hormone on P absorption. We then examined the effect of increasing extracellular (buffer) P concentration [P] on this 1,25(OH)2D3-stimulated active P absorption in jejunum from -D rats. At [P] of 0.024, 0.24, and 2.4 mM, 1,25(OH)2D3 consistently stimulated Jm----s without affecting Js----m, causing an increment in Jnet. At 7.5 mM [P], however, this Jm----s stimulatory effect of 1,25(OH)2D3 was no longer observed. Moreover, at this [P] the Js----m exceeded Jm----s in both -D and 1,25(OH)2D3-repleted rats, converting the active P absorption into active P secretion in both treatment groups. These observations suggest the participation of local mechanisms, such as the ambient [P] of the transporting enterocytes, in the regulation of intestinal P absorption. Finally, the influence of dietary P deprivation on P absorption was studied in -D rats, with or without either vitamin D3 or 1,25(OH)2D3 repletion.(ABSTRACT TRUNCATED AT 250 WORDS)
Isolated canine ileal mucosal cells in short-term culture: a model for study of neurotensin release
Authors: Barber D. L. , Buchan A. M. , Walsh J. H. , Soll A. H.
Published: December 2017

We have developed a new technique for maintaining isolated enteric mucosal cells containing neurotensinlike immunoreactivity (NTLI) in short-term culture to determine the regulation of NTLI release. Collagenase-dispersed ileal mucosal cells, separated by centrifugal elutriation, were enriched for NTLI-containing cells as determined by immunohistochemistry and radioimmunoassay. Bombesin (BBS) rapidly stimulated NTLI release from freshly isolated cells. However, studies with freshly isolated cells were limited by high, unstable basal release measurements and rapid degradation of added [3H]neurotensin-(1-13). A culture system of elutriator-enriched NTLI cells was therefore developed. After 48 h NTLI cells selectively adhered to the collagen substrate and constituted 40% of the viable cells in culture. The morphology of NTLI cells in culture closely resembled neurotensin cells in intestinal tissue sections, with a secretory granule diameter of 292 +/- 14 nm. Bombesin stimulated a dose-dependent increase in NTLI secretion over 120 min. In these cell cultures, degradation of added [3H]-neurotensin-(1-13) was minimal over 120 min. High-pressure liquid chromatographic analysis of culture supernatants characterized neurotensin-(1-13) as the primary molecular form of neurotensin released in response to BBS stimulation. In conclusion, we have established a primary culture of enteric neurotensin cells that provides a model for studying the regulation of peptide release. Bombesin stimulation of NTLI release verified the functional responsiveness of this isolated cell system.
Secretion of pyruvate and lactate in pancreatic juice induced by acetazolamide or secretin
Authors: Kuroshima T. , Himeno S. , Kurokawa M. , Tsuji K. , Tarui S.
Published: December 2017

In vivo studies using pentobarbital sodium-anesthesized dogs were performed to investigate whether a transport pathway for pyruvate and lactate is present in the exocrine pancreas. Concentrations of both acids were measured in peripheral blood and pancreatic juice before and after intravenous 15-min administration of 2.25 mmol/kg DL-lactate, superimposed on continuous intravenous infusion of 3 U X kg-1 X h-1 secretin. The concentration ratio of lactate to pyruvate in pancreatic juice was found to be approximately 1, a lower value than found in other tissues or body fluids. D-lactate, not detected in either blood or juice during basal periods, rapidly appeared in both fluids in parallel with the physiological isomer L-lactate, after the infusion of DL-lactate. Further addition of acetazolamide or a high dose of secretin caused a marked secretory response of pyruvate and lactate with no increase in juice bicarbonate levels. We conclude that these acids can be transported from blood to lumen when the transmembrane pH gradient across the duct cell membranes is augmented by stimulants via a proton pump mechanism involving a CO2-HCO3-buffer system.
Intestinal calcium transport in the spontaneously hypertensive rat: response to calcium depletion
Authors: Schedl H. P. , Miller D. L. , Horst R. L. , Wilson H. D. , Natarajan K. , Conway T.
Published: December 2017

We previously found intestinal Ca2+ transport to be lower in the spontaneously hypertensive (SH) as compared with the Wistar-Kyoto control (WKY) rat. These animals were fed a relatively high (1%) Ca2+ diet, and the concentration of 1 alpha,25-dihydroxycholecalciferol [1 alpha,25(OH)2D3] in serum was the same in both groups. In the present experiment we tested the possibility that the lower Ca2+ transport in the SH rat was the result of unresponsiveness to 1 alpha,25(OH)2D3. We fed diets high and low in Ca2+ and measured serum 1 alpha,25(OH)2D3 and Ca2+ transport. Serum 1 alpha,25(OH)2D3 increased in response to Ca2+ depletion at both 5 and 12 wk in both the WKY and SH rat. With high-Ca2+ diet, Ca2+ transport was lower in SH than in WKY when studied 1) in vitro in duodenum at 5 wk of age, and 2) in vivo in proximal and distal small intestine at 12 wk of age. Ca2+ transport increased in SH in response to Ca2+ depletion, but not in WKY, except in distal small intestine in vivo at 12 wk. In summary, although Ca2+ transport is lower in the SH as compared with the WKY rat when vitamin D activity is basal through feeding a high-Ca2+ diet, Ca2+ transport increases in the SH rat in response to the increase in 1 alpha,25(OH)2D3 produced by feeding a low-Ca2+ diet. We conclude that 1) the vitamin D-regulated component of mediated Ca2+ transport is intact in the SH rat and is unrelated to hypertension, and 2) mediated Ca2+ transport under basal conditions, i.e., nonvitamin D-regulated, differs in the SH and WKY rats and may be related to hypertension.
Dehydroascorbic acid and ascorbic acid transport systems in the guinea pig ileum
Authors: Bianchi J. , Wilson F. A. , Rose R. C.
Published: December 2017

The transport properties of dehydroascorbic acid and ascorbic acid in membrane vesicle preparations of guinea pig ileum were evaluated. Na-dependent transport of ascorbic acid in the brush-border membrane was confirmed, and an Na-independent mechanism was found in the basolateral membrane. The electrically neutral oxidized form of vitamin C is transported by an Na-independent mechanism at both cell surfaces. Transport of each substrate is saturable and exhibits cis-inhibition and trans-stimulation in the presence of structural analogues. Additional studies on ascorbate metabolism will be necessary to support a comprehensive model of intestinal handling of vitamin C.
Role of ethanol metabolism in the ethanol-induced increase in splanchnic circulation
Authors: McKaigney J. P. , Carmichael F. J. , Saldivia V. , Israel Y. , Orrego H.
Published: December 2017

In this study we report the effect on splanchnic hemodynamics of acute oral ethanol at doses ranging from 0.25 to 4.0 g/kg body wt. Flows were determined by use of a radioactive microsphere technique. Ethanol was found to increase portal blood flow by 23-57%. In awake rats this increase reached a plateau at the 0.5 g/kg dose. In ketamine-anesthetized rats, the increase was observed only at doses of 3.0 g/kg or more, with the response at doses of 0.5, 1.0, and 2.0 g/kg being suppressed by ketamine. Inhibition of alcohol dehydrogenase by intra-arterial administration of 4-methylpyrazole resulted in suppression of the liver blood flow increase after ethanol was administered to awake animals. Ethanol in the range of doses studied did not result in changes in blood glucagon levels. Rats fed ethanol-containing diets for 4 wk and withdrawn for 18 h had the same response to acute oral ethanol as did naive rats. It is suggested that ethanol metabolism mediates the effects of ethanol on splanchnic blood flow. An increase in splanchnic blood flow when concurrent with an increase in liver O2 consumption induced by ethanol might protect the liver from hypoxic damage.
Ca2+-, phorbol ester-, and cAMP-stimulated enzyme secretion from permeabilized rat pancreatic acini
Authors: Kimura T. , Imamura K. , Eckhardt L. , Schulz I.
Published: December 2017

Enzyme secretion from the exocrine pancreas is stimulated by receptor-activated breakdown of phosphatidylinositol 4,5-bisphosphate and consequent rise of both inositol 1,4,5-trisphosphate (IP3) and diacylglycerol, which leads to Ca2+ release and to activation of protein kinase C, respectively. Another way involves receptor-mediated stimulation of adenylate cyclase and consequent rise of cAMP and activation of protein kinase A. In the present work we have studied direct stimulation, inhibition, and mutual interaction of these pathways on enzyme secretion from isolated rat pancreatic acini that had been permeabilized by treatment with saponin or digitonin. The data were compared with those obtained in isolated intact acini. The data show that with increasing free Ca2+ concentrations greater than 10(-6) M protein release increases in "leaky" but not in "intact" cells and is maximal at approximately 10(-3) M, increasing about twofold compared with that in the absence of Ca2+. In the presence of the acetylcholine analogue carbachol, this effect of Ca2+ is enhanced by about threefold in leaky cells and is also present in intact cells to a similar extent. cAMP and its analogues, dibutyryl cAMP (dbcAMP) and 8-bromo-cAMP stimulate protein release by about twofold in the presence of Ca2+ in leaky cells. In intact acini cAMP has no effect, and cAMP analogues stimulate enzyme secretion by about twofold in some but not all experiments. Similarly, forskolin, an activator of adenylate cyclases and inhibitors of cyclic nucleotide-dependent phosphodiesterases, such as 3-isobutyl-1-methylxanthine (IBMX) and R0 201724, stimulate protein release in permeabilized acini. The Ca2+-binding protein calmodulin has no effect on enzyme secretion, whereas the calmodulin antagonist trifluoperazine dihydrochloride stimulates protein release in leaky but not in intact acini. The activator of protein kinase C, 12-O-tetradecanoylphorbol 13-acetate (TPA) stimulates protein release in a Ca2+-dependent manner and enhances cAMP-induced secretion. The effects of carbachol, TPA, cAMP, and a combination of both TPA and cAMP are inhibited by the polyamine spermine in permeabilized cells. Spermine has no effect on carbachol-induced enzyme secretion in intact cells. The data suggest that enzyme secretion from pancreatic acinar cells is mediated by cAMP protein kinase A and by Ca2+ phospholipid protein kinase C in a Ca2+-dependent way and that interaction occurs between both pathways.
Formation and transport of chylomicrons by enterocytes to the lymphatics
Authors: Tso P. , Balint J. A.
Published: December 2017

Digestion of triglyceride in the intestine results in the production of 2-monoglyceride and fatty acid. Phosphatidylcholine is hydrolyzed in the lumen to form lysophosphatidylcholine before its absorption. These digestion products are absorbed by the enterocytes through simple diffusion. In contrast, cholesterol absorption seems specific and is energy dependent. After entry into the enterocytes, these lipid digestion products migrate to the endoplasmic reticulum. Both fatty acid-binding protein and sterol carrier protein may be involved in the intracellular transport of fatty acid and cholesterol, respectively. Through predominantly the monoglyceride pathway, monoglycerides and fatty acids are resynthesized to form triglyceride in the endoplasmic reticulum. The lipid droplets, coated with cholesterol, phospholipid, and apolipoproteins, are then further processed in the Golgi apparatus before being released by the enterocytes through exocytosis. As yet, little is known of the factors regulating the formation and release of these chylomicrons by the enterocytes. Although apolipoprotein B is a prerequisite for the formation of chylomicrons, the question of whether its supply is rate limiting for chylomicron formation remains to be demonstrated. Other factors that may play a role in chylomicron formation are luminal phospholipid supply, Ca2+, and microtubules. Chylomicrons and very low-density lipoproteins are probably produced by the enterocytes via different pathways. For example, Pluronic L-81, a hydrophobic surfactant, affects only chylomicron formation and has little effect on very low-density lipoprotein production. The movement of chylomicrons from the intercellular space through the basement membrane to the lamina propria is not fully understood. Once inside the lamina propria, the movement of chylomicrons is probably by diffusion and is greatly facilitated by interstitial hydration; thus the lymphogogic effect of fat absorption may serve an important function for the transfer of chylomicrons from the enterocytes to the lacteal.
Carotid sinus baroreceptor modulation of fluid transport and blood flow in the feline jejunum
Authors: Sjovall H. , Butcher P. , Biber B. , Martner J.
Published: December 2017

Carotid sinus baroreceptor control of jejunal fluid transport and vascular resistance was studied in chloralose-anesthetized cats. The carotid sinuses were isolated and perfused with blood from the femoral arteries. The aortic nerves were divided. In an isolated jejunal segment we measured net fluid transport rate, transmural potential difference (PD), and blood flow at a constant perfusion pressure of 75 mmHg. Carotid sinus pressure (CSP) was increased to 200–250 mmHg and was then lowered, in steps of approximately 25 mmHg, down to 50 mmHg. In the pressure interval from 90 to 200 mmHg, decreases in CSP increased jejunal vascular resistance and fluid absorption rate and decreased PD. In the interval from 50 to 90 mmHg, decreases in CSP increased vascular resistance and decreased PD but did not affect net fluid absorption rate. The results indicate that changes in baroreceptor activity may reflexly influence both vascular resistance and fluid transport rate in the feline jejunum, possibly via separate sympathetic mechanisms.