bluuebunny/crossref_metadata_2025 huggingface dataset:
Vasoactive intestinal polypeptide provokes acetylcholine release from the myenteric plexus
Authors: Kusunoki M. , Tsai L. H. , Taniyama K. , Tanaka C.
Published: December 2017

Effects of vasoactive intestinal polypeptide (VIP) on the release of acetylcholine (ACh) from longitudinal muscle strips with myenteric plexus (LM) preparations were examined in the guinea pig small intestine. VIP (10(-10) to 10(-6) M) induced a concentration-dependent contraction of LM preparation. The VIP-induced contractions seem to be related to three components, the scopolamine-sensitive, the scopolamine-insensitive, the tetrodotoxin-sensitive, and the tetrodotoxin-insensitive contractions. VIP (10(-10) to 10(-6) M) induced a concentration-dependent increase in the release of [3H]ACh from LM preparations preloaded with [3H]choline. The VIP-evoked [3H]ACh release was inhibited by removal of Ca2+ from the perfusion medium and by treatment with tetrodotoxin but not by scopolamine and hexamethonium. The spontaneous and VIP-evoked [3H]ACh release was not affected by phentolamine, propranolol, methysergide, diphenhydramine, cimetidine, bicuculline, or [D-Pro2, D-Trp7,9]substance P. The result demonstrates that VIP induces contractions of longitudinal smooth muscle directly and indirectly by the stimulation of both cholinergic neurons and noncholinergic excitatory neurons.
Effect of atropine on rat pancreatic secretory response to trypsin inhibitors and protein
Authors: Levan V. H. , Green G. M.
Published: December 2017

The effect of atropine on the exocrine pancreatic secretory response to intestinally infused trypsin inhibitor and protein in conscious rats was investigated. Bile and pancreatic juice were collected and continuously returned to the intestine throughout all experiments. Ovomucoid trypsin inhibitor (OMTI) was infused at 1, 3, 6, 12, and 30 mg/h id, simultaneously with intravenously infused atropine (100 micrograms X kg-1 X h-1) or 0.15 M NaCl. Casein was infused at 300 mg/h id with or without intravenous atropine. Atropine inhibited basal pancreatic protein and fluid secretion 65.7 and 24.7%, respectively. Atropine had no effect on incremental (above basal) pancreatic protein and fluid output during infusion of maximally effective doses of OMTI (12 and 30 mg/h) and increased the incremental responses to submaximal doses of OMTI and to casein. The results are consistent with the hypothesis that cholecystokinin mediates negative feedback regulation by luminal proteases and that cholinergic mechanisms are not directly involved in this regulatory mechanism.
Phosphate transport across rat jejunum: influence of sodium, pH, and 1,25-dihydroxyvitamin D3
Authors: Lee D. B. , Walling M. W. , Corry D. B.
Published: December 2017

Inorganic phosphate (Pi) transport in intact, rat jejunal epithelium was measured in vitro under short-circuited conditions. Transepithelial net absorptive Pi flux increased linearly with increases in extracellular sodium concentration ([Na]) up to 144 mM. Transmucosal border Pi influx, in contrast, displayed a biphasic Na dependency. Pi influx increased as [Na] was raised from 0 to 100 mM. A further increase in [Na] to 144 mM caused unanticipated reduction in Pi influx. The reason for this dissociation between transmucosal border influx and transepithelial absorptive flux is not clear. We then examined the effect of changes in extracellular pH on Pi influx. Reduction in pH from 7.4 to 6.0 was associated with 150% increase in Pi influx, an observation consistent with the reported reciprocal relation between intestinal brush-border membrane vesicles (BBMV) Pi uptake and extravesicular pH. In contrast to BBMV data, however, a smaller increase (50%) in mucosal Pi influx was noted in intact epithelium when pH was increased from 7.4 to 8.5. Under optimized conditions for Pi influx, i.e., [Na] = 90 mM and pH 6.0, the effect of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on Pi influx was measured. The total influx could be resolved into a saturable, Na-dependent and a nonsaturable, Na-independent component. 1,25(OH)2D3 stimulated the saturable component of Pi influx.
Convergence of sensory information from abdominal viscera in the rat brain stem
Authors: Appia F. , Ewart W. R. , Pittam B. S. , Wingate D. L.
Published: December 2017

This study was carried out to establish whether there was convergence of sensory information in the rat brain stem stimulated by physiological activation of gastric mechanoreceptors and hepatic glucoreceptors. Extracellular recordings were made from single neurons in the region of the dorsal vagal nucleus and nucleus of the solitary tract in the medulla. The responses of these neurons to gastric distension, hepatic portal vein perfusion of isotonic D-glucose, and hepatic portal vein infusion of isotonic saline were studied. Fifty-six neurons were studied; it was found that there was no significant difference in the proportion of neurons responding to gastric distension compared with the number responding to either form of hepatic stimulation. In 20 neurons (all 3 types of stimulation were tested on the same neuron), both excitation and inhibition were observed with both forms of visceral stimulation. Of the seven of these neurons that responded to hepatic portal vein infusion, four of them also had an input from gastric mechanoreceptors. Only three of the neurons that responded to hepatic stimulation showed a specific response to hepatic glucose perfusion; in the remainder a component of the response was due to the infusion of the volume itself. The results from these experiments have demonstrated an apparently weak functional synaptic projection carried by hepatic vagal afferents, particularly those responding to changes in portal glucose concentration, which may indicate a rather diffuse and nonspecific sensory system in the liver. These results have also demonstrated the convergence onto neurons in the brain stem of information from gastric and hepatic enteroceptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Calcium utilization by dispersed canine gastric smooth muscle cells
Authors: Collins S. M.
Published: December 2017

Smooth muscle cells were isolated by collagenase digestion from the circular layer of the canine gastric corpus, and cell length was measured by image-splitting micrometry. Cells contracted following incubation with KCl, carbachol, and pentagastrin. While contraction induced by 40 mM KCl was inhibited by adding nitrendipine (10 nM) or by removing extracellular calcium and adding EGTA (2 mM), the contraction induced by carbachol (10 pM) was not affected by these measures. Nitrendipine partially inhibited contraction induced by pentagastrin, and pentagastrin also contracted cells that had been depolarized by prior exposure to KCl and nitrendipine. Removing extracellular calcium and adding EGTA partially inhibited contraction induced by maximally (10 pM) or submaximally effective (0.3 pM) concentrations of pentagastrin but did not affect that induced by 300 pM pentagastrin. These results indicate that isolated smooth muscle cells utilize calcium for contraction by three distinct mechanisms. The extent to which each mechanism contributes to contraction depends on the nature of the stimulus and, in the case of pentagastrin, the concentration of the stimulating ligand.
Intestinal absorption of lithocholic acid sulfates in the rat: inhibitory effects of calcium
Authors: Kuipers F. , Heslinga H. , Havinga R. , Vonk R. J.
Published: December 2017

Sulfation of lithocholic acid has been proposed as a mechanism for elimination of this hepatotoxic bile acid from the body by accelerating its fecal excretion. However, quantitative data on the absorption characteristics of sulfated lithocholic acid conjugates in vivo are scarce. We studied the intestinal absorption of 14C-labeled glycolithocholic acid (GLC), taurolithocholic acid (TLC), and their 3 alpha-sulfate esters, SGLC and STLC, respectively. Studies were performed in unanesthetized rats with a permanent biliary drainage. At an intestinal infusion rate of 125 nmol/min, which is comparable to 7% of the normal biliary bile acid output in the rat, the absorption of sulfated lithocholic acid conjugates was delayed when compared with their unsulfated precursors but quantitatively only slightly reduced over a 24-h period: SGLC 90.9 +/- 3.6%, GLC 94.4 +/- 1.1%, STLC 84.4 +/- 3.0%, and TLC 94.2 +/- 2.1%. Urinary excretion of sulfated and unsulfated bile acids was similar and never exceeded 2% of the dose. SGLC absorption was dose dependent, was not altered by coinfusion of rat bile, and was only slightly reduced by a sixfold overdose of taurocholic acid. SGLC and STLC were excreted into bile largely unchanged in form. In contrast, GLC and TLC were extensively metabolized to more polar bile acids, predominantly to beta-muricholic acid conjugates. Replacement of NaCl in the infusion fluid by CaCl2 reduced the absorption of SGLC and STLC by 63 and 52%, respectively. This calcium effect was less pronounced for the unsulfated bile acids: GLC -22%, and TLC -19%. Absorption of taurocholic acid was unaffected by CaCl2.(ABSTRACT TRUNCATED AT 250 WORDS)
Evidence against luminal one-for-one Cl(-)-HCO-3 exchange in urodele small intestine
Authors: White J. F.
Published: December 2017

The ratio of Cl- absorbed to HCO3- secreted by the in vitro small intestine of Amphiuma was measured using 36Cl and titration. The aim was to estimate the stoichiometry and thereby elucidate the underlying transport mechanisms. For every mole of HCO3- secreted 1.8 mol of Cl- underwent net absorption. Indirect measures of net Cl- absorption and HCO3- secretion were validated. Several known and putative Cl- transport inhibitors were examined for their ability to inhibit the anion transport events. Disulfonic stilbenes [4-acetamido-4'-isothiocyanostilbene-2',2'-disulfonic acid and 4,4'-diisothiocyano-2,2'-disulfonate stilbene (DIDS)] and the diuretics piretanide and furosemide inhibited the Cl- absorptive flux (JClm----s) and simultaneously the HCO3- secretory flux (JHCO3-). The diuretics acetazolamide and bumetanide also reduced JHCO3- and JClm----s, although the latter effect was not statistically significant. The ratio of inhibition, delta JClm----s/delta JHCO3-, varied from 1.2 to 1.8 for the different inhibitors. The presence of Cl(-)-HCO3- exchange at the serosal membrane was deduced from the reduction of JClm----s and JHCO3- by serosally added stilbenes, the reduction of Cl- absorption when serosal Cl- was replaced (reduced Cl(-)-Cl- exchange), inhibition of the secretory-to-mucosal Cl- flux by serosal stilbenes, and enhancement of JHCO3- when serosal medium HCO3- was elevated. Addition of DIDS to the mucosal medium did not alter the secretory flux. The observations are not consistent with one-for-one exchange of Cl- for HCO3- at the mucosal membrane. Other possible mechanisms including rheogenic Cl- uptake in parallel with electrodiffusional efflux of HCO3- are discussed. The observed coupling ratio is compatible with a one-for-one exchange of Cl- for HCO3- at the serosal membrane.
Localization of vitamin D-dependent active Ca2+ transport in rat duodenum and relation to CaBP
Authors: Roche C. , Bellaton C. , Pansu D. , Miller A. , Bronner F.
Published: December 2017

Vitamin D-replete (+D) and vitamin D-deficient (-D) rats received by intraperitoneal injection varying amounts of 1,25-dihydroxyvitamin D3, and 4 h (+D) or 9 h (-D) later everted duodenal sacs were prepared to evaluate active calcium transport, i.e., the amount of calcium found in the serosal fluid. At the same time, duodenal calcium-binding protein (CaBP) content was measured. Calcium transport was a close positive function of CaBP content. It was not detectable when CaBP content was zero and increased linearly without plateauing as CaBP content increased to 100 nmol calcium bound/g mucosa. Trifluoperazine (TFP) inhibited active calcium transport in a concentration-dependent manner. Experiments using vesicles prepared from brush-border or basolateral membranes indicated that TFP inhibited the calcium-extrusion process, with virtually no effect on calcium entry. It is concluded that vitamin D exerts its major regulation of active calcium transport in the rat duodenum via CaBP on transport steps beyond brush-border entry.
Effects of glucose-insulin-potassium on intestinal hemodynamics and substrate utilization during endotoxemia
Authors: Lang C. H. , Alteveer R. J.
Published: December 2017

This study examined the effects of endotoxin on small intestinal hemodynamics and metabolism with and without an infusion of glucose-insulin-potassium (GIK). Glucose uptake and lactate release were determined by arteriovenous differences across a segment of canine ileum, which was vascularly isolated in vivo, and by the direct measurement of intestinal blood flow. Free fatty acid (FFA) utilization by intestinal tissue was assessed by the constant infusion of albumin-bound [14C]palmitate and [3H]oleate. Endotoxemic dogs showed a sustained reduction of mean arterial blood pressure (MABP) and intestinal blood flow. In contrast, endotoxemic dogs infused with GIK demonstrated a decreased intestinal vascular resistance and an increased blood flow (two-fold), whereas MABP was transiently improved. Intestinal glucose uptake was not different from control values in endotoxemic animals; however, a sixfold increase was seen in shocked dogs treated with GIK. The endotoxin-induced increase in the plasma lactate concentration and intestinal lactate release was similar between dogs infused with saline or GIK. After endotoxin, the arterial FFA concentration remained unchanged and whole-body FFA turnover was decreased. FFA uptake by the gut was reduced, but FFA oxidation was not altered. Similar changes in FFA metabolism were seen in endotoxemic animals infused with GIK. The metabolic pattern after endotoxin suggests an elevated rate of aerobic glycolysis by the gut that increases the availability of lactate to the liver. Compared with saline-infused endotoxemic animals, GIK produced an elevation in glucose uptake without a further increase in lactate output, suggesting an increased storage of glucose by this tissue.
Mechanism of inhibition of glutathione efflux by methionine from isolated rat hepatocytes
Authors: Aw T. Y. , Ookhtens M. , Kaplowitz N.
Published: December 2017

We studied mechanism of inhibition of glutathione (GSH) efflux by methionine with freshly isolated rat hepatocytes. Inhibition was specific for L-methionine and was not due to changes in membrane potential or cell volume. Methionine (100 microM) inhibited GSH efflux from cells having 20-60 nmol GSH/10(6) cells. Inhibition was overcome in cells with greater than 75 nmol GSH/10(6) cells. Kinetics of control and inhibited efflux were sigmoidal saturable and were fitted well with the Hill model having three cooperative binding per transport sites. Vmax was the same for both cases (0.24 +/- 0.013 nmol X min-1 X 10(6) cells-1), implying that the inhibition was competitive. Apparent Km of efflux was 3.3 +/- 0.20 mM for controls but was shifted to 5.6 +/- 0.14 mM (P less than 0.01) in the presence of 100 microM methionine. Kinetic analysis of the inhibition by varying concentrations of methionine estimated Ki = 61.3 +/- 6.0 microM and n = 1.2 +/- 0.07, suggesting involvement of a single inhibition site. Methionine uptake was independent of GSH concentration, and blocking its uptake with 2-amino-2-norbornanecarboxylic acid did not affect inhibition. When methionine-preloaded cells were resuspended in methionine-free buffer, GSH efflux rapidly returned to control levels, whereas digitonin-releasable cellular methionine remained nearly constant. Thus, inhibition appeared to be exerted from outside the cell, possibly through an allosteric mechanism. A consequence of inhibition of GSH efflux by methionine was decreased uptake of cysteine equivalents from extracellular cystine.
Localization of intrahepatic portal vascular resistance
Authors: Lautt W. W. , Greenway C. V. , Legare D. J. , Weisman H.
Published: December 2017

The pressure drop from the portal vein to the vena cava occurs primarily across a postsinusoidal site localized to a narrow segment (less than 0.5 cm) of hepatic veins (roughly 1.5 mm diam) in the anesthetized cat. Portal venous pressure (PVP = 8.9 +/- 0.3 mmHg) and lobar hepatic venous pressure (LVP = 8.7 +/- 0.4 mmHg) are insignificantly different, and pressure changes imposed from the presinusoidal or postsinusoidal side are equally transmitted to both pressure sites. Several types of experiments were done to validate the LVP measurement. The portal vein, hepatic sinusoids, and hepatic veins proximal to the resistance site are all under a similar pressure. Previously reported calculations of hepatic vascular resistance are in error because of incorrect assumptions of sinusoidal pressure and localization of the portal resistance site as presinusoidal. Stimulation of hepatic sympathetic nerves for 3 min caused LVP and PVP to increase equally, showing that the increased "portal" resistance is postsinusoidal across the same region of the hepatic veins that was previously localized as the site of resistance in the basal state.
Greater taurodeoxycholate biotransformation during backward perfusion of rat liver
Authors: Baumgartner U. , Miyai K. , Hardison W. G.
Published: December 2017

Differing patterns of taurodeoxycholate (TDC) metabolism and biliary excretion were studied with a forward-and-backward perfusion model of the isolated rat liver. Livers were perfused with 8 microM TDC via either the portal vein (forward) or the hepatic vein (backward). Bile was collected, total bile acids measured enzymatically, and bile composition determined by high-pressure liquid chromatography and thin-layer chromatography. During backward perfusion 48% of infused TDC was metabolized to taurocholate (TC) and 22.0% to other minor TDC metabolites. During forward perfusion, however, only 16% of administered TDC was metabolized to TC and 6.5% to minor metabolites. Total bile acid output was similar for both forward and backward perfusions. The kinetics of biliary bile acid excretion also differed between forward and backward perfusion. The time necessary for 50% excretion of labeled TDC and its metabolites was 3.5 +/- 0.45 min during forward and 18 +/- 3.50 min during backward perfusion, a time difference of 14.5 min. The greater biotransformation of TDC during backward perfusion could be explained by its longer intracellular residence. The reason for the delayed excretion of TDC during backward perfusion is unknown.
Bicarbonate secretion by rabbit proximal colon
Authors: Sullivan S. K. , Smith P. L.
Published: December 2017

Stripped segments of proximal colon (1-6 cm distal to the ampulla caecalis coli) were studied in vitro in Ussing chambers under short-circuit conditions using the pH-stat technique. With glucose and HCO3-CO2 present in the serosal bathing solution only, proximal colon alkalinizes the luminal bathing solution at a rate of 2.1 +/- 0.2 mu eq X h-1 X cm-2 (n = 36). With HCO3-CO2 present in the luminal bathing solution alone, proximal colon does not significantly acidify or alkalinize the serosal bathing solution. Addition of glucose (10 mM) to the luminal bathing solution abolished luminal alkalinization. Removal of HCO3 and CO2 from the serosal bathing solution or replacement of O2 with N2 also abolished luminal alkalinization. Acetazolamide (0.1 mM) added to both bathing solutions did not alter the rate of luminal alkalinization. Ion-replacement studies revealed that the alkalinization process was highly dependent on the presence of Na in the bathing solutions and much less dependent on the presence of Cl. Furthermore, ouabain (0.1 mM) significantly reduced luminal alkalinization. As in rabbit ileum, serosal epinephrine (0.1 mM) did not alter luminal alkalinization but increased serosal alkalinization by a Na-dependent mechanism. These results suggest that luminal alkalinization results from a Na-dependent, active transcellular HCO3 transport process and that a Na-dependent HCO3 absorptive process is activated by adrenergic stimuli.
Effect of acute experimental colitis on rabbit colonic smooth muscle
Authors: Cohen J. D. , Kao H. W. , Tan S. T. , Lechago J. , Snape W. J.
Published: December 2017

The membrane potential and contractile activity of colonic circular smooth muscle from New Zealand White rabbits were studied after the production of acute experimental colitis. Colitis was induced in the distal colon by rectal infusion of formaldehyde solution, followed by an intravenous bolus of soluble immune complexes. Despite active mucosal inflammation, there are only occasional inflammatory cells in the muscularis. Electrophysiological studies on tissue from control rabbits and rabbits with colitis were performed using double sucrose gap and intracellular microelectrode techniques. The resting membrane potential was lower (-44 +/- 3 mV) in muscle from rabbits with colitis compared with control animals (-54 +/- 2 mV) (P less than 0.02). Amplitude of the electrotonic potential after a hyperpolarizing current pulse was decreased (P less than 0.05) and the time constant was shortened (P less than 0.01) in muscle from animals with colitis compared with normal animals. Amplitude (13.1 +/- 2.3 mV) and maximum rate of rise (0.24 +/- 0.06 V/s) of the spike potential, initiated by a depolarizing current pulse, were decreased in muscle from animals with colitis compared with muscle from healthy animals (P less than 0.001). Isometric tension generation after electrical and chemical depolarization of the membrane or bethanechol administration was decreased (P less than 0.001) in muscle from colitic animals. These studies suggest 1) membrane resistance and membrane potential are decreased in muscle strips from animals with colitis; and 2) there is a disturbance in the electrical and mechanical response of these tissues after stimulation.
Endogenous cholecystokinin drives gallbladder emptying in dogs
Authors: Shiratori K. , Watanabe S. , Chey W. Y. , Lee K. Y. , Chang T. M.
Published: December 2017

We investigated the effect of fat in the duodenum on the gallbladder emptying in seven dogs prepared with gastric, duodenal, and gallbladder cannulas. Gallbladder volume was measured at 15-min intervals, and venous blood samples were obtained at regular intervals for 2.5 h. Intraduodenal administration of Lipomul (pH 5.0, corn oil) in three different doses (1.1, 2.2, and 4.4 mmol/10 min) resulted in significant increases in gallbladder emptying in a dose-dependent manner (r = 0.8668, P less than 0.001). Likewise, the increase in integrated cholecystokinin (CCK) release in response to Lipomul was also dose dependent (r = 0.7334, P less than 0.001). A statistically significant correlation was found between integrated CCK release and gallbladder emptying in response to Lipomul (P less than 0.001). To determine the role of circulating endogenous CCK on gallbladder emptying effects of intravenous administration of proglumide and a rabbit anti-CCK serum on gallbladder emptying were studied. Gallbladder emptying was virtually abolished by the antiserum. Proglumide not only abolished the emptying but also increased gallbladder volume. Thus we conclude that in dogs the gallbladder emptying in response to fat in the upper small intestine depends on increased circulating endogenous CCK.
Xanthine oxidase and neutrophil infiltration in intestinal ischemia
Authors: Grisham M. B. , Hernandez L. A. , Granger D. N.
Published: December 2017

A growing body of experimental data indicates that reactive oxygen metabolites such as superoxide, hydrogen peroxide, and hydroxyl radical may mediate the mucosal injury produced by reperfusion of ischemic intestine. Xanthine oxidase has been proposed as the primary source of these reduced O2 species because pretreatment with xanthine oxidase inhibitors such as allopurinol or pterin aldehyde prevent postischemic mucosal injury. Another potential source of oxygen radicals is the inflammatory neutrophil. To ascertain whether neutrophils could play a role in the pathogenesis of ischemia-reperfusion injury in the small bowel we examined the effect of ischemia and reperfusion on neutrophil infiltration and tissue levels of reduced glutathione, superoxide dismutase, and catalase. Our studies demonstrate that reperfusion of ischemic intestines results in a dramatic increase (1,800%) in neutrophil infiltration and a concurrent loss of reduced glutathione and superoxide dismutase of 60 and 30%, respectively. Catalase activity was unaffected by ischemia-reperfusion. Pretreatment with allopurinol or administration of superoxide dismutase prevented the influx of neutrophils and retarded the drop in reduced glutathione levels. These results suggest a relationship among xanthine oxidase-generated oxy radicals, neutrophil extravasation, and mucosal damage. We propose that ischemia and reperfusion results in xanthine oxidase-generated, superoxide-dependent accumulation of inflammatory neutrophils in the mucosa where neutrophil-derived reactive oxygen metabolites mediate and/or exacerbate intestinal injury.
Relation between duodenal alkaline secretion and motility in fasted and sham-fed dogs
Authors: Konturek S. J. , Thor P.
Published: December 2017

A relation between duodenal myoelectric and motor activity and alkaline secretion has been investigated in conscious dogs under basal conditions and following vagal excitation with and without pretreatment with atropine or indomethacin. It was found that duodenal alkaline secretion shows typical periodicity in phase with the myoelectric or motor activity of the duodenum, reaching a peak during phase III and a nadir during phase I of the migrating motor complex (MMC). Sham feeding interrupted the motor and secretory MMC cycle and caused a prolonged increase in duodenal myoelectric or motor activity as well as a sudden and marked rise in duodenal alkaline secretion accompanied by a significant elevation in plasma gastrin and pancreatic polypeptide. Atropine and indomethacin abolished the motor and secretory duodenal cycles and reduced basal alkaline secretion significantly. Atropine abolished, whereas indomethacin increased duodenal myoelectric or motor activity during basal conditions and after vagal stimulation. Neither atropine nor indomethacin abolished sham feeding-induced duodenal alkaline secretion. We conclude that duodenal alkaline secretion fluctuates cyclically in phase with duodenal motility, vagal excitation results in a potent stimulation of duodenal motor and secretory activity, and the mechanism of vagally induced duodenal alkaline secretion is only partly cholinergic and does not involve endogenous generation of prostaglandins.
Distension pressure on subserosal and mesenteric lymph pressures of rat jejunum
Authors: Lee J. S.
Published: December 2017

Lymph pressure (Pl) in the subserosal lymphatics and mesenteric lymphatics was determined in the jejunum at various intraluminal distension pressures (DP). Pl in the subserosal lymphatics was approximately equal to DP, in the range of 3–100 mmHg, whether the intestine was in the basal state or during water absorption. At a DP of 0 mmHg, Pl was 1.5 +/- 0.1 mmHg. When DP was 3, 10, 20, 40, 70, or 100 mmHg, Pl was 2.9 +/- 0.2, 11 +/- 1, 23 +/- 1, 43 +/- 1, 71 +/- 2, or 102 +/- 2 mmHg, respectively. From these findings and other considerations it is inferred that Pl in the subserosal lymphatics could be similar to the tissue fluid pressure, which is apparently determined by DP due to compression of the intestinal wall. On the other hand, Pl in the mesenteric lymphatics was not affected by DP at all. When DP was in the range of 0–70 mmHg with free flow of lymph, mean Pl was 6-8 mmHg, and it was 23–28 mmHg during lymphatic obstruction. During pressure measurement, rhythmical contractions of these lymphatics occurred, which may be mainly responsible for the increase of Pl and propulsion of lymph as well.
Influence of phenobarbital on the hepatic handling of [3H]vitamin D3 in the dog
Authors: Gascon-Barre M. , Vallieres S. , Huet P. M.
Published: December 2017

The effect of phenobarbital (PB) on the hepatic handling of vitamin D3 (D3) and its metabolism to 25-hydroxyvitamin D3 [25(OH)D3] was studied in eight mongrel dogs. The hepatic uptake and clearance of [3H]D3 were evaluated by the multiple indicator-dilution curve technique, and the formation of [3H]25(OH)D3 was evaluated by sampling the hepatic effluent. The hepatic enzyme induction was assessed in six dogs by the 14CO2 breath excretion test. The results show that the hepatic uptake of [3H]D3 was not significantly affected but that its hepatic clearance was significantly increased during PB treatment. The [3H]25(OH)D3 production was increased during PB administration by a factor of 3–5 times over the pre- or post-PB period. Evaluation of the enzyme induction produced by PB revealed that two of the dogs studied had a blunted response to PB; furthermore, these dogs were the only animals that showed no increase in [3H]25(OH)D3 production during PB treatment and that in the presence of similar serum PB, endogenous 25(OH)D3 and 1,25-dihydroxyvitamin D3 pools, and hepatic uptake and clearance of [3H]D3. Strong positive correlation coefficients were observed between the breath excretion of 14CO2 and the [3H]25(OH)D3 production during PB treatment, whereas no correlation was present in the absence of PB. These observations show that, in most animals, PB is accompanied by an increased hepatic clearance of [3H]D3 and by an increased production of [3H]25(OH)D3. The data obtained during the present study also show that the response to PB is heterogeneous and that some animals escaped PB-mediated enzyme induction.(ABSTRACT TRUNCATED AT 250 WORDS)
Expression of amino acid and peptide transport systems in rat small intestine
Authors: Cheeseman C. I.
Published: December 2017

Quantitative autoradiography was used to measure the distribution of transport of leucine, lysine, and glycyl-L-leucine along the villus of the rat jejunum. A comparison was made between normal juvenile animals and ones maintained on a 5% protein isocalorific diet. Uptake of leucine, lysine, and glycyl-L-leucine was confined to the top 150 microns of the villus in control animals and initial expression of transport corresponded to a cell age of 32 h. The low-protein diet altered the distribution of transport in the same way for all three substrates, but although the position up the villus of the initial expression of transport was altered, transport always appeared in cells 32 h old. These data indicate that the age of intestinal epithelial cells is an important determinant of their ability to transport amino nitrogen. Transport kinetic data indicated that peptide uptake was initially elevated in response to the low-protein diet while free amino transport was depressed. It is concluded that a second locus of control determines the amount of transport expressed per individual cell.
Effects of micellar oleic acid on canine jejunal blood flow and neurotensin release
Authors: Gallavan R. H. , Shaw C. , Murphy R. F. , Buchanan K. D. , Joffe S. N. , Jacobson E. D.
Published: December 2017

The purpose of this study was to evaluate the role of neurotensin in the local regulation of the lipid-induced jejunal hyperemia. Total blood flow and the arteriovenous hormone concentration difference 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 produced a sustained increase (+25 +/- 3%) in jejunal blood flow, whereas neurotensin release reached a maximum (1.14 +/- 0.34 pmol X min-1 X 100 g-1) 2 min after initiation of the response and then returned to control. Venous neurotensin concentrations also reached a maximum (51 +/- 17 pmol/l) at 2 min. There were no significant changes in either blood flow or neurotensin release in response to the other test solutions. Intra-arterial infusion of neurotensin did not significantly decrease jejunal vascular resistance (-12 +/- 3%) until venous concentrations of 478 +/- 101 pmol/l were attained. It seems unlikely, then, that neurotensin plays any role in the regulation of the lipid-induced jejunal hyperemia
Role of glucagon in splanchnic hyperemia of chronic portal hypertension
Authors: Benoit J. N. , Zimmerman B. , Premen A. J. , Go V. L. , Granger D. N.
Published: December 2017

The role of glucagon as a blood-borne mediator of the hyperdynamic circulation associated with chronic portal venous hypertension was assessed in the rat portal vein stenosis model. Selective removal of pancreatic glucagon from the circulation was achieved by intravenous infusion of a highly specific glucagon antiserum. Blood flow to splanchnic organs, kidneys, and testicles was measured with radioactive microspheres, and the reference-sample method. Glucagon antiserum had no effect on blood flow in the gastrointestinal tract of sham-operated (control) rats. However, the antiserum produced a significant reduction in hepatic arterial blood flow in the control rats, suggesting that glucagon contributes significantly to the basal tone of hepatic arterioles. In portal hypertensive rats glucagon antiserum significantly reduced blood flow to the stomach (22%), duodenum (25%), jejunum (24%), ileum (26%), cecum (27%), and colon (26%). Portal venous blood flow was reduced by approximately 30%. The results of this study support the hypothesis that glucagon mediates a portion of the splanchnic hyperemia associated with chronic portal hypertension.
Effects of taurine-conjugated bile salts on ionic transport of the rabbit esophageal mucosa
Authors: Goldstein J. L. , Schmidt L. N. , Al-Bazzaz F. J. , Layden T. J.
Published: December 2017

Bile salts have been implicated as a cause of esophageal injury. We examined in vitro the changes in ionic transport of the rabbit esophagus resulting from taurine-conjugated bile salts at neutral pH to define and characterize their actions independent of hydrogen ion. In an Ussing chamber changes in potential difference (PD, mV), short-circuit current (SCC, microA X cm-2) and resistance (R, omega X cm2) resulting from taurocholate (TC), taurodeoxycholate (TDC) and taurochenodeoxycholate (TCDC) were studied. Transport properties were unaffected by TC at 5 and 10 mM. With TDC (5 mM) there was an initial rise in SCC and PD. After 60 min PD and R declined in association with an increase in paracellular permeability as measured by [14C]sucrose flux. TCDC (5.0 and 7.5 mM) caused a sustained rise in PD and SCC with a greater rise seen at 7.5 mM. The rise in SCC after TCDC was secondary to an increase in net sodium absorption as basal net sodium absorption increased threefold from 0.15 +/- 0.03 to 0.44 +/- 0.10 mu eq X cm-2 X h-1. Increased net sodium absorption accounted for 73% of the TCDC-induced rise in SCC. Amiloride (10(-4) M) added to the mucosal solution significantly inhibited this bile salt-induced rise in SCC. We conclude that bile salts alter ionic transport in the esophageal mucosa independent of hydrogen ion. These changes are characterized by an early selective increase in apical membrane cation conductance and with longer exposure, particularly in the presence of more hydrophobic bile salts, there is a marked increase in paracellular conductance.
Vagally mediated gastric relaxation induced by intestinal nutrients in the dog
Authors: Azpiroz F. , Malagelada J. R.
Published: December 2017

Using a gastric barostat to measure gastric tone, we previously demonstrated that nutrient perfusion into the intestine induces gastric relaxation. To investigate the pathway of this enterogastric reflex we surgically isolated the vagi either in a cervical skin tunnel (3 dogs) or within an implanted supradiaphragmatic cooling jacket (3 dogs). In the conscious fasted dogs, cervical or supradiaphragmatic vagal blockade by cooling (5 degrees C X 10 min) induced a reversible gastric relaxation. Bethanechol (0.2 mg X kg-1 X h-1 iv) alone or in combination with adrenergic blockers (phentolamine 1.5 mg X kg-1 X h-1 + propranolol 0.3 mg X kg-1 X h-1) suppressed the cooling-induced relaxation but did not abolish gastric relaxation induced by intestinal nutrient perfusion (Osmolite, 3.1 ml/min). At this point, vagal cooling, either cervical or supradiaphragmatic, reversibly blocked the nutrient-induced gastric relaxation: gastric tone significantly increased driven by the cholinergic background and reverted after vagal rewarming to the previous relaxed state. We conclude that intestinal nutrients induce gastric relaxation by a nonadrenergic noncholinergic mechanism. This reflex is mediated by fibers contained in the vagus nerves at both cervical and supradiaphragmatic levels.
Lower esophageal sphincter relaxation is associated with increased cyclic nucleotide content
Authors: Torphy T. J. , Fine C. F. , Burman M. , Barnette M. S. , Ormsbee H. S.
Published: December 2017

Experiments were conducted to determine whether relaxation of the opossum isolated lower esophageal sphincter (LES), induced by electrical field stimulation (EFS) or various pharmacological agents, is associated with changes in cyclic nucleotide content. EFS relaxed the LES in a frequency-dependent manner with 0.7 Hz producing half-maximal relaxation. Control tissues and tissues stimulated at various frequencies were clamp-frozen and assayed for cyclic nucleotide content. EFS had no effect on adenosine 3',5'-cyclic monophosphate (cAMP) content but increased guanosine 3',5'-cyclic monophosphate (cGMP) content in a frequency-dependent manner. Tetrodotoxin eliminated both the relaxation and cGMP accumulation in response to EFS. Vasoactive intestinal polypeptide (VIP) relaxed the LES with an EC50 of 0.1 microM. In contrast to the results with EFS, VIP enhanced cAMP content but had no effect on cGMP content. Relaxation of the LES produced by sodium nitroprusside or atriopeptin II was accompanied by an increase in cGMP accumulation, whereas isoproterenol- and dopamine-induced relaxation was accompanied by an increase in cAMP content. The data indicate that, depending on the stimulus, increases in either cAMP or cGMP content can accompany LES relaxation. These results are consistent with the proposed role of cyclic nucleotides as second messengers mediating LES relaxation.
Blood flow responses to small bowel resection
Authors: Ulrich-Baker M. G. , Hollwarth M. E. , Kvietys P. R. , Granger D. N.
Published: December 2017

The objective of this study was to determine whether the gastrointestinal blood flow response to small bowel resection is related to the compensatory hyperplasia resulting from resection. In one group of rats, a laparotomy was performed and 80% of the small bowel resected, reanastomosing proximal jejunum with distal ileum. In the second group (controls), a transection followed by reanastomosis was performed either in the jejunum or ileum. One, two, three, or five days later, the animals were anesthetized, and blood flows to the stomach, jejunum, ileum, cecum, colon, and pancreas were measured using the radioactive microsphere technique. Samples of these tissues were obtained for determination of thymidine incorporation and DNA content. Growth, as evidenced by increases in tissue weight, DNA content, and rate of DNA synthesis, occurred in all tissues. Blood flow was elevated in the pancreas and in bowel segments (ileum and cecum) distal to the site of resection. Gastric, jejunal and colonic blood flows were not affected by bowel resection, in spite of similar trophic changes. Paired-value analyses did not reveal any correlation between blood flow and rate of DNA synthesis. The results of these studies suggest that humoral, rather than metabolic, factors are responsible for the gastrointestinal and pancreatic hyperemia that occurs after small bowel resection.
Transport of acidic amino acids by human jejunal brush-border membrane vesicles
Authors: Rajendran V. M. , Harig J. M. , Adams M. B. , Ramaswamy K.
Published: December 2017

This study characterizes the transport of radiolabeled acidic amino acids into brush-border membrane vesicles prepared from human jejunum. The uptakes of L-glutamic, L-aspartic, and D-aspartic acids were stimulated by a Na+ gradient (extravesicular greater than intravesicular). Concentrative uptake (resulting in an "overshoot" phenomenon) of these dicarboxylic amino acids occurred when there was an outward K+ gradient (intravesicular greater than extravesicular). In addition, increasing K+ gradients (0-100 mM) resulted in enhanced uptake of L-glutamic acid. This K+ requirement is somewhat specific as Rb+ and Cs+ could enhance uptake to a limited extent, whereas Li+ and choline+ showed no enhancement. The presence of a K+ gradient did not affect the affinity of the carrier system for L-glutamic acid but it did increase the Vmax. The presence of extravesicular anions having differing membrane permeabilities did not alter L-glutamic acid uptake indicating an absence of an effect of membrane potential on the transport process. Finally, the human transport system for L-glutamic acid appears to be specific for acidic amino acids as demonstrated by inhibition studies. Our studies demonstrate a transport system in human jejunum specific for acidic amino acids that is energized by an inward Na+ gradient and an outward K+ gradient.
Regulation of Na-Cl absorption in rabbit proximal colon in vitro
Authors: Sellin J. H. , De Soignie R.
Published: December 2017

Ion transport in rabbit proximal colon (PC) in vitro is dominated by a Na-Cl cotransport system stimulated by epinephrine. To further characterize the regulation of Na-Cl transport, we tested the effects of specific adrenergic agonists on ion fluxes under short-circuit conditions. Additionally, we tested the effects of the transport inhibitors bumetanide, furosemide, and 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS). Basal Na and Cl absorption were essentially nil [Na net flux (JNanet) = 0.3 +/- 0.4, and Cl net flux (JClnet) = -0.5 +/- 0.5 mu eq X cm-2 X h-1, means +/- SE]. The alpha 2-agonist clonidine significantly increased net Na and Cl absorption (delta JNanet = 3.0 +/- 0.6 mu eq X cm-2 X h-1, delta JClnet = 2.0 +/- 0.4 mu eq X cm-2 X h-1) with a minimal change in short-circuit current (delta Isc = 0.1 +/- 0.1 mu eq X cm-2 X h-1). The alpha 1-agonist phenylephrine and the beta-agonist isoproterenol did not alter ion transport. The alpha 2-blocker yohimbine (YOH) had a complex, concentration-dependent effect. At low concentrations (10(-6)-10(-8) M) YOH effectively inhibited epinephrine-stimulated cotransport. Compared with 10(-8)M YOH, 10(-6) YOH blocked 90% of the epinephrine-induced increases in Na and Cl absorption.(ABSTRACT TRUNCATED AT 250 WORDS)
A carrier-mediated system for transport of biotin in rat intestine in vitro
Authors: Said H. M. , Redha R.
Published: December 2017

Transport of biotin was examined in rat intestine using the everted sac technique. Transport of 0.1 microM biotin was linear with time for at least 30 min of incubation and occurred at a rate of 3.7 pmol X g initial tissue wet wt-1 X min-1. Transport of biotin was higher in the jejunum than the ileum and was minimum in the colon (85 +/- 6, 36 +/- 6, and 2.8 +/- 0.6 pmol X g initial tissue wet wt-1 X 25 min-1, respectively). In the jejunum, transport of biotin was saturable at low concentrations (Kt = 3.73, microM, Vmax = 3.11 nmol X g initial tissue wet wt-1 X 25 min-1) but linear at higher concentrations (greater than 10 microM). The transport of low concentrations of biotin was inhibited by structural analogues (desthiobiotin, biotin methyl ester, diaminobiotin, and biocytin), Na+ dependent, energy dependent, temperature dependent, and proceeded against a concentration gradient in the serosal compartment. No metabolic alteration occurs to the biotin molecule during transport. This study demonstrates that biotin transport in rat intestine occurs by a carrier-mediated process at low concentrations and by simple diffusion at high concentrations. Furthermore, the carrier-mediated process is Na+, energy, and temperature dependent.
Pyloric ceca of fish: a "new" absorptive organ
Authors: Buddington R. K. , Diamond J. M.
Published: December 2017

The functions of the blind appendages attached to the proximal intestine of many fish, the pyloric ceca, have been disputed. Hence we recorded morphological parameters and nutrient uptake rates in the ceca and intestine of four fish species (rainbow trout, cod, largemouth bass, and striped bass) with various degrees of cecal development (the ceca contribute 70, 69, 42, and 16% of the total postgastric surface area, respectively). Proline and glucose uptake, measured in vitro, is similar in the ceca and proximal intestine. For these two solutes in these four species, and for 10 other solutes (9 amino acids and 1 dipeptide) in trout, the ceca contribute about the same percentage to uptake as to total gut area. Trout ceca and intestine have similar membrane-bound disaccharidase activity. Separate experiments with trout fed either graded glass beads or a radiopaque marker and then X-rayed show that the ceca fill and empty with particles less than 150 microns and over the same time course as the proximal intestine. Thus ceca are an adaptation for increasing intestinal surface area without increasing the length or thickness of the intestine itself. Fish ceca are entirely different from the distally located ceca of birds and mammals, which have fermentation functions.
Carbachol regulates cholecystokinin receptor on pancreatic acinar cells
Authors: Honda T. , Adachi H. , Noguchi M. , Sato S. , Onishi S. , Aoki E. , Torizuka K.
Published: December 2017

We have examined the effect of carbamylcholine on the binding of cholecystokinin (CCK) to dispersed acini from rat pancreas. The CCK receptor on pancreatic acini possesses two classes of binding sites. Simultaneous addition of carbamylcholine inhibited binding of CCK to acini due to an apparent loss of high affinity CCK binding sites. Atropine prevented the inhibitory effect of carbamylcholine, whereas calcium ionophore A23187 did not alter binding of CCK. 12-O-tetradecanoylphorbol-13-acetate (TPA) inhibited binding of CCK in the same manner as carbamylcholine. Inhibition by carbamylcholine was reversible and the recovery was time dependent. By contrast, inhibition of binding of CCK by TPA did not reverse after a 60-min incubation without the agent. These findings, at least in part, account for the inhibition of the CCK-induced stimulation of amylase secretion by carbamylcholine. The action of TPA on binding of CCK suggests the possible involvement of the activation of protein kinase C in the inhibition of binding.
A high linoleic acid diet diminishes enhanced intestinal uptake of sugars in diabetic rats
Authors: Thomson A. B. , Keelan M. , Clandinin M. T. , Walker K.
Published: December 2017

Intestinal absorption is altered in rats by diabetes and by dietary manipulation. For 5 wk rats were fed chow (C) or semisynthetic diets containing isocaloric amounts of a high content of either polyunsaturated (P) or saturated (S) fatty acids; then half were rendered hyperglycemic with streptozotocin while the remaining half served as nondiabetic controls. Studies were performed after a total of 8 wk on C, P, or S. Jejunal villous surface area was greater in diabetic rats than in control rats fed C or S, whereas the jejunal mucosal surface area was significantly greater in diabetic animals than in control animals only when they were fed S. Ileal mucosal surface area was similar in diabetic and in control rats fed C, S, or P; although ileal villous surface area was greater in diabetic than in control rats only when they were fed C. The jejunal and ileal uptake of varying concentrations of glucose and galactose was higher in diabetic rats than controls fed C or S. In contrast, the enhanced uptake of these sugars was reduced or normalized in diabetic rats fed P. The jejunal brush-border membrane (BBM) content of phospholipids was higher in diabetic than in control rats fed chow, but there was no difference in diabetic vs. control animals fed P or S in BBM total free fatty acids, phospholipids, or cholesterol. Thus feeding a high linoleic acid diet diminishes the enhanced intestinal uptake of glucose and galactose in diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)