bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of selective proximal vagotomy without and with pyloroplasty on gastroduodenal motility
Authors: Holle G. E. , Reiser S. B. , Frey K. W.
Published: December 2017

The effect of selective proximal vagotomy (SPV) was examined in six dogs on the gastric emptying of solid food and the motility of the antrum and duodenum (basic rhythm, motility index, and contractile activity percentage). Emptying and motility were also examined in three dogs after additional submucosal pyloroplasty (SMP). Electrical and motor activities were tested in fasted and fed states. The meal consisted of 300 g of standard protein-mixed meal. Determination of gastric emptying by X ray were conducted with the same meal mixed with barium sulfate. All animals showed delayed emptying of solid food after SPV. Antral motility increased nonsignificantly in the digestive state, whereas duodenal motility decreased, resulting in an increased antroduodenal motor gradient. In the interdigestive state the motility of the antrum decreased significantly. Additional SMP normalized the emptying delay, but decreased digestive and interdigestive motility below the normal values. In conclusion, the emptying delay after SPV is caused at least in part by the altered functional condition of the immediate pyloric region.
Cytoprotective effect of sulfate ions in acid-exposed rabbit esophagus
Authors: Tobey N. A. , Orlando R. C. , Schreiner V. J. , Powell D. W.
Published: December 2017

Sodium sulfate significantly inhibited the decline in epithelial electrical resistance (R) produced by mucosal acidification (pH 1.4) of rabbit esophagus mounted in the Ussing chamber. This protective effect was not due to the cation, to sodium loading, hyperosmolality, or pH change of the mucosal solution. Protection was specific for sulfate ions (SO2–4), since other divalent (HPO2-4) or impermeant anions (gluconate-) failed to prevent the acid-induced decline in R. In vivo studies in HCl-perfused rabbit esophagi confirmed protection by SO2–4. Tissues exposed to SO2–4 and HCl had higher R, lower permeability to H+ and mannitol, and less morphologic damage than controls exposed to HCl. These results suggest that SO2–4 have a unique protective action against acid injury to esophageal epithelia, and this action appears to explain the cytoprotective properties of sucralfate, a clinically effective agent for treating acid-peptic disease in humans.
Effect of enkephalins on colonic mechanoreceptor synaptic input to inferior mesenteric ganglion
Authors: Shu H. D. , Love J. A. , Szurszewski J. H.
Published: December 2017

The effects of leucine-enkephalin (Leu-Enk) on colonic mechanoreceptor input to the inferior mesenteric ganglion (IMG) and on colonic intraluminal pressure of the guinea pig were studied in vitro. Superfusion of the IMG with Leu-Enk decreased colonic, afferent mechanoreceptor synaptic input. In neurons in which mechanoreceptor input caused postsynaptic spikes, Leu-Enk decreased synaptic input and increased the basal intraluminal pressure of the colon. When mechanoreceptor input consisted of singly occurring excitatory postsynaptic potentials (EPSPs), Leu-Enk decreased the frequency of EPSPs but did not cause a change in colonic pressure. The inhibitory effects of Leu-Enk on synaptic transmission were antagonized by naloxone. In the isolated IMG, Leu-Enk converted synchronous action potentials in response to electrical stimulation of intermesenteric nerves to subthreshold EPSPs without a change in the resting membrane potential or input resistance. Action potentials elicited by depolarizing current pulses or by exogenous acetylcholine were unaltered by Leu-Enk. These data suggest that Leu-Enk increased colonic intraluminal pressure by acting on the presynaptic terminals of colonic mechanoreceptive neurons to reduce synaptic input to and output from the inhibitory neurons of the IMG.
Role of GIP and insulin in glucose-induced changes in intestinal motility patterns
Authors: Thor P. , Laskiewicz J. , Konturek J. W. , Konturek S. J. , Creutzfeldt W.
Published: December 2017

This study was designed to correlate the intestinal motility patterns with duodenal glucose loads and the increments in plasma gastric inhibitory peptide (GIP) and insulin levels after these loads or after the administration of exogenous hormones in conscious dogs. Isotonic glucose instilled intraduodenally at lower loads (5.2-42.4 mmol/h) only caused a moderate increase in spike activity, but at higher loads (84.8 mmol/h) it disrupted migrating myoelectric complexes (MMC), being accompanied by marked increases in plasma GIP and insulin levels. Duodenal loads of isotonic mannitol resulted in similar motility changes but without alteration in plasma GIP or insulin. Hypertonic glucose (20%) in the duodenum also caused an increase in spike activity, and at higher loads (72 mmol/h or higher) it disrupted MMCs and resulted in significant increments in plasma GIP and insulin levels. Physiological doses of exogenous GIP (25-400 pmol X kg-1 X h-1) or insulin (12-24 mU X kg-1 X h-1) did not affect the motility pattern, but at higher doses, raising plasma hormone over the levels occurring after a mixed meal, GIP (400 pmol X kg-1 X h-1) increased significantly the MMC interval, whereas insulin (48-96 pmol X kg-1 X h-1) induced a fed-like motility pattern. Intravenous 20% glucose (72 mmol/h) caused a marked rise in plasma insulin (but not GIP) levels but failed to affect the intestinal motility as did 20% mannitol infused intravenously in the same dose.(ABSTRACT TRUNCATED AT 250 WORDS)
Role of sulfate ester in influencing biologic activity of cholecystokinin-related peptides
Authors: Vinayek R. , Jensen R. T. , Gardner J. D.
Published: December 2017

In dispersed acini from guinea pig, mouse, or rat pancreas cholecystokinin-(27-33) is a full agonist, and removing the sulfate ester from the tyrosine residue in position 27 caused a 100- to 300-fold decrease in potency with no change in efficacy. In dispersed acini from mouse or rat pancreas, cholecystokinin-(27-32)-NH2 is a partial agonist, and removing the sulfate ester from the tyrosine in position 27 abolished the efficacy. The desulfated peptide was able, however, to interact with CCK receptors with a potency that was threefold less than that of cholecystokinin-(27-32)-NH2 and therefore functioned as a cholecystokinin receptor antagonist. In dispersed acini from guinea pig pancreas cholecystokinin-(27-32)-NH2 is a cholecystokinin receptor antagonist. Removing the sulfate ester from the tyrosine residue in position 27 of cholecystokinin(27-32)-NH2 caused a fourfold decrease in potency but did not abolish the ability of the peptide to interact with cholecystokinin receptors; therefore, desulfated cholecystokinin-(27-32)-NH2 functioned as a cholecystokinin receptor antagonist.
Effect of epidermal growth factor on polyamine-synthesizing enzymes in rat enterocytes
Authors: Fitzpatrick L. R. , Wang P. , Johnson L. R.
Published: December 2017

A number of peptides having trophic activity on gastrointestinal mucosa and growth factors are known to induce small intestinal ornithine decarboxylase (ODC) activity. The effect of peptides on ODC and S-adenosylmethionine (SAMDC) activities (key enzymes in polyamine biosynthesis) in isolated enterocytes is unknown. Male Sprague-Dawley rats were fasted for 72 h and injected intraperitoneally with epidermal growth factor (EGF), pentagastrin, or glucagon, or intragastrically with EGF. A similar volume of water served as a control. Villus tip, midvillus, and crypt cell fractions were collected and identified. ODC and SAMDC activities were determined in these cells 4 h after peptide injection. EGF given intraperitoneally, but not intragastrically, stimulated ODC activity along the cryptvillus column. Pentagastrin and glucagon did not induce polyamine biosynthetic enzyme activity. ODC and SAMDC activities in intestinal mucosal scrapings from fasted animals also were increased 2-4 h after intraperitoneal EGF treatment. It is possible that EGF binding at the serosal surface of the crypt enterocyte and subsequent ODC induction is important in initiating the cellular proliferation that is known to occur after treatment with this peptide.
Folate transport by human intestinal brush-border membrane vesicles
Authors: Said H. M. , Ghishan F. K. , Redha R.
Published: December 2017

Transport of folic acid (Pte-Glu) across the brush-border membrane of human intestine was studied using brush-border membrane vesicle (BBMV) technique. The transport of Pte-Glu was higher in BBMV prepared from the jejunum than those prepared from the ileum (0.70 +/- 0.05 and 0.14 +/- 0.02 pmol X mg protein-1 X 10 s-1, respectively). The transport of Pte-Glu appeared to be carrier mediated and was pH dependent and increased with decreasing incubation buffer pH; saturable (Kt = 1.69 microM, Vmax = 4.72 pmol X mg protein-1 X 10 s-1); inhibited in a competitive manner by the structural analogues 5-methyltetrahydrofolate, methotrexate, and 5-formyltetrahydrofolate (Ki = 2.2, 1.4 and 1.4 microM, respectively); not affected by inducing a relatively positive or negative intravesicular compartment; independent of Na+ gradient; and inhibited by 4,4'-diisothiocyanatostlibene-2,2'-disulfonic acid (DIDS), an anion exchange inhibitor. The increase in Pte-Glu transport on decreasing incubation buffer pH appeared to be in part mediated through a direct effect of acidic pH on the transport carrier and in part through the pH gradient imposed by activating Pte-Glu-:OH- exchange and/or Pte-Glu-:H+ co-transport mechanisms. The important role of an acidic extravesicular environment in Pte-Glu transport is consistent with a role for the intestinal surface acid microclimate in folate transport. These results demonstrate that Pte-Glu transport in human BBMV occurs by a carrier-mediated system that is similar to that described for rat and rabbit intestinal BBMV.
Hyperglucagonemia and hyperkinetic circulation after portocaval shunt in the rat
Authors: Kravetz D. , Arderiu M. , Bosch J. , Fuster J. , Visa J. , Casamitjana R. , Rodes J.
Published: December 2017

The study was aimed at investigating whether increased portal venous inflow (PVI) after portocaval shunt (PCS) in the rat is the result of selective splanchnic vasodilatation or whether it is part of a generalized circulatory disturbance. Rats with PCS (n = 9) and sham-operated controls (n = 8) were studied 2 wk after surgery by measuring cardiac output (CO), PVI, and hepatic artery flow (HAF) with radioactive microspheres. Plasma glucagon (GL) was measured by radioimmunoassay. PCS rats had increased CO (46.2 +/- 2.8 vs. 28.2 +/- 1.7 ml X min-1 X 100 g-1, P less than 0.001) and reduced arterial pressure and total peripheral resistance. PVI was markedly increased (7.7 +/- 0.7 vs. 4.3 +/- 0.2 ml X min-1 X 100 g-1, P less than 0.001), but this appeared to be part of a generalized circulatory disturbance, since when PVI is expressed as percent of CO no difference is observed between PCS and sham-operated rats (17.0 +/- 1.5 vs. 15.8 +/- 1.3%, NS), indicating the absence of a preferential splanchnic vasodilatation. GL increased after PCS (548 +/- 130 vs. 156 +/- 23 pg/ml, P less than 0.005), and significant correlations were observed between GL and CO (r = 0.787, P less than 0.001) and between GL and PVI (r = 0.806, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Characteristics of glycyl-L-proline transport in intestinal brush-border membrane vesicles
Authors: Rajendran V. M. , Harig J. M. , Ramaswamy K.
Published: December 2017

A proton-peptide symport mechanism has been postulated for transport of dipeptides in rabbit intestinal and renal brush-border membrane vesicles (BBMV). We have investigated the effects of a transmembrane potential (in mouse) and an inwardly directed proton gradient (in mouse, rabbit, and human) on the transport of glycyl-L-proline in intestinal BBMV. Membrane potential alterations, induced by permeant anions or generated by a K+-diffusion potential in the presence of valinomycin, did not accelerate the uptake of glycyl-L-proline. In contrast, in parallel experiments the uptake of D-glucose, whose cotransport system is electrogenic, was markedly increased by an interior negative membrane potential. Thus the transport of glycyl-L-proline in mouse intestinal BBMV is not electrogenic. Further studies on the effect of a proton gradient (extravesicular pH 5.5; intravesicular pH 7.5) on transport of glycyl-L-proline revealed an absence of stimulation of glycyl-L-proline transport and lower uptake rates in the presence of a proton gradient. The simultaneous presence of an interior negative membrane potential and an inwardly directed proton gradient did not accelerate the transport of glycyl-L-proline. These results demonstrate that the transport of glycyl-L-proline in mouse intestinal BBMV is neither electrogenic nor energized by an inwardly directed proton gradient. Likewise, pH gradients do not stimulate glycyl-L-proline uptake in either rabbit or human BBMV.
Biological activity of progastrin posttranslational processing intermediates
Authors: Matsumoto M. , Park J. , Sugano K. , Yamada T.
Published: December 2017

We recently identified carboxyl-terminally extended progastrin posttranslational processing intermediates in G cells of the gastric antrum and demonstrated that they are cosecreted with gastrin. To determine the physiological significance of these intermediates, we examined the biological activity of two synthetic gastrin precursor analogues that correspond to hexagastrin with carboxyl-terminal extensions, Tyr-Gly-Trp-Met-Asp-Phe-Gly (GL-7) and Tyr-Gly-Trp-Met-Asp-Phe-Gly-Arg-Arg (GL-9) on gastric parietal and D cells isolated from canine fundic mucosa. Both analogues were as efficacious as gastrin heptadecapeptide in displacing 125I-[Leu15]gastrin from binding sites on the two cell types and in stimulating [14C]aminopyrine uptake by parietal cells and somatostatin release from D cells. However, both analogues were 10(4)- to 10(5)-fold less potent than gastrin heptadecapeptide in these activities. Our results indicate that progastrin processing intermediates do not have physiologically relevant actions under normal circumstances and support the notion that carboxyl-terminally amidated peptides such as gastrin require the amide moiety for biological activity.
Sensitivities of human jejunum, ileum, proximal colon, and gallbladder to cholecystokinin octapeptide
Authors: Kellow J. E. , Miller L. J. , Phillips S. F. , Haddad A. C. , Zinsmeister A. R. , Charboneau J. W.
Published: December 2017

We compared in humans simultaneous motor responses of the jejunum, ileum, proximal colon, and gallbladder (GB) to intravenous cholecystokinin octapeptide (CCK-OP). To gauge the physiological relevance of the doses of CCK-OP, intestinal motility and GB contraction were also quantified after a fatty meal. Eight healthy volunteers participated in both experiments. Six graded, 30-min intravenous infusions had a mean range of 2.2 to 73.2 pmol X kg-1 X h-1 of CCK-OP; these spanned from subphysiological (negligible contraction of GB) to pharmacological (producing intestinal symptoms and a 70–99% contraction of GB) levels. CCK-OP inhibited interdigestive cycles of motility, though in some persons fasting patterns persisted with doses of CCK-OP, which produced up to 50% reduction in GB volume. Motility indices of the ileum and proximal colon responded to CCK-OP by decreasing initially but then increasing with larger doses; motility of the jejunum increased gradually at all doses. Judged by the gallbladder's response to food (reduction in volume down from 74 to 29% of original volume), the physiological range of infused CCK-OP was approximately 5–16 pmol X kg-1 X h-1. Within this range of doses of CCK-OP, motility of the jejunum increased, whereas motility of the proximal colon was reduced. These data are consistent with CCK being a “physiological” mediator of intestinal motility in humans; responses of the intestine to the peptide appear to vary regionally.
Short-term cholinergic desensitization of rat pancreatic secretory response
Authors: Asselin J. , Larose L. , Morisset J.
Published: December 2017

Dispersed pancreatic acini were first exposed to carbamylcholine (10(-7)-10(-4) M) for 60 min, washed, and reexposed to this same agonist (10(-8)-10(-3) M) for 15 min. During this second incubation, the functional secretory capacity of these acini was evaluated by measuring amylase release. Acini preexposed to concentrations of carbamylcholine of 10(-6) M or greater showed shifts to the right in the subsequent carbamylcholine dose-response curves of amylase release. A 3-h recovery period (without carbamylcholine) did not restore the altered carbamylcholine dose-response curve. Ca2+ concentrations of 10(-7) M or 2.5 X 10(-3) M instead of 0.5 X 10(-3) M during the 60-min preincubation did not affect the desensitization process. With use of N-[3H]methylscopolamine to evaluate muscarinic receptors, the only changes observed after desensitization were a significant decrease in the high-affinity and an equivalent increase in that of the low-affinity receptors. After cholinergic exposure amylase release stimulated by caerulein was only slightly modified, whereas amylase release in response to a phorbol ester 12-O-tetradecanoylphorbol-13-acetate and to the ionophore A23187 was not altered. These data indicate that short-term desensitization with a cholinergic agent is relatively specific to muscarinic agonists, causes changes in the muscarinic receptor high- and low-affinity concentration but does not alter intracellular steps after calcium mobilization or protein kinase C activation known to be involved in the secretion process.
Bombesin stimulation of gastrin release from canine gastrin cells in primary culture
Authors: Giraud A. S. , Soll A. H. , Cuttitta F. , Walsh J. H.
Published: December 2017

A method is described for the isolation and short-term culture of canine antral gastrin (G) cells. Tissue was dispersed by enzymes and G cells enriched by elutriation and cultured for 40 h. These cultures contained 12% G cells and less than 2% somatostatin- or serotonin-containing cells. Bombesin (0.001–100 pM) potently stimulated gastrin release from cell cultures in a linear fashion over 2 h. The bombesin-specific monoclonal antibody 2A11 dose-dependently blocked bombesin stimulation. Somatostatin (0.001–1,000 nM) inhibited bombesin-stimulated gastrin release. Antibody to somatostatin (Mab S8) prevented the inhibition by exogenous somatostatin but did not alter bombesin-stimulated or basal gastrin release. The substance P (SP) analogue spantide (1 nM-1 microM) did not inhibit bombesin-stimulated gastrin release. Postreceptor activation of adenylate cyclase by forskolin and of protein kinase C by the phorbol ester, beta-TPA, caused gastrin release. The calcium ionophore A23187 also released gastrin in a dose-dependent fashion. This methodology allows enrichment and short-term culture of antral G cells; these cells have stimulatory bombesin and inhibitory somatostatin receptors, suggesting that these peptides have a direct action on antral G cells. Furthermore, G cells are activated by cAMP and calcium/phosphatidylinositol-dependent mechanisms.
Phorbol esters and A23187 regulate Na+-K+-pump activity in pancreatic acinar cells
Authors: Hootman S. R. , Brown M. E. , Williams J. A.
Published: December 2017

To clarify the subcellular mechanisms that mediate stimulation of Na+-K+-pump activity in pancreatic acinar cells by cholinergic agonists, we examined the effects of the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA) and the Ca2+ ionophore A23187 on [3H]ouabain binding to dispersed guinea pig pancreatic acinar cells under conditions in which binding reflects the average rate of pump cycling. The phorbol ester more than doubled Na+-K+-pump activity as did the diacylglycerol analogue, 1-oleoyl-2-acetolyl-sn-3-glycerol. A23187 increased pump activity by a maximum of 31% at 0.3 microM but was progressively inhibitory at higher concentrations. The stimulatory effects of TPA and A23187 were additive, although either secretagogue elicited a less than additive response when added together with a maximally effective concentration of the cholinergic agonist, carbachol. Removal of extracellular Ca2+ had little effect on the pump response to TPA and did not reduce the maximal effect of A23187 but abolished the inhibitory effect seen at high ionophore concentrations in Ca2+-containing medium. These results indicate that both Ca2+ and protein kinase c are involved in regulating Na+-K+-pump activity in the pancreatic acinar cell.
Development of cholecystokinin binding sites in rat upper gastrointestinal tract
Authors: Robinson P. H. , Moran T. H. , Goldrich M. , McHugh P. R.
Published: December 2017

Autoradiography using 125I-labeled Bolton Hunter-CCK-33 was used to study the distribution of cholecystokinin binding sites at different stages of development in the rat upper gastrointestinal tract. Cholecystokinin (CCK) binding was present in the distal stomach, esophagus, and gastroduodenal junction in the rat fetus of gestational age of 17 days. In the 20-day fetus, specific binding was found in the gastric mucosa, antral circular muscle, and pyloric sphincter. Mucosal binding declined during postnatal development and had disappeared by day 15. Antral binding declined sharply between day 10 and day 15 and disappeared by day 50. Pyloric muscle binding was present in fetal stomach and persisted in the adult. Pancreatic CCK binding was not observed before day 10. These results suggest that CCK may have a role in the control of gastric emptying and ingestive behavior in the neonatal rat.
Processing of receptor-bound somatostatin: internalization and degradation by pancreatic acini
Authors: Viguerie N. , Esteve J. P. , Susini C. , Vaysse N. , Ribet A.
Published: December 2017

We have previously demonstrated the presence of specific binding sites for somatostatin on plasma membranes from pancreatic acinar cells. In the present study we attempted to characterize the fate of receptor-bound 125I-[Tyr11]somatostatin. Internalization of somatostatin was rapid (reaching a plateau at 20% of the cell-associated specific radioactivity) and temperature dependent. To follow the processing of bound somatostatin, acini were incubated with 125I-[Tyr11]somatostatin at 5 degrees C during 16 h then, after washing, incubated at 37 degrees C for 90 min in fresh medium. Surface-bound somatostatin decreased rapidly, whereas radioactivity increased in the cell interior and the incubation medium. Intracellular and membrane-bound radioactivity was mainly intact 125I-[Tyr11]somatostatin. Degradation occurred at the plasma membrane level and led to iodotyrosine production. After 15 min of incubation, 15% of the initially surface-bound 125I-[Tyr11]somatostatin was compartmentalized within the cell, mainly in the microsomal fraction. After 30 min, a significant increase in radioactivity appeared in the nuclear fraction. These results indicate that the major part of somatostatin cellular degradation takes place at the plasma membrane level. Within the cell, somatostatin is routed to the nucleus via particular fractions sedimenting with microsomal vesicles.
Dihydroxy bile salt-induced secretion of rubidium ion across the rabbit distal colon
Authors: Freel R. W.
Published: December 2017

Possible mechanisms of dihydroxy bile salt-induced K+ secretion by the mammalian colon were evaluated by studying the effects of taurochenodeoxycholate (TCDC) on 86Rb+ transport across the isolated, short-circuited rabbit distal colon. Simultaneous measurements of 86Rb+ and 42K+ unidirectional fluxes were highly correlated [r = 0.964 for serosal (s) to mucosal (m) and 0.765 for m to s], indicating that Rb+ is a suitable tracer for K+ transport across the colon. Furthermore, mucosal Ba2+ (4 mM) or serosal ouabain (0.1 mM) decreased serosal to mucosal rubidium flux (JRbs----m) (from 0.24 +/- 0.02 to 0.09 +/- 0.02, and 0.08 +/- 0.01 mu eq X h-1 X cm-2, respectively) without affecting JRbm----s. Dibutyryl cyclic adenosine monophosphate (dBcAMP, 0.5 mM serosal) specifically increased JRbs----m of controls (from 0.21 +/- 0.05 to 0.67 +/- 0.09 mu eq X h-1 X cm-2) through a barium- (4 mM, mucosal) sensitive pathway without affecting JRbs----m. Mucosal addition of 2 mM TCDC increased tissue conductance (GT), reduced short-circuit (Isc) slightly, and reversed JRbnet (from 0.13 +/- 0.05 to -0.29 +/- 0.08 mu eq X h-1 X cm-2) principally by increasing JRbs----m. The TCDC-induced increases in JRbs----m were reduced by 0.1 mM serosal ouabain (from 0.53 +/- 0.03 to 0.11 +/- 0.02 mu eq X h-1 X cm-2) or 4 mM mucosal Ba2+ (from 0.76 +/- 0.07 to 0.32 +/- 0.04 mu eq X h-1 X cm-2).(ABSTRACT TRUNCATED AT 250 WORDS)
Lymph protein concentration in initial and collecting lymphatics of the rat
Authors: Zawieja D. C. , Barber B. J.
Published: December 2017

Lymph samples were obtained from villus initial and mesenteric prenodal collecting lymphatics of the anesthetized rat using standard micropuncture techniques. The protein concentrations of the lymph samples were determined using a fluorometric microassay. These procedures were performed on preparations either superfused with a modified Krebs solution or covered with paraffin oil. The protein-concentrating ability of the intestinal lymphatics was evaluated to test the osmotic theory of lymph formation. The mean initial lymph protein concentration in superfused preparations was 2.08 g/dl (SE = 0.20). The lymph protein concentration in collecting vessels in superfused preparations was 2.20 g/dl (SE = 0.19). The protein concentration from initial lymphatics in oil-covered preparation was 2.48 g/dl (SE = 0.17). The lymph protein concentration in collecting vessels in oil-covered preparations was 2.32 g/dl (SE = 0.15). The difference between initial and collecting lymph protein concentration found was an order of magnitude lower than that predicted by the osmotic theory. These results cast serious doubts on the effectiveness of the osmotic mechanism of lymph formation as it is presently defined.
Cephalic phase of gastroduodenal alkaline secretion
Authors: Konturek S. J. , Thor P. , Bilski J. , Tasler J. , Cieszkowski M.
Published: December 2017

Alkaline secretion measured under basal conditions in the intact stomach of conscious dogs averaged 47 mumol/30 min and was about twice lower than that recorded in the proximal (approximately 7 cm long) portion of the duodenum. Vagal excitation elicited by sham feeding and insulin resulted in a marked stimulation of alkaline secretion both from the stomach and the duodenum. Atropine significantly reduced gastric and duodenal alkaline secretion under basal state. It abolished gastric and diminished duodenal alkaline response to sham feeding and insulin hypoglycemia, while propranolol was without significant influence. Indomethacin reduced by approximately 75% basal duodenal alkaline secretion but did not prevent the increment in alkaline response to vagal stimulation. We postulate the existence of the cephalic phase of gastroduodenal alkaline secretion, which seems to be cholinergically dependent in the stomach and partly of noncholinergic and nonadrenergic character but prostaglandin dependent in the duodenum.
Splanchnic hemodynamics in portal hypertensive dogs with portal fibrosis
Authors: Sugita S. , Ohnishi K. , Saito M. , Okuda K.
Published: December 2017

Splanchnic hemodynamics and portal systemic shunting were measured in eight dogs with experimentally induced portal fibrosis and splenomegaly and in six normal dogs by the radioactive microsphere technique. Portal fibrosis and splenomegaly were produced by repeated intraportal injections of a mixture of killed nonpathogenic Escherichia coli and dog anti-E. coli serum. All E. coli-treated dogs developed intrahepatic presinusoidal portal hypertension (portal vein pressure 15.8 +/- 5.4 vs. 7.5 +/- 0.9 mmHg in controls, P less than 0.005; intrahepatic pressure 6.8 +/- 2.1 vs. 6.2 +/- 1.4 mmHg in controls, NS) within 2.5 mo, but no portal systemic shunt was demonstrated at this time (2.1 +/- 1.5 vs. 0.7 +/- 0.4%, NS). Portal venous inflow, the total blood flow within the portal system, was increased in the treated dogs (27.6 +/- 6.6 vs. 18.2 +/- 2.5 ml X min-1 X kg body wt-1, P less than 0.005). Total splanchnic arterial vascular resistance was reduced in these dogs (26.0 +/- 10.4 vs. 40.9 +/- 4.6 dyn X s X cm-5 X 10(3), P less than 0.01) as a result of reduced arteriolar resistance in the spleen, jejunum and ileum, colon, and omentum, in all of which blood flow increased. In these animals both portal venous flow (27.0 +/- 6.5 vs. 18.1 +/- 2.5 ml X min-1 X kg body wt-1, P less than 0.005) and intrahepatic portal vascular resistance (1.9 +/- 0.7 vs. 0.7 +/- 0.3 dyn X s X cm-5 X 10(3), P less than 0.005) were increased.(ABSTRACT TRUNCATED AT 250 WORDS)
Absence of a cAMP-mediated antiabsorptive effect in an undifferentiated jejunal epithelium
Authors: MacLeod R. J. , Hamilton J. R.
Published: December 2017

In the relatively undifferentiated jejunal mucosa occurring in piglet viral enteritis, we measured the response of transepithelial Na+ and Cl- fluxes in vitro to raised intracellular adenosine 3',5'-cyclic monophosphate (cAMP) levels. At the acute 40-h stage of transmissible gastroenteritis (TGE), luminal membrane markers, sucrase and lactase, and a basolateral jejunal epithelial membrane marker Na+-K+-ATPase, were significantly decreased in activity, while a proliferative marker, thymidine kinase, was significantly enriched; these enzyme characteristics are typical of enterocytes isolated from crypts of other species. As expected, control piglet jejunum in short-circuited Ussing chambers after theophylline (10 mM) developed significant net secretory Na and Cl fluxes primarily due to significant antiabsorptive effects (delta JNa m----s = 3.48 +/- 0.52, delta JCl m----s = 2.59 +/- 0.28). Furosemide (10(-4) M), an inhibitor of electroneutral NaCl cotransport, produced antiabsorptive effects (delta JNa m----s = 2.53 +/- 0.31, delta JCl m----s = 2.58 +/- 0.28) in control jejunum that were not significantly different from those seen in response to theophylline. TGE jejunum, however, responded to theophylline not by an antiabsorptive effect but by significant electrogenic Cl- secretion (delta JCl s----m = 1.59 +/- 0.48); furosemide had no effect on ion fluxes in TGE tissue. Control and TGE jejunal mucosal homogenates did not differ in their basal or theophylline-stimulated levels of cAMP. We conclude that the relatively undifferentiated small intestine occurring in acute TGE does not generate either a cAMP-mediated antiabsorptive effect or a furosemide-mediated antiabsorptive effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Kinetic analysis of zinc uptake and serosal transfer by vascularly perfused rat intestine
Authors: Hoadley J. E. , Leinart A. S. , Cousins R. J.
Published: December 2017

Transport kinetics were examined for uptake of 65Zn from the lumen and for transport of mucosal 65Zn subsequent to uptake in the isolated, vascularly perfused intestines of rats fed either a zinc-deficient or zinc-adequate diet. Zinc depletion influenced the intestinal transport of zinc by stimulating a saturable uptake mechanism, reducing secretion of mucosal 65Zn into the lumen, and increasing the rate of 65Zn turnover in a rapidly absorbed mucosal zinc compartment. Uptake of 65Zn involved both saturable and nonsaturable processes. The saturable process was stimulated by zinc depletion with the apparent maximal transport rate for the saturable mechanism increasing from 60 to 180 nmol Zn X g-1 X 30 min-1. Most of the 65Zn taken up was not involved in the short-term secretion or absorption, and mucosal 65Zn retention was independent of dietary zinc status. Absorption of mucosal 65Zn was nonsaturable, involved a rapid exchanging zinc compartment, and was stimulated by zinc depletion. The half-life for 65Zn in this mucosal zinc compartment was approximately 24 min in the zinc-adequate group and 13 min in the zinc-depleted group.
Intestinal hyperemia in experimental diabetes mellitus
Authors: Korthuis R. J. , Benoit J. N. , Kvietys P. R. , Laughlin M. H. , Taylor A. E. , Granger D. N.
Published: December 2017

Intestinal blood flows were measured using the radioactive microsphere technique in anesthetized, fasted (18–24 h) rats 4 wk after administration of streptozotocin (65 mg/kg body wt) or its vehicle. Blood flow was increased along the length of the small bowel in diabetic rats relative to normal animals. In an attempt to define the mechanisms underlying the intestinal hyperemic response to diabetes, we employed an in situ, blood perfused, isolated rat jejunum-ileum preparation. Intestinal blood flow was increased by 37%, while intestinal vascular resistance was reduced by 39% in diabetic rats relative to control animals. Cross-perfusion of control intestinal preparations with arterial blood from diabetic rats produced a 30% increase in blood flow and a 24% reduction in vascular resistance. Increasing plasma osmolarity, plasma glucose concentration, or plasma glucagon concentration in control animals to levels measured in diabetic animals produced reductions in vascular resistance that were qualitatively similar to that seen in the diabetic intestine. Intestinal vascular sensitivity to norepinephrine was assessed by constructing dose-response curves in control anddiabetic animals. The mean ED50 values for norepinephrine were increased in diabetic rats relative to control animals. These results indicate that the intestinal hyperemic response in diabetes may be related to increased levels of circulating vasodilators, including hyperosmolarity and glucagon, and a reduced vascular sensitivity to norepinephrine.
Oxygen metabolite-induced cytotoxicity to cultured rat gastric mucosal cells
Authors: Hiraishi H. , Terano A. , Ota S. , Ivey K. J. , Sugimoto T.
Published: December 2017

Reactive oxygen metabolites have been reported to be responsible for the pathogenesis of ischemia-induced gastric mucosal lesions. We have investigated the possible protective effect of specific enzymes and oxygen radical scavenging agents on oxygen metabolite-induced injury to cultured gastric mucosal cells. Oxygen-reactive metabolites were generated by 1 mM xanthine and 10–100 mU/ml xanthine oxidase. Cytotoxicity was quantified by measuring 51Cr release from prelabeled cells. Xanthine oxidase caused a dose-dependent increase of 51Cr release in the presence of 1 mM xanthine. Catalase (an enzyme that reduces hydrogen peroxide) diminished xanthine-xanthine oxidase-induced 51Cr release in a dose-dependent manner. Superoxide dismutase (a scavenger of superoxide radical) failed to affect the amounts of 51Cr release induced by xanthine plus xanthine oxidase. Pretreatment with diethyl maleate, which depletes intracellular glutathione, potentiated oxygen radical-mediated 51Cr release dose dependently. The presence of ferrous ion or ethylenediaminetetraacetic acid-chelated iron, which promote the formation of hydroxyl radical, did not alter xanthine-xanthine oxidase-induced cellular injury. Furthermore, agents that inactivate hydroxyl radical also failed to protect the cells from oxygen metabolite-induced injury. We conclude that in vitro oxygen metabolites, extracellularly generated, have a direct toxic effect on gastric mucosal cells; hydrogen peroxide is a major mediator of oxygen metabolite-induced gastric cell injury; the oxygen-derived superoxide and hydroxyl radicals are less toxic to gastric mucosal cells than hydrogen peroxide; and intracellular glutathione, which detoxifies hydrogen peroxide, may be involved in antioxidant defense mechanisms.
A role for iron in oxidant-mediated ischemic injury to intestinal microvasculature
Authors: Hernandez L. A. , Grisham M. B. , Granger D. N.
Published: December 2017

Recent reports in the literature suggest that iron plays an important role in free radical-mediated injury in biological systems. To assess the role of iron-catalyzed oxidant production in ischemia-reperfusion injury, we examined the influence of deferoxamine (an iron chelator) and apotransferrin (iron transporting protein) on the increased intestinal vascular permeability produced by 1 h of ischemia and reperfusion. Both agents were administered intravascularly as a constant infusion, beginning 5 min before reperfusion. Capillary osmotic reflection coefficients were derived from the relationship between lymph-to-plasma protein concentration ratio and lymph flow in the feline small bowel. Vascular permeability in control intestinal preparations was 0.08 +/- 0.005, however it increased significantly to 0.40 +/- 0.03 in preparations subjected to 1 h of ischemia and 30 min of reperfusion. Vascular permeability in the deferoxamine-(0.15 +/- 0.009) and apotransferrin- (0.17 +/- 0.002) treated animals were significantly lower (P less than 0.01) than in the untreated group. Treatment with iron-loaded deferoxamine or transferrin did not offer any protection against ischemic injury. These findings support the hypothesis that iron plays an important role in the formation of hydroxyl radicals after reperfusion of the ischemic bowel.
Glucagon and insulin metabolism in a portal-hypertensive rat model
Authors: Sikuler E. , Polio J. , Groszmann R. J. , Hendler R.
Published: December 2017

The role that portosystemic shunting plays in inducing the alterations of glucagon and insulin metabolism, which are observed in chronic liver disease, was studied in a rat model of prehepatic portal hypertension induced by portal vein constriction. Net splanchnic output of the hormones into the portal circulation was calculated from the difference between portal and systemic concentrations multiplied by portal plasma flow. Metabolic clearance rate was calculated as the ratio between output and systemic concentration. Portal blood flow was measured by the radioactive microsphere technique. Glucagon output in the portal vein-ligated rats was higher than in the sham-operated controls (5.9 +/- 1.5 vs. 2.0 +/- 0.2 ng/min, P less than 0.05). The metabolic clearance rate of glucagon was not significantly different between the two groups. Insulin output was not significantly different between the two groups; however, the metabolic clearance rate of insulin in the portal vein-ligated rats was reduced in comparison with the sham-operated group (9.5 +/- 1.5 vs. 18.4 +/- 3.3 ml/min, P less than 0.05). Our results indicate that portosystemic shunting per se is sufficient to cause an increased splanchnic output of glucagon into the portal system and a decreased metabolic clearance of insulin.
Cardiac receptor modulation of blood flow and fluid transport in feline jejunum
Authors: Sjovall H. , Butcher P. , Martner J. , Sellden H.
Published: December 2017

The aim of the study is to determine the effects of selective cardiac receptor unloading on vascular resistance and net fluid transport in the small intestine. In anesthetized cats, cardiac receptors were unloaded by positive pressure ventilation (PPV). Arterial baroreceptor activity was artificially maintained constant. To test if the observed responses were due to a vagal reflex, experiments were performed both in animals with intact vagal nerves (n = 9) and after bilateral cervical vagotomy (n = 8). PPV-induced decreases in central blood volume (CBV) significantly increased intestinal vascular resistance (IVR) and net fluid absorption rate and decreased the transmural potential difference (PD). Cervical vagotomy per se also increased IVR and absorption rate and decreased PD. In vagotomized animals, decreases in CBV had no consistent effects on IVR, net fluid absorption rate, or PD. The results are compatible with cardiac receptor modulation of both blood flow and fluid absorption rate in the feline jejunum. Differences in the response patterns for the vascular and absorptive effects suggest that they may be mediated by separate efferent pathways.
Gastric injury induced by hemorrhage, local ischemia, and oxygen radical generation
Authors: Wadhwa S. S. , Perry M. A.
Published: December 2017

Gastric mucosal injury caused by local intra-arterial generation of oxygen-derived free radicals was compared with gastric injury caused by 30 min of hemorrhage-induced ischemia (systemic pressure of 30 mmHg) or local ischemia (celiac artery pressure of 30 mmHg). The index of injury was the loss of 51Cr-labeled red cells across the gastric mucosa. Generation of oxygen radicals in the celiac artery caused a rapid increase in mucosal blood loss during the period of radical generation (0.029 +/- 0.013 ml X min-1 X 100 g-1, mean +/- SE), and this loss was maintained after radical production ceased (0.041 +/- 0.018 ml X min-1 X 100 g-1). Local ischemia produced similar mucosal injury; however, this occurred after reperfusion of the stomach (0.038 +/- 0.006 ml X min-1 X 100 g-1) and not during the ischemic episode (0.001 +/- 0.0003 ml X min-1 X 100 g-1). Hemorrhage-induced ischemia produced a threefold greater mucosal blood loss (0.133 +/- 0.048 ml X min-1 X 100 g-1) than local ischemia. The results of this study indicate that oxygen radicals generated enzymatically in the blood supply to the stomach cause mucosal bleeding of similar magnitude to that observed after local ischemia and that gastric ischemia induced by systemic hypotension produces more severe gastric injury than the same level of local hypotension.
Activation of endogenous excitatory opiate pathways in canine small intestine by field stimulation and motilin
Authors: Fox J. E. , Daniel E. E.
Published: December 2017

Field stimulation of intrinsic nerves (40 V, 0.5 ms, 1-5 pps for 3-10 min) or intraarterial administration of motilin (10(-11)-10(-8 mol) caused contractions of the canine small intestine that were partially resistant to atropine and abolished by tetrodotoxin. Naloxone (10 micrograms ia or 200 micrograms/kg iv) in selective doses (10(-10)-10(-9) mol) that left responses to intra-arterial acetylcholine unaffected reduced responses to field stimulation or motilin in the ileum in the absence of atropine or residual responses in the presence of atropine. Results in the jejunum were similar except that selective doses of naloxone (10 micrograms ia or 200 micrograms/kg iv) increased the sensitivity to motilin in the absence of atropine. Higher doses of naloxone decreased these responses. In common with naloxone, tachyphylaxis to methionine-enkephalin (Met-Enk) reduced the responses to field stimulation or motilin before or after atropine but did not affect the responses to acetylcholine before or the responses to field stimulation of muscle after atropine. These findings are consistent with the hypothesis that Met-Enk may be a noncholinergic, excitatory transmitter released by field stimulation of nerves or intra-arterial motilin in the canine intestine.
Effect of gastrin-releasing peptide analogues on gastrin and somatostatin release from isolated rat stomach
Authors: Guo Y. S. , Mok L. , Cooper C. W. , Greeley G. H. , Thompson J. C. , Singh P.
Published: December 2017

A differential biological potency of bombesin (BBS), compared with its mammalian counterpart gastrin-releasing peptide (GRP), has been reported in several biological systems in rodents. In the present study we have examined the relative potency of BBS, GRP-(1-27) (GRP-L), and GRP-(14-27) (GRP-S) on the release of gastrin and somatostatin (SRIF) from the isolated perfused rat stomachs. Male rats were fasted overnight and the stomachs perfused via the celiac artery. Increasing doses of BBS, GRP-L, and GRP-S were perfused for 15 min each and the effluent collected for measurement of gastrin and SRIF. The release of gastrin and SRIF in response to the GRP analogues was biphasic, with a peak increase occurring within the first 5 min, followed by a sustained increased secretion. The release of gastrin in response to 10(-10)-10(-9) M concentrations of the peptides was strongest with GRP-S (1.5-2.0 times higher than that released by BBS and GRP-L), although at higher concentrations (10(-8) M), the response to all three analogues was similar. The release of SRIF, on the other hand, was significantly higher in the presence of BBS compared with that in response to GRP-S, while GRP-L was ineffective. These studies indicate that the biological potency of BBS compared with its mammalian counterpart, GRP, is different on the two cell populations [gastrin (G) and SRIF (D)].
Uncoupling of the secretory pathways for IgA and secretory component by cholestasis
Authors: Kloppel T. M. , Hoops T. C. , Gaskin D. , Le M.
Published: December 2017

Circulating polymeric immunoglobulin A (IgA) binds to secretory component (SC) on the surface of rat hepatocytes and is internalized and transported by vesicles to the canalicular membrane where the IgA-SC complex is secreted into bile. To further characterize this transport pathway, we examined the effects of bile flow reduction or transient bile duct obstruction on the secretion of IgA and SC into bile. In response to gradually increasing resistance to bile flow, the biliary concentration of IgA decreased as bile flow decreased, whereas total biliary protein concentration was little changed. After 2 h of bile duct clamping, the amount of IgA secreted into bile during the postclamp period was decreased to one-tenth of control values. Similarly, transport of biosynthetically labeled monoclonal IgA ([3H]MoIgA) during the postclamp period was reduced three-fold. In contrast to the impairment in IgA secretion, secretion of SC continued at nearly normal levels after resumption of bile flow. The reduced transport of IgA was not due to a failure of IgA to reach the hepatocyte, a functional alteration of the IgA, or a decrease in the number of hepatic IgA receptors. Our studies indicate that secretion of IgA is sensitive to bile flow and that the biliary secretory pathways for IgA and SC are dissociated after brief periods of cholestasis.
Motor patterns of small intestine determined by closely spaced extraluminal transducers and videofluoroscopy
Authors: Ehrlein H. J. , Schemann M. , Siegle M. L.
Published: December 2017

In the canine small intestine several simple (S) and complex (C) patterns of propulsive and nonpropulsive activities were found. The nonpropulsive activity consisted of 1) stationary individual contractions (S) and 2) stationary clusters of contractions (C). Patterns leading to aboral propulsion of luminal contents were 1) propagating contractions (S), 2) propagating power contractions (S), 3) phase III of the migrating motor complex (C), and 4) migrating clusters of contractions (C). The propagation velocities of the propulsive motor patterns differed markedly; they increased in the following order: phase III, migrating clustered contractions, propagating power contractions, propagating contractions. A retrograde transport of luminal contents was produced by two different activities: 1) retrograde propagating contractions (S) and 2) retrograde power contractions (S). They were accompanied with enterogastric reflux.
Distribution and partitioning of cholesterol and beta-sitosterol in micellar bile salt solutions
Authors: Chijiiwa K.
Published: December 2017

The distribution of cholesterol and beta-sitosterol in micellar bile salt solutions was studied using an ultrafiltration technique to separate micellar aggregates from monomers present in the intermicellar aqueous phase. The partitioning and the rates of influx across the brush-border membrane of these two sterols from micellar solutions were determined using polyethylene discs and everted jejunal sacs, respectively. Micellar solubilities of cholesterol and beta-sitosterol were not significantly different, whereas the monomer concentration of beta-sitosterol in the intermicellar aqueous phase was significantly lower than that of cholesterol [0.21 +/- 0.02 microM for beta-sitosterol and 25.0 +/- 2.71 (SE) microM for cholesterol, P less than 0.001]. There was no difference in the partitioning nor was there a difference in the rates of influx between cholesterol and beta-sitosterol from micellar solutions containing a similar amount of the two sterols. It is concluded that monomer concentration of beta-sitosterol in the intermicellar aqueous phase is extremely low compared with that of cholesterol, but their partitioning and rates of influx across the membrane are similar. This is primarily attributable to a much higher membrane/monomer partition coefficient of beta-sitosterol than cholesterol and to a direct interaction between micelle and membrane.