bluuebunny/crossref_metadata_2025 huggingface dataset:
Impaired acetylcholine release from the myenteric plexus of Trichinella-infected rats
Authors: Collins S. M. , Blennerhassett P. A. , Blennerhassett M. G. , Vermillion D. L.
Published: December 2017

We examined the release of acetylcholine (ACh) from jejunal longitudinal muscle-myenteric plexus preparations in noninfected control rats and in rats infected 6, 23, or 40 days previously with Trichinella spiralis. ACh release was assessed by preincubating the tissue with [3H]choline and measuring the evoked release of tritium. The uptake of 3H was significantly less in tissue from T. spiralis-infected rats compared with control. In tissues from either infected or control animals, electrical field stimulation (30 V, 0.5 ms, 10 Hz for 1 min), or veratridine (6-30 microM) induced 3H release that was tetrodotoxin sensitive. Depolarization by KCl (25-75 mM) also caused 3H release, but this was only partially reduced by tetrodotoxin. Radiochromatographic analysis indicated evoked release of 3H to be almost entirely [3H]ACh. In rats infected 6 days previously with T. spiralis, [3H]ACh release induced by KCl, veratridine, and field stimulation were decreased at least 80%. The suppression of [3H]ACh release induced by veratridine or KCl was fully reversible after 40 days postinfection, but field-stimulated responses remained approximately 50% of control values. These results indicate that T. spiralis infection in the rat is accompanied by a reversible suppression of ACh release from the longitudinal muscle-myenteric plexus of the jejunum.
Role of endogenous cholecystokinin on vagally stimulated pancreatic secretion in dogs
Authors: Kim C. K. , Lee K. Y. , Wang T. , Sun G. , Chang T. M. , Chey W. Y.
Published: December 2017

Pancreatic exocrine secretion was evoked by electrical stimulation of the vagus nerves (EVS) in dogs to determine whether a gut hormone was responsible for the pancreatic stimulatory activity. In 39 dogs, pancreatic juice was continuously collected to measure volume, bicarbonate, and amylase output, while portal and femoral venous plasma concentrations of gastrin, cholecystokinin (CCK), vasoactive intestinal polypeptide (VIP), and pancreatic polypeptide (PP) were determined by radioimmunoassay. EVS produced a significant increase in the pancreatic secretion. Although concentrations of all four peptides significantly increased in plasma, only CCK at the concentration in venous circulation was bioactive in dispersed rat pancreatic acini preparations. This bioactivity of CCK was completely blocked by CR 1409, a CCK-receptor antagonist. The pancreatic secretion by EVS was reduced significantly by intravenous MK-329 (formerly L364,718) to as low as 22% of control values and was completely suppressed by intravenous atropine. The increment in plasma CCK by EVS was also significantly suppressed by atropine. The present study indicates that increased pancreatic secretion by EVS is in part mediated by endogenous CCK.
Catecholamines relax portal and mesenteric veins from normal and portal hypertensive rats
Authors: Kaumann A. J. , Groszmann R. J.
Published: December 2017

The relaxation by catecholamines of superior mesenteric veins and portal veins, precontracted by 65 mM KCl, was studied after a 2-h exposure to phenoxybenzamine. The veins were obtained from portal-hypertensive and sham-operated rats. The beta 2-selective antagonist ICI 118551 attenuated the relaxation caused by epinephrine and isoproterenol but did not change the relaxation caused by norepinephrine in superior mesenteric veins. The beta 1-specific antagonist CGP 20712A reduced the relaxation caused by norepinephrine but only marginally attenuated those caused by epinephrine and isoproterenol in superior mesenteric veins. The combination of ICI 118551 and CGP 20712A abolished the relaxation caused by the catecholamines in superior mesenteric veins. The relaxation caused by norepinephrine, epinephrine, and isoproterenol was markedly reduced by ICI 118551 in portal veins. The pattern of antagonism was similar in veins from portal-hypertensive and sham-operated rats. The results suggest that both beta 1- and beta 2-adrenoceptors mediate relaxation induced by catecholamines in superior mesenteric veins. Relaxation of portal veins appears to be mediated mostly by beta 2-adrenoceptors.
Metabolism of enkephalin in stomach wall of rats
Authors: Bunnett N. W. , Walsh J. H. , Debas H. T.
Published: December 2017

Peptidases degrade neuropeptides and thereby limit the duration and extent of their influence. This investigation examined the importance of peptidases in the degradation of the neuropeptide enkephalin in the stomach wall of the rat. Metabolism of [Leu5]- and [D-Ala2][Leu5]enkephalin by gastric membranes was examined in vitro. Degradation of [Tyr1-3H][Leu5]enkephalin was studied in the gastric submucosa of anesthetized and conscious rats in vivo by using a catheter to deliver peptide to tissues and implanted dialysis fibers to collect the metabolites. Specific inhibitors were used to assess the contribution of particular enzymes. [Leu5]- and [Tyr1-3H][Leu5]enkephalin were metabolized by membranes and in the stomach wall by hydrolysis of the Tyr1-Gly2 bond. Degradation was inhibited by the aminopeptidase inhibitor amastatin (10(-5) M in vitro, 10 nmol in vivo). Inhibitors of endopeptidase-24.11 (phosphoramidon) and angiotensin-converting enzyme (captopril) did not inhibit degradation. Metabolism of the aminopeptidase-resistant analogue [D-Ala2][Leu5]enkephalin by membranes was unaffected by amastatin and weakly inhibited by phosphoramidon affected by amastatin and weakly inhibited by phosphoramidon and captopril. A carboxypeptidase removed the COOH-terminal leucine residue and made a substantial contribution to degradation of both peptides by gastric membranes.
Movement of wax particles by contractions in the isolated opossum esophagus
Authors: Ren J. , Schulze-Delrieu K.
Published: December 2017

We investigated whether the contractions of the isolated smooth muscle opossum esophagus can propel luminal contents. Wax particles were placed into the esophagus in vitro, and esophageal contractions were evoked by stimulating either primarily the intrinsic esophageal nerves (using electrical pulses of 0.5 ms) or the esophageal muscle directly (using pulses of 0.5 s). Direct muscle stimulation and neural stimulation produced circular muscle contractions of similar amplitude, but only neural stimulation was associated with a propagating ring contraction and longitudinal muscle contraction. Movement of the wax particle occurred after 21% of all stimulus responses. Aborad movement of the wax particle was 10 times as common as was its orad movement. Wax movement occurred less commonly and over shorter distance with muscle as compared with neural stimulation. The distance the wax moved was enhanced when the esophagus was allowed to shorten in its longitudinal axis. Movement occurred late during the contraction response and at velocities less than that of the ring contraction. Also, the ring contraction passed over the particle. The amplitude of circular muscle contractions had no predictive value for the occurrence of propulsion. The finding that the isolated esophagus can propel luminal contents in the aborad direction supports the thesis that peristalsis is primarily a function of the intrinsic neuromuscular organization of the smooth muscle esophagus.
Neural control of duodenal motor inhibition by antral contractions in dogs
Authors: Reddy S. N. , Daniel E. E.
Published: December 2017

The mechanism of the inhibition of proximal duodenal motor activity by carbachol-induced antral contractions or by field stimulation was studied in anesthetized dogs that had strain gauges sutured 5 and 10 cm from the pylorus on the antrum and duodenum. The duodenum was excited by vagal stimulation or distal duodenal field stimulation. Duodenal inhibition was studied 1) during a control period and after the pylorus was transected followed by administration of phentolamine, 2) during control and after phentolamine followed by pyloric transection, 3) during control and after prazosin followed by yohimbine, and 4) during control and after yohimbine. Duodenal inhibition was greater when the antral stimulation or duodenal contractions were near the pylorus. Pyloric transection did not significantly reduce this inhibition; phentolamine then abolished it. Prazosin did not abolish inhibition but yohimbine did. In conclusion, antroduodenal inhibition under our experimental conditions was mediated primarily by sympathetic nerves modulating the activity of duodenal cholinergic nerves, which possess alpha 2-adrenoceptors, and to a less extent by intrinsic nerves crossing the pylorus.
Gastric emptying of nondigestible solids in dogs: a hydrodynamic correlation
Authors: Sirois P. J. , Amidon G. L. , Meyer J. H. , Doty J. , Dressman J. B.
Published: December 2017

The influence of particle size, particle density, fluid viscosity, and fluid flow rate on the gastric emptying of nondigestible solids was investigated in five dogs with chronically placed fistulas. Six hundred and fifty particles of 13 different size and density combinations were administered simultaneously with 500 ml of either normal saline or low-, medium-, or high-viscosity polymer solutions. The canine stomach was found to discriminate between these solids on the basis of size and density at all levels of viscosity above saline. The observed patterns of emptying are consistent with the hypothesis that gastric emptying of nondigestible solids is governed in part by hydrodynamics and correlate well with the gastric-emptying coefficient (GEC), a dimensionless grouping of variables that takes the form GEC = (Dpy/Dp) [g(rho f - rho p)Dp2]/[eta (nu)] where [g(rho f - rho p)] is particle buoyancy consisting of fluid (rho f) and particle (rho p) densities and g, the gravitational constant; (Dp) is the particle diameter, (Dpy) the estimated pyloric diameter, eta the fluid viscosity, and (nu) the average linear velocity of fluid exiting the stomach.
Contribution of Cl(-)-OH- exchange to electroneutral NaCl absorption in rat distal colon
Authors: Foster E. S. , Dudeja P. K. , Brasitus T. A.
Published: December 2017

Neutral NaCl absorption is the predominant Na+ absorptive process in rat distal colon. Whether this neutral NaCl absorptive process represents Na(+)-Cl- cotransport or dual ion exchanges of Na(+)-H+ and Cl(-)-OH- has been uncertain. Recent studies using rat colonic brush-border membrane vesicles (BBMVs) have described a Na(+)-H+ exchange mechanism and have proposed that net NaCl absorption occurs via a dual ion exchange process. To date, however, an anion exchanger on the colonic apical membrane has not been identified. To determine whether a Cl(-)-OH- exchange process is present, 36Cl uptake was evaluated across rat distal colonic BBMVs. A pH gradient (7.7 in/5.5 out) stimulated active Cl- uptake. Cl- uptake was not significantly affected by the presence of a valinomycin-induced K+ diffusion potential (inside positive), suggesting that a Cl- conductive pathway is not present in these membranes. The pH gradient-stimulated Cl- uptake was a saturable function of the Cl- concentration with a Km of 14.3 +/- 5.0 mM and a Vmax of 20.4 +/- 5.5 nmol.mg protein-1.30 s-1 and was almost completely inhibited by 1 mM concentrations of SITS and DIDS, inhibitors of anion exchange processes in other epithelia. Inward gradients of Na+, K+, or Na+ and K+ did not further stimulate initial Cl- uptake, suggesting that coupling of Na+ and Cl- movement does not occur by a cotransport mechanism. Thus a Cl(-)-OH- exchange process is present in rat distal colonic BBMVs.(ABSTRACT TRUNCATED AT 250 WORDS)
Mechanical aspects of rabbit fecal dehydration
Authors: McKie A. T. , Powrie W. , Naftalin R. J.
Published: December 2017

The hydrostatic pressure required to reduce the water content of rabbit feces in an odometer from greater than 80 to less than 65% was approximately 5 atm. This pressure was unaffected by raising the temperature from 20 to 37 degrees C. It became progressively more difficult to dehydrate feces as consolidation occurred, as is evident from the significant (P less than 0.001) reduction in the fecal consolidation coefficient (Co) from 1.76 +/- 0.25 X 10(-6) (n = 4) to 1.35 +/- 0.093 X 10(-7) m2/s (n = 4) and the fecal fluid permeability coefficient (k) from 4.10 +/- 0.51 X 10(-8) (n = 4) to 1.42 +/- 0.12 X 10(-10) m/s (n = 4), concomitant with the reduction in fecal water content. The results suggest that rabbit hard feces are unlikely to be produced, under physiological conditions, by mechanical pressure exerted by the wall of the colon or by a prolonged retention time of hard feces by the distal colon. The hypertonic absorbate (1,000 mosmol/kg) produced by rabbit descending colon is of sufficient magnitude to overcome the fecal resistance to dehydration.
An orally active inhibitor of leukotriene synthesis accelerates healing in a rat model of colitis
Authors: Wallace J. L. , Keenan C. M.
Published: December 2017

Leukotrienes (LTs) have been implicated as mediators of the inflammation and ulceration associated with ulcerative colitis and Crohn's disease. In the present study, the effects of a novel, orally active inhibitor of LT synthesis (MK-886) were examined in a rat model of chronic colitis. Colitis was induced by intracolonic administration of trinitrobenzenesulfonic acid. Colonic LTB4 synthesis was measured after incubation of tissue samples in vitro and by in vivo equilibrium dialysis. A single dose of MK-886 (10 mg/kg) significantly inhibited colonic LTB4 synthesis for greater than 24 h. Daily treatment with this dose significantly reduced colonic damage, as assessed macroscopically and histologically, when the treatment was performed 2 h before induction of colitis and daily thereafter for 1 wk, but not when treatment was performed during the second week after induction of colitis. A less marked beneficial effect of MK-886 was observed when the pretreatment dose was excluded, suggesting a role for LTs in the early events of the inflammatory process. Inhibition of LT synthesis during the first 24 h after induction of colitis did not alter the extent of infiltration of neutrophils into the colon, as measured by tissue myeloperoxidase activity. Daily treatment with sulfasalazine (100 mg/kg po) either during the first or second week after induction of colitis did not significantly affect the rates of healing. At the dose used, sulfasalazine only produced a transient inhibition of colonic LTB4 synthesis. This study therefore demonstrates that a specific, orally active inhibitor of LT synthesis can significantly accelerate healing in this animal model of colitis when the treatment is performed during the early phase of the inflammatory response.
Regulatory volume increase in mammalian jejunal villus cells is due to bumetanide-sensitive NaKCl2 cotransport
Authors: MacLeod R. J. , Hamilton J. R.
Published: December 2017

We assessed ion transport mechanisms operative during regulatory volume increase (RVI) in villus enterocytes isolated in suspension from guinea pig jejunum and examined with electronic cell sizing and 86Rb influx. After validation of the electronic-sizing technique with direct measurements of cell water, the response of cell volume to hypertonic media was evaluated in detail. When shrunk by exposure to hyperosmotic media (455 mosmol/kg medium) cells demonstrated a RVI that was complete in 20 min. RVI required extracellular Na+, K+, and Cl-; this cell swelling showed the following ion sensitivity; Na+ greater than Li+ greater than choline, K+ = Rb+, and Cl- greater than or equal to Br- greater than NO3- = acetate = gluconate. Bumetanide inhibition of villus cell swelling was concentration dependent from 10(-10) to 10(-5) M (7.0 +/- 4.5% vs. 87.8 +/- 0.3%); furosemide (10(-3)M) inhibited RVI (74.1 +/- 9.5%), but amiloride (10(-4) M) had little effect on cell swelling. Disulfonic stilbenes, 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (10(-4) M), generated the same inhibition of RVI in either nominally HCO3(-)-free phosphate-buffered saline (PBS) or HCO3(-)-buffered PBS, suggesting anion exchange was not involved. Ouabain (10(-4) M) stimulated cell swelling. Hypertonic shrinkage increased the initial rate of bumetanide-sensitive 86Rb influx (80 +/- 38 vs. 1,011 +/- 241 pmol.mg protein-1.min-1; P less than 0.005) and required extracellular Na+ and Cl- (11 +/- 16 vs. 28 +/- 61 pmol.mg protein-1.min-1). RVI was prevented in low-K+ media (0.2 mM), but the addition of KCl initiated cell swelling. Our data strongly suggest that RVI in jejunal villus enterocytes occurs because of the hypertonic activation of NaKCl2 cotransport.
Effects of inhibition of gastric secretion on antral gastrin and somatostatin gene expression in rats
Authors: Wu S. V. , Giraud A. , Mogard M. , Sumii K. , Walsh J. H.
Published: December 2017

Antral gastrin and somatostatin mRNA concentrations were measured in rats during gastric neutralization produced either by resection of the acid-secreting portion of the stomach (fundectomy) or by omeprazole treatment. Fundectomy caused increases in gastrin mRNA concentrations to 570% of sham control after 4 days and to 650% after 28 days. Daily administration of omeprazole resulted in significant dose- and time-dependent increases in antral gastrin mRNA concentrations. Four-day treatment with omeprazole caused threefold increased gastrin mRNA. Antral somatostatin mRNA concentrations decreased significantly after fundectomy to 66% of sham control after 4 days and to 23% after 28 days. Omeprazole produced a more profound decrease in somatostatin mRNA to 22% of the vehicle control after 4 days. Antral beta-actin mRNA concentrations did not differ significantly between control and experimental animals. Transcription of gastrin mRNA in isolated antral mucosal nuclei, measured by a nuclear run on technique, was significantly increased after omeprazole treatment in vivo. Increases in plasma and antral gastrin concentrations in response to gastric neutralization were closely associated with increases in gastrin mRNA and were accompanied by reductions in somatostatin mRNA in the antrum. However, fundectomy produced relatively greater increases in gastrin mRNA and lesser reductions in somatostatin mRNA than observed after omeprazole pretreatment.
Serum factors influencing cultured hepatocyte exogenous and endogenous triglyceride
Authors: Levinson M. , Oswald B. , Quarfordt S.
Published: December 2017

Rat hepatocyte monolayer triglyceride content was increased modestly by incubations with apolipoprotein E-containing triglyceride emulsions or chylomicrons (exogenous) and was increased substantially by increasing media free fatty acid concentrations (endogenous). The secretion of both endogenous and exogenous triglyceride into media was enhanced by additions of serum and serum components. These additions not only enhanced hepatocyte triglyceride secretion but also, because of the absence of media lipolysis, more triglyceride was recovered in the system. Lipoprotein-free serum replicated the effect of whole serum. Lipoprotein produced a more modest secretory response. The apolipoprotein C components were the only ones that enhanced hepatic triglyceride secretion. Both lipoprotein-free plasma and lipoprotein enhanced the in vitro transfer of hepatocyte exogenous triglyceride to fibroblast.
Variations in duodenal cross-sectional area during the interdigestive migrating motility complex
Authors: Gregersen H. , Kraglund K. , Djurhuus J. C.
Published: December 2017

A probe for measurement of intestinal cross-sectional area (CA) was used to elucidate variations of human gut CA during the interdigestive migrating motility complex (MMC). A balloon was inflated by saline at a pressure of 1 kPa, and variations of balloon CA (BCSA) were measured by means of the field-gradient principle. Duodenal phasic activity was measured by perfused side holes proximal to, distal to, and inside the balloon. In vitro characterization of probe performance showed that static measurement of BCSA was very accurate regardless of the configuration of the balloon. However, during dynamic measurements, BCSA was valid only for slow variations in BCSA due to resistance in the evacuation and inflation system. Eight duodenal MMCs were recorded. BCSA increased consistently from the start of phase I to the end of phase II from 72 (45-100) to 136 (87-154) mm2. During late phase II, a large BCSA increase was recorded. A positive correlation between the phasic activity level in phases I and II of MMC and maximal BCSA in duodenum was demonstrated (proximal P less than 0.01; distal P less than 0.05). BCSA during phase III was small but could not be estimated accurately because steady-state conditions were not obtained. The large BCSA in late phase II suggests a relaxation of the duodenal wall secondary to a decrease in smooth muscle tone. The results add evidence to previous findings of a low-resistance or large-capacitance situation in late phase II, observed as a large pancreaticobiliary excretion into the duodenum and an increased flow of duodenal contents.
Luminal CCK-releasing factors in the isolated vascularly perfused rat duodenojejunum
Authors: Cuber J. C. , Bernard G. , Fushiki T. , Bernard C. , Yamanishi R. , Sugimoto E. , Chayvialle J. A.
Published: December 2017

The factors operating at the apical side of the endocrine cell releasing cholecystokinin (CCK) were investigated using the isolated vascularly perfused rat duodenojejunum. In the protease-free intestinal segment, a 30-min infusion of glucose (280 mM), oleic acid (100 mM), or triglycerides containing short- or long-chain fatty acids did not alter significantly the basal level of portal CCK-like immunoreactivity (CCK-LI), while octanoic acid (100 mM) produced a transient rise of plasma CCK-LI to approximately 250% of basal. Infusion of proteins (5% solutions of ovalbumin or casein) or of a mixture of all amino acids brought about a modest CCK secretion. In contrast, isocaloric amounts of an ovalbumin hydrolysate produced a sharp rise of portal CCK-LI to 530% of basal followed by a well-sustained plateau secretion (420% of basal) until the end of the infusion. An acid casein hydrolysate induced a slightly less pronounced CCK-LI release and was followed in decreasing order by meat, casein, and soybean peptones. Simultaneous infusion of trypsin with ovalbumin or casein hydrolysate reduced by approximately 60% the CCK release induced by peptone alone. This effect was reversed by coinfusion of soybean trypsin inhibitor (SBTI) with the trypsin-peptone mixture. Arterial infusion of tetrodotoxin (10(-6) M) or atropine (10(-5) M) had no significant effect on the trypsin-induced inhibition of peptone-mediated CCK-LI release. Administration of SBTI or camostate alone or in combination with trypsin did not alter basal CCK. Monitor peptide produced a dose-dependent transient rise of portal CCK-LI over the range from 2 to 12 micrograms.(ABSTRACT TRUNCATED AT 250 WORDS)
Response of canine lower esophageal sphincter to gastric distension
Authors: Franzi S. J. , Martin C. J. , Cox M. R. , Dent J.
Published: December 2017

The aim of this study was to localize the region of the stomach responsible for triggering distension-induced transient lower esophageal sphincter relaxation (TLESR). The canine stomach was partitioned into subsegments by a row of buttressed sutures. This separated either the fundus from the lesser curve or the proximal stomach from the antrum. After 1 mo each region was progressively distended while gastroesophageal pressures were monitored. At the time of the first TLESR, gastric wall tension was estimated from the bag pressure and volume. Distension of the intact stomach, lesser curve, or proximal stomach in 12 dogs produced a progressive increase in lower esophageal sphincter (LES) pressure, which was interrupted at low gastric wall tension (29, 35, and 40 mmHg.cm, respectively) by a superimposed TLESR. Background LES pressure fell progressively with distension of the antrum but was unchanged by distension of the fundus alone. Both the fundus and antrum had significantly higher thresholds for triggering TLESR (96 and 105 mmHg.cm). In another two dogs truncal vagotomy performed at the time of gastric partitioning prevented both the change in background LES pressure, and the triggering of TLESR, associated with proximal gastric and antral distension. We conclude that the subcardiac region of the stomach is primarily responsible for triggering TLESR induced by distension and that the effect on background LES pressure depends on the region distended.
A comparison of absorption of glycerol tristearate and glycerol trioleate by rat small intestine
Authors: Bergstedt S. E. , Hayashi H. , Kritchevsky D. , Tso P.
Published: December 2017

Generally, fats rich in saturated fatty acids raise serum cholesterol, whereas fats rich in polyunsaturated fatty acids lower it. There appear to be exceptions; e.g., stearic acid (18:0)-rich fats have little or no effect on serum cholesterol concentrations. This apparent lack of cholesterolemic effect of stearic acid-rich fat could be because intestinal absorption of fat is poor or subsequent plasma and/or tissue metabolism of fat is different. To investigate mechanisms involved, we compared intestinal digestion, uptake, and lymphatic transport of glycerol tristearate (TS) and glycerol trioleate (TO, 18:1). Two groups of rats bearing intestinal lymph fistulas were used. TO rats were fed intraduodenally for 8 h at a constant rate a lipid emulsion of 25 mumols/h of TO (labeled with glycerol tri[9,10 (n)-3H]oleate), 7.8 mumols of egg phosphatidylcholine, and 57 mumols of sodium taurocholate in 3 ml of phosphate-buffered saline. TS rats were fed the same lipid emulsion except that TS replaced TO and the emulsion was labeled with glyceryl [1,3-14C]tristearate. The lymph triglyceride and radioactivity were determined. After infusion, the luminal and mucosal radioactive lipid content was analyzed. The results showed that there was significantly less lipid transported in the lymph of TS rats compared with TO rats. The results also showed a significant decrease in the absorption of TS as compared with TO. This was due in part to poor lipolysis. In addition, the lipid absorbed by the intestine of the TS rats was transported into lymph less efficiently than in TO rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Ethanol enhances leukocyte-endothelial cell interactions in mesenteric venules
Authors: Kvietys P. R. , Perry M. A. , Gaginella T. S. , Granger D. N.
Published: December 2017

In vivo studies have implicated neutrophils in the gastric mucosal injury produced by intraluminal administration of ethanol. However, in vitro studies indicate that ethanol inhibits various neutrophil functions such as adherence, chemotaxis, and degranulation. The aim of the present study was to assess whether ethanol, at clinically relevant concentrations, is proinflammatory in vivo. Ethanol (0.2, 1.0, 2.0, and 4.0%) was applied to the surface of the cat mesentery, and neutrophil adherence to venules (30 microns diam) and extravasation into the interstitium were quantitated using intravital microscopy. Hemodynamic parameters were also measured (venular diameter, red blood cell velocity, and leukocyte rolling velocity) or calculated (venular blood flow and wall shear stress). In this model ethanol produced a dose-dependent increase in neutrophil adherence and extravasation. The increase in leukocyte-endothelial cell interactions could not be attributed to alterations in hemodynamic factors. Pretreatment of animals with a monoclonal antibody (MoAb IB4) directed to the neutrophil CD11/CD18 adherence complex completely prevented the ethanol-induced neutrophil adherence and extravasation. Pretreatment with a leukotriene B4 (LTB4)-receptor antagonist (SC 41930) or a platelet-activating factor (PAF)-receptor antagonist (WEB 2170) did not alter the ethanol-induced neutrophil-endothelial interactions. We conclude that ethanol is proinflammatory at concentrations which may be achieved in the mucosal interstitium during acute alcohol intoxication. The ethanol-induced leukocyte adherence and extravasation is dependent on the expression of adhesive glycoproteins. The inflammatory mediators, PAF and LTB4, do not appear to play an important role in the leukocyte-endothelial cell interactions initiated by ethanol.
Vitamin D-independent intestinal calcium and phosphorus absorption during reproduction
Authors: Brommage R. , Baxter D. C. , Gierke L. W.
Published: December 2017

A special metabolic cage system was employed to measure the intestinal, renal, and mammary gland fluxes of Ca, P, and Mg in vitamin D-deficient rats during late pregnancy and lactation. Dietary Ca, P, and Mg levels were 0.78, 0.34, and 0.083%, respectively; this diet minimizes the reduction in milk production observed during vitamin D deficiency. Compared with identically treated virgin rats, lactating rats were slightly hypocalcemic and severely hypophosphatemic. Hypertrophy of the small intestine, as indicated by increased intestinal length and villus height, occurred during lactation. Net fractional intestinal absorption of Ca and P, but not Mg, was elevated twofold during late pregnancy and throughout lactation. Despite this elevated intestinal absorption, lactating rats were in negative Ca and P balance and lost bone mass. The transfer rates of Ca, P, and Mg into milk were approximately 77% of values previously observed in vitamin D-replete rats. Lactating rats conserved P by dramatically reducing renal P excretion. Pup retention of ingested Ca was virtually complete. These results, together with previous observations using everted duodenal gut sacs, indicate that there is a vitamin D-independent stimulation of intestinal Ca and P absorption during pregnancy and lactation. Because fractional Mg absorption was not similarly enhanced, this stimulation shows some specificity.
Effect of T. spiralis infection on intestinal motor activity in the fasted state
Authors: Cowles V. E. , Sarna S. K.
Published: December 2017

We sought to determine the effects of Trichinella spiralis infection on small intestinal motor activity in the fasted state in dogs and relate it to clinical symptoms during the intestinal phase of trichinosis. Motor activity was recorded by strain gauge force transducers. Infection with T. spiralis resulted in a significant increase in the incidence and proximal origination of giant migrating contractions (GMCs) during the first 5 days postinfection. This was also the time when the dogs had diarrhea. The dogs were often restless and showed signs of discomfort during proximally originating GMCs. The incidence of retrograde giant contractions (RGCs) increased significantly on the 2nd and 3rd day postinfection. RGCs were followed by vomiting 71% of the time during infection. The migrating motor complex cycle length increased significantly, and this was due to intestinal "amyogenesia" and "dysmyogenesia". During these phenomena, electrical control activity was almost completely obliterated in the proximal half of the small intestine (amyogenesia) and became irregular and unstable in the distal half (dysmyogenesia). Intestinal amyogenesia and dysmyogenesia lasted up to 4 h and were terminated by a GMC. We conclude that diarrhea induced by T. spiralis infection is closely associated with an increase in the incidence and proximal origin of GMCs. These GMCs may also be the motor correlates of abdominal cramping and pain during the intestinal phase of trichinosis.
Transport of biotin in basolateral membrane vesicles of rat liver
Authors: Said H. M. , Korchid S. , Horne D. W. , Howard M.
Published: December 2017

We examined biotin transport across the basolateral membrane (BLM) of rat liver using BLM vesicles (BLMV) technique. The purity and suitability for transport studies of liver BLMV were demonstrated by morphological (electron microscopy), enzymatic, and functional criteria. Orientation of liver BLMV was determined by freeze-fracture electron microscopy and by [3H]ouabain binding methodology and was found to be 65.3-69.7% in the right-side-out orientation. Uptake of biotin by liver BLMV was found by osmolarity and temperature studies to be mostly the result of transport of the substrate into an active intravesicular space with little binding to membrane surfaces. Transport of biotin was found to be Na+ gradient dependent with a distinct "over-shoot" phenomenon. Initial rate of transport of biotin as a function of concentration was found to include a saturable component in the presence of a Na+ gradient (out greater than in) but was linear and lower in the presence of a K+ gradient (no Na+). Kinetic parameters of the saturable Na+ gradient-dependent transport process were 0.39 microM and 1,807 fmol.mg protein-1.20 s-1 for the apparent Km and Vmax, respectively. In the presence, but not the absence, of a Na+ gradient (out greater than in), the addition of structural analogues to the incubation medium caused significant inhibition in the transport of 0.079 microM [3H]biotin. Induction, with the use of valinomycin and an inwardly directed K+ gradient, of a relatively positive intravesicular space caused significant inhibition in the initial rate of biotin transport.(ABSTRACT TRUNCATED AT 250 WORDS)
Stimulation of acetylcholine release in myenteric plexus by calcitonin gene-related peptide
Authors: Mulholland M. W. , Jaffer S.
Published: December 2017

The effects of calcitonin gene-related peptide (CGRP) on acetylcholine (ACh) release from myenteric plexus neurons in primary culture were investigated. CGRP (10(-12) to 10(-6) M) produced a dose-dependent increase in [3H]ACh release. The ACh release caused by CGRP was significantly inhibited (74 +/- 24%) by preincubation with dideoxyadenosine but was increased more than threefold by preincubation with theophylline. Incubation of myenteric plexus neurons with CGRP (10(-8) M) in the presence of diltiazem (10(-5) M) or in a calcium-free medium markedly reduced [3H]ACh release. CGRP potentiated [3H]ACh release stimulated by potassium or substance P but not by cholecystokinin octapeptide or forskolin. The results demonstrate that CGRP cause release of ACh from guinea pig myenteric plexus neurons and suggest that the peptide acts through an adenosine 3',5'-cyclic monophosphate-dependent mechanism that involves neuronal calcium channels.
Cation current activated by hyperpolarization (IH) in guinea pig enteric neurons
Authors: Galligan J. J. , Tatsumi H. , Shen K. Z. , Surprenant A. , North R. A.
Published: December 2017

Intracellular microelectrode and whole cell patch-clamp recordings were made from guinea pig enteric neurons in vitro. In most myenteric AH neurons (but not S neurons), step hyperpolarizations from the resting potential evoked an inward current (IH). IH peaked in approximately 400 ms (at 36 degrees C), was fully activated at -100 mV, and did not inactivate during 10 s. IH was associated with a conductance increase and reversed polarity at about -40 mV (by extrapolation). IH was reduced in low-sodium concentrations and increased when the concentration of extracellular potassium ions was increased. Cesium (2 mM) blocked IH in a voltage-dependent manner; this led to an increase in the amplitude of the spike after-hyperpolarization. Cobalt (2-4 mM) or barium (0.01-1 mM) did not alter IH. Only 12% of submucous plexus neurons showed IH and this subgroup included both S and AH neurons. In myenteric AH neurons, IH would act in opposition to the persistent calcium-activated potassium current and thus stabilize the resting potential.
Inositol phosphate formation and [Ca2+]i in secretagogue-stimulated rabbit gastric mucous cells
Authors: Seidler U. , Pfeiffer A.
Published: December 2017

The formation of inositol phosphates and the changes in free intracellular Ca2+ ([Ca2+]i) in isolated rabbit gastric mucous cells during cholinergic stimulation were examined and the potential role of inositol phosphate turnover and [Ca2+]i in gastric mucus secretion evaluated. Rabbit chief and parietal cells were studied for comparison. The formation of [3H]inositol phosphates in mucous, chief, and parietal cells was stimulated in a time- and concentration-dependent fashion by acetylcholine (ACh). The ACh-induced initial [Ca2+]i peak was maximally (10(-4) M ACh) 199 +/- 8% of basal in mucous cells, 427 +/- 20% in chief, and 455 +/- 31% in parietal cells and was followed by a lower-level plateau in mucous and parietal cells but by a more rapid decline in chief cells. As in parietal and chief cells, the initial [Ca2+]i peak occurred in mucous cells in the absence of external Ca2+. ACh stimulated a mucous cell membrane Ca2(+)-entry mechanism in addition to release of Ca2+ from intracellular stores. The concentration-response relationships for the production of [3H]-inositol phosphates, the initial rise in [Ca2+]i, and the stimulation of glycoprotein secretion by ACh were virtually identical. Suppression of the [Ca2+]i rise by the intracellular Ca2(+)-chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) abolished the secretory response. As with many other secretory cells, gastric mucous cells possess cholinergic receptors that upon stimulation mediate the hydrolysis of phosphoinositides, a release of Ca2+ from intracellular stores, and a stimulation of Ca2+ influx through the plasma membrane.
Regulation of acid secretion by bombesin/GRP neurons of the gastric fundus
Authors: Schubert M. L. , Hightower J. , Coy D. H. , Makhlouf G. M.
Published: December 2017

Intramural neurons in the fundus of the isolated mouse stomach were activated by 1,1-dimethyl-4-phenylpiperazinium (DMPP) or by electrical field stimulation and the participation of cholinergic and bombesin/gastrin-releasing peptide (GRP) neurons in the regulation of acid secretion evaluated with atropine and a selective bombesin/GRP antagonist, [Leu13-psi(CH2NH)-Leu14]bombesin. For both DMPP and field stimulation, atropine inhibited acid secretion and augmented somatostatin secretion. The bombesin/GRP antagonist had an opposite effect, augmenting acid secretion and inhibiting somatostatin secretion to below basal levels. The combination of the two antagonists restored DMPP- and field-stimulated acid and somatostatin secretion to basal levels. The results indicate that neurally stimulated acid secretion in the isolated mouse stomach is regulated by cholinergic neurons that mediate stimulation and bombesin/GRP neurons that mediate inhibition of acid secretion. Cholinergic neurons exert their stimulatory effect by acting directly on parietal cells and indirectly by eliminating the inhibitory influence of somatostatin. Bombesin/GRP neurons exert their inhibitory effect mainly by inducing release of somatostatin; an additional direct inhibitory effect of bombesin/GRP neurons on parietal cells is possible.
Volume regulation initiated by Na(+)-nutrient cotransport in isolated mammalian villus enterocytes
Authors: MacLeod R. J. , Hamilton J. R.
Published: December 2017

We assessed ion transport during regulatory volume decrease (RVD) in jejunal villus enterocytes, isolated in suspension from guinea pig jejunum and swollen by exposure to L-alanine (L-Ala) or D-glucose (D-Glc) in the presence of Na+. Cell volume was measured electronically. Relative volume of cells (rel vol: cell vol/isotonic vol) within 1 min of L-Ala (20 mM) addition increased (1.10 +/- 0.03, P less than 0.005), but by 5 min there was no difference between cells in L-Ala or 20 mM D-Ala (0.95 +/- 0.02). Cell shrinkage after maximal swelling was greater with L-Ala than with D-Ala (14 +/- 4 vs. 2 +/- 1%, P less than 0.01). Initial swelling generated by L-Ala required extracellular Na+ (P less than 0.02). Volume increased 30 s after D-Glc (20 mM), and cells were larger than cells treated with L-Glc (1.04 +/- 0.01 vs. 0.95 +/- 0.01, P less than 0.001); subsequent cell shrinkage was complete in 2 min (8 +/- 2%, P less than 0.05). Swelling generated by methyl alpha-D-glucoside was prevented by 0.1 mM phloridzin (P less than 0.05). RVD after D-Glc swelling was prevented by inhibitors of K+ channels, 5 mM Ba2+ (P less than 0.001), 100 microM quinine (P less than 0.005), or 25 mM TEA (P less than 0.02), but the same inhibitors completely prevented L-Ala swelling. All inhibitors had no effect on L-Ala uptake into brush-border membrane vesicles in presence of Na+ gradient.(ABSTRACT TRUNCATED AT 250 WORDS)
Role of CCK in regulation of pancreaticobiliary functions and GI motility in humans: effects of loxiglumide
Authors: Schmidt W. E. , Creutzfeldt W. , Schleser A. , Choudhury A. R. , Nustede R. , Hocker M. , Nitsche R. , Sostmann H. , Rovati L. C. , Folsch U. R.
Published: December 2017

To evaluate the physiological role of cholecystokinin (CCK) in humans, we studied the influence of the specific CCK receptor antagonist loxiglumide (CR 1505) on gallbladder contraction, pancreatic enzyme output, plasma CCK concentrations, mouth-to-cecum transit time (MCTT), stool weight, and fecal fat excretion. Infusion of CCK-8, producing CCK plasma levels of 10-12 pmol/l, decreased gallbladder volume to 21% of the initial volume (P less than 0.01) and increased bilirubin output 8- to 10-fold and pancreatic enzyme secretion 2- to 4-fold. Infusion of loxiglumide (10 mg.kg-1.h-1 iv) abolished CCK-8-stimulated enzyme and bilirubin output. Basal gallbladder volume increased 68% during loxiglumide infusion (P less than 0.001) and 137% (P less than 0.001) after 7 days of oral loxiglumide treatment (3 x 1.6 g/day). Gallbladder contraction and bilirubin output in response to the intraduodenal instillation of a liquid meal (382 kcal) was completely inhibited by loxiglumide; gallbladder volume even increased 45% postprandially during loxiglumide infusion (P less than 0.02) and 145% after long-term loxiglumide treatment (P less than 0.001). Meal-stimulated pancreatic enzyme output was diminished 46-53% after acute and 25-29% after chronic administration of loxiglumide. Meal-stimulated integrated plasma CCK-immunoreactive (CCK-ir) concentrations, determined by RIA, were 3.2-fold higher during loxiglumide infusion (P less than 0.02); plateau CCK levels were markedly elevated (10.1 +/- 1.4 vs. 3.7 +/- 0.5 pM). Plasma CCK-like bioactivity, measured by a sensitive bioassay, was identical to CCK-ir levels in the absence of loxiglumide; in the presence of loxiglumide, no circulating CCK-like bioactivity was detectable, indicating complete inhibition of plasma CCK. MCTT was augmented 24% (P less than 0.05). Oral treatment with loxiglumide increased stool weight 72% (P less than 0.01) and fecal fat excretion 186% (P less than 0.001). In conclusion, 1) meal-induced gallbladder contraction and fasting tone are primarily controlled by CCK; 2) the contribution of CCK to the intestinal phase of postprandial pancreatic enzyme secretion is 40-50%; 3) GI motility and absorption are partially controlled by CCK; and 4) postprandial CCK secretion is substantially augmented by loxiglumide via an unknown mechanism.
Noncholinergic membrane potential responses to transmural nerve stimulation in the guinea pig ileum
Authors: Crist J. R. , He X. D.
Published: December 2017

We sought to characterize the projections of nonmuscarinic intramural inhibitory and excitatory neural input to the circular muscle layer of the small intestine. Intracellular membrane potential recordings were made in smooth muscle cells from the distal ileum of 22 guinea pigs. Intramural nerve stimulation (4 pulses, 15 mA, 20 Hz, 2 ms) was delivered by two electrodes located at varying distances from the recording electrode along the longitudinal axis of the intestine. The membrane potential responses immediately oral to the stimulus consisted of an abrupt-onset inhibitory junction potential (IJP) followed by two distinct depolarizations, an early excitatory junction potential (EJP) and a late EJP. The early IJP and early and late EJPs were observed as far as 53 +/- 5, 56 +/- 6, and 39 +/- 5 mm oral to the stimulus, respectively. The responses immediately anal to the stimulus consisted of an initial IJP followed by a prolonged hyperpolarization, which was sometimes interrupted by a superimposed EJP. The early IJP, EJP, and late IJP were observed as far as 77 +/- 12, 66 +/- 10, and 37 +/- 13 mm anal to the stimulus, respectively. All excitatory events greater than 5-10 mm oral or anal to the stimulus were blocked by hexamethonium. Hexamethonium slightly antagonized the early IJP oral to the stimulus but had no effect on the early IJP anal to the stimulus. The late IJP was not affected by hexamethonium. These studies are the first to describe a late IJP, which is observed only at sites anal to the stimulus, and a late EJP, which is observed only at sites oral to the stimulus. The neural pathways involved in these late synaptic events (late EJP and IJP) as well as the previously described early synaptic events (early EJP and IJP) are discussed.
Sucrase-alpha-dextrinase in diabetic BioBreed rats: reversible alteration of subunit structure
Authors: Najjar S. M. , Hampp L. T. , Rabkin R. , Gray G. M.
Published: December 2017

BioBreed (BB) Wistar rats develop diabetes mellitus, which closely resembles the human disease, in 50% of progeny. Intestinal sucrase-alpha-dextrinase, a glycoprotein hydrolase of the enterocyte's brush border consisting of 140-kDa alpha-dextrinase and 125-kDa sucrase subunits, is essential for surface digestion of carbohydrate nutrients. Although its catalytic characteristics were found to be maintained in the diabetic state, the structure of the subunits, as compared with normal Wistar rats, was altered in the BB rat within 2 days of the onset of diabetes. Its capacity to react in a solid-phase immunoassay was reduced by 50%; when examined by 6% acrylamide electrophoresis, the sucrase subunit was increased in mass by 5 kDa and, in some BB rats, the dextrinase subunit was reduced by 5 kDa. Intact rats labeled intraintestinally with [35S]methionine displayed the alteration within 6 h of synthesis, indicating that nonenzymatic glycosylation could not account for the structural change. This mass change was not seen in streptozotocin-induced diabetes and was independent of the plasma glucose concentration or the degree of acidosis. Deglycosylation with peptide N-glycosidase indicated that the N-linked chains of the normal dextrinase subunit (11 kDa) have twice the mass of those in the BB rat (6 kDa) and that the sucrase subunit may have an increased mass of O-linked chains. Overall, these experiments point to changes in glycosylation as a mechanism of structural alteration in congenital diabetes. Despite persistence of the insulin-dependent diabetes, the subunit pattern eventually became indistinguishable from normal, but at differential rates (21 days and 35 days, respectively, for sucrase and dextrinase subunits).
Nitric oxide mediating NANC inhibition in opossum lower esophageal sphincter
Authors: Tottrup A. , Svane D. , Forman A.
Published: December 2017

Strips from opossum lower esophageal sphincter were prepared and mounted in organ baths for recording of isometric tension. Nonadrenergic, non-cholinergic (NANC) inhibitory responses were evoked by transmural field stimulation. The relaxant responses to field stimulation were inhibited in a concentration-dependent manner by N omega-nitro-L-arginine (L-NNA), a substance known to inhibit the formation of nitric oxide (NO). At a concentration at 10(-4) M of L-NNA, most preparations contracted during field stimulation, and this response was abolished by atropine (10(-6) M). L-Arginine (10(-5) M) shifted the concentration-response curve for L-NNA to the right. Relaxant responses to VIP (10(-9) to 10(-6)M) and sodium nitroprusside (10(-9) to 10(-5) M) were unaffected by preincubation with L-NNA (10(-5) to 10(-4) M) or L-arginine (10(-5) M). The inhibition of NANC-relaxation was apparently not due to an influence on release of a NANC transmitter different from NO, since L-NNA had no preserving effects on responses to field stimulation in preparations treated with scorpion venom. We conclude that involvement of a NO-generating process from L-arginine seems mandatory for NANC responses in the isolated lower esophageal sphincter.