bluuebunny/crossref_metadata_2025 huggingface dataset:
Myogenic regulation of propagation in gastric smooth muscle
Authors: Publicover N. G. , Sanders K. M.
Published: December 2017

Experiments were performed to test the effects of frequency and stretch on the velocity of slow wave propagation parallel and perpendicular to the long axis of circular muscle fibers in the canine gastric antrum. Slow waves were evoked from one corner of a rectangular sheet of muscle and propagated throughout the tissue. Mathematics were derived and are presented, which simultaneously compute conduction velocities in each direction, regardless of electrode positions. Increased rate of stimulation had no significant effect on conduction velocity in the circumferential axis, but propagation slowed in the axis perpendicular to the circular fibers by an average of 25% over interstimulus intervals between 12 and 60 s. Conduction velocity was also a function of the degree of stretch. The most rapid conduction velocity occurred when muscles were stretched to an average of 118% of the resting, fasted length found in situ in the axis parallel to the circular fibers and 140% in the axis perpendicular to the circular fibers. Propagation was blocked by stretching muscles past 200% of resting length. These results suggest that the frequency of slow waves and gastric distension are intrinsic mechanisms capable of regulating the spread of slow waves.
Contribution of hyperosmolality to glucose-induced intestinal hyperemia
Authors: Proctor K. G.
Published: December 2017

To test the hypothesis that changes in tissue osmolality participate in glucose-induced absorptive hyperemia, the mucosa of the rat jejunum was suffused with isotonic or hypertonic glucose solutions. Blood flow was calculated from the product of a constant, arteriolar diameter, and red blood cell velocity, which were measured in the submucosal microcirculation. Isotonic glucose solutions (293 +/- 2 mosmol/kg) were prepared by diluting 5, 10, or 20 ml of 5% glucose, which is isotonic with plasma, to 100 ml with Ringer-bicarbonate buffer to concentrations of 250, 500, and 1,000 mg/100 ml. Glucose was added directly to Ringer-bicarbonate buffer to increase osmolality. The osmolalities of the 250, 500, and 1,000 mg/100 ml hypertonic solutions were 305 +/- 3,319 +/- 3, and 353 +/- 1 mosmol/kg, respectively. Glucose caused a concentration-related increase in estimated submucosal arteriolar blood flow that averaged 18-21% (n = 14), 24-27% (n = 14), and 34-45% (n = 14) at 250, 500, and 1,000 mg/100 ml glucose, respectively. There was no effect of solution osmolality on either the time course or the magnitude of the hyperemia at a given glucose concentration. Whereas the magnitude of the glucose-induced hyperemia averaged less than 50%, the application of 10(-2) M adenosine caused a fivefold increase in calculated blood flow (492 +/- 67%, n = 24). Thus, glucose caused relatively small increases in intestinal blood flow. If changes in luminal osmolality caused changes in intestinal tissue osmolality, then it is unlikely that hyperosmolality participates in the functional hyperemia associated with glucose absorption.
Muscarinic inhibition of canine small intestinal motility in vivo
Authors: Fox J. E. , Daniel E. E. , Jury J. , Robotham H.
Published: December 2017

The quiescent canine gastrointestinal tract responsed to close intraarterial acetylcholine with an atropine-sensitive, hexamethonium, and tetrodotoxin-insensitive contraction, thus suggesting acetylcholine interacts with a muscarinic receptor located on the muscle. When the gut is actively contracting (spontaneously, in response to field stimulation or to motilin), acetylcholine caused a contraction followed by prolonged inhibition of contractions. No such inhibition was apparent after tetrodotoxin; therefore, the receptor for acetylcholine-induced inhibition was apparently on nerves. Neither the acetylcholine-induced excitation nor the inhibition was altered by hexamethonium or reserpine treatment. Both inhibitory and excitatory responses were greatly reduced by atropine, suggesting that both receptors were muscarinic in nature. McNeil A343 produced inhibition but no excitation. Tetrodotoxin, hexamethonium, reserpine, and pirenzepine all increased the concentration of McNeil A343 required for production of 50% inhibition, suggesting it acts via multiple mechanisms. Furthermore, pirenzepine reduced both the inhibitory and excitatory response to acetylcholine, suggesting that it is nonselective in its action on the neural inhibitory or muscular excitatory receptors. We suggest that the presynaptic muscarinic receptor responsible for inhibitory effects of acetylcholine is on the postganglionic cholinergic neuron itself and constitutes an important negative-feedback loop to reduce excessive cholinergic output. Although such a mechanism has been found in vitro previously, this is the first report in vivo in canine small intestine.
Transport of thyroxine bound to human prealbumin into rat liver
Authors: Pardridge W. M. , Premachandra B. N. , Fierer G.
Published: December 2017

The transport into rat liver of thyroxine (T4) bound to human prealbumin was studied with the use of sera obtained from patients with thyroid hormone-binding globulin (TBG) deficiency and with purified human prealbumin. The unidirectional extraction of 125I-T4 by liver was measured after rapid injection of isotope mixed in human serum into the portal vein of ketamine-anesthetized rats. The percentage of total serum T4 transported into liver was 47.6 +/- 5.2% in subjects with TBG deficiency, and this represented a 50% increase in hepatic T4 transport relative to control human serum. Since T4 is bound to albumin and to prealbumin in complete TBG deficiency, these results suggested that T4 bound to human prealbumin was transported into rat liver. This was confirmed using portal vein injections of human prealbumin at physiological concentrations (0.1-0.3 mg/ml). At these concentrations, T4 bound to human prealbumin was readily transported into liver. These studies suggest factors present in the liver microcirculation inhibit the binding of T4 to human prealbumin such that T4 bound to human prealbumin is highly transportable in liver; conversely, T4 bound to rat prealbumin is not transportable in rat liver. The inability of human prealbumin to sequester T4 in plasma may provide the basis for the selective advantage in humans of TBG, which does sequester T4 in plasma.
Cholecystokinin potently releases somatostatin from canine fundic mucosal cells in short-term culture
Authors: Soll A. H. , Amirian D. A. , Park J. , Elashoff J. D. , Yamada T.
Published: December 2017

Previous studies indicated that gastrin-17 (G-17) and the octapeptide of colecystokinin (CCK-8) were equally potent in their interaction with receptors for 125I-[Leu15]G-17 on isolated canine parietal cells. These findings were inconsistent with the poor efficacy of CCK-8 compared with G-17 as stimuli of acid secretion in dogs. The present study examines the effects of G-17 and CCK-8 on the release of somatostatinlike immunoreactivity (SLI) from a fraction of small canine fundic mucosal cells separated by elutriation and placed in short-term culture. CCK-8 was considerably more potent and more effective than G-17 as a stimulant of SLI release from these cultured cells. CCK-8 was slightly more potent than G-17 in inhibiting 125I-[Leu15]G-17 binding to receptors in the same elutriator fraction. Our present findings support the hypothesis that the poor efficacy of CCK compared with G-17 as a stimulant of acid secretion may reflect pronounced activation of somatostatin-mediated acid-inhibitory mechanisms by CCK-8. The present data indicate that differences in affinity between CCK-8 and G-17 at the 125I[Leu15]G-17 receptor probably do not account for the greater efficacy of CCK-8; the receptor or cell activation mechanisms underlying this greater efficacy of CCK-8 on SLI release remain to be elucidated.
Androgens and estrogens affect hepatic bile acid sulfotransferase in male rats
Authors: Kirkpatrick R. B. , Wildermann N. M. , Killenberg P. G.
Published: December 2017

The effect of estrogens and androgens on hepatic glycolithocholate sulfotransferase activity was studied in male rats. Significant increases in specific activity were noted following treatment of rats for 21 days with 17 beta-estradiol, 17 alpha-ethynylestradiol, and the nonsteroidal estrogen agonists nafoxidine, tamoxifen, and diethylstilbestrol. Similar treatment of male rats with 5 alpha-dihydrotestosterone, hydrocortisone, norethindrone, and prolactin did not affect activity. To further assess the effect of androgens, male rats were castrated. Glycolithocholate sulfotransferase activity increased fivefold by 14 days after castration. Treatment of castrated rats with 5 alpha-dihydrotestosterone prevented the increase and maintained activity at the level of sham-operated animals. Castrated animals exhibited an additional increment in activity following treatment with 17 alpha-ethynylestradiol: specific activity in these animals rose to levels comparable with those measured in untreated female rats. These data suggest endogenous androgens maximally suppress hepatic glycolithocholate sulfotransferase activity in male rats. The data also indicate that activity is stimulated by estrogenic compounds of varied chemical structure and that stimulation is not solely due to suppression of androgen release by the testes as a consequence of estrogen treatment.
Gut hormones in stimulation of gastroduodenal alkaline secretion in conscious dogs
Authors: Konturek S. J. , Bilski J. , Tasler J. , Laskiewicz J.
Published: December 2017

Alkaline secretion from the fundic and antral pouches of the stomach and the loops of proximal and distal duodenum was measured in conscious dogs under basal conditions and after intragastric instillation of HCl solution, meat feeding, or intravenous infusion of various gut hormones. In control tests on fasted dogs HCO-3 output from the duodenal mucosa was severalfold higher than that from the gastric mucosa. Instillation of 10 mM HCl into the stomach resulted in a significant increment in HCO-3 secretion from the gastric pouches and proximal duodenal loops, and this was accompanied by a marked increase in plasma secretin, cholecystokinin (CCK), and pancreatic polypeptide (PP) levels. Meat feeding stimulated HCO-3 secretion from proximal duodenum, and it was accompanied by a significant elevation in plasma gastrin, secretin, CCK, gastric inhibitory peptide, and PP. Among exogenous hormones, the most effective stimulant of HCO-3 secretion was PP, which caused a significant increase in HCO-3 output from the gastric and duodenal mucosa at doses (125-500 pmol X kg-1 X h-1) that raised plasma PP to postprandial levels. CCK in physiological doses (21-85 pmol.kg-.h-1) also stimulated HCO-3 secretion from gastric pouches and proximal duodenal loops. Neurotensin stimulated HCO-3 secretion from both gastric pouches and duodenal loops. In contrast, gastrin or secretin did not affect significantly HCO-3 secretion from the gastroduodenal mucosa. This study provides evidence that some gut hormones, particularly PP, CCK, and neurotensin, may be involved in the physiological stimulation of gastroduodenal alkaline secretion.
Hepatic transport and binding of rose bengal in the presence of albumin and gamma globulin
Authors: Forker E. L. , Luxon B. A. , Sharma V. S.
Published: December 2017

Gamma globulin and albumin are compared with respect to their effects on the hepatic transport of rose bengal and with respect to the rates and affinities with which they bind this dye. The apparent intrinsic clearance of rose bengal is greater in the presence of albumin than in the presence of gamma globulin, and this difference increases with the protein concentration. Because the binding affinities of these proteins also differ, however, it cannot be concluded decisively that the mechanisms of dye removal are distinct. For both proteins the binding reaction rates as measured by stopped-flow spectrophotometry are much faster than the rate of convection along the sinusoid or the rate of removal of free dye by liver cells. The transport data and the binding rate constants are the basis for an extended theoretical model developed and analyzed in an accompanying report.
Intestinal absorption of 1,25-dihydroxyvitamin D3 in the rat
Authors: Sitrin M. D. , Pollack K. L. , Bolt M. J.
Published: December 2017

Intestinal absorption of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] from in vivo jejunal sacs was studied in rats with thoracic duct and bile duct cannulas. In 6 h 86.5% of the administered 1,25(OH)2D3 was absorbed, but only 7.3% was recovered in thoracic duct lymph. Appearance in plasma of [3H]-1,25(OH)2D3 after intrajejunal administration was identical in rats with and without diverting lymph cannulas, indicating that the 1,25(OH)2D3 is absorbed almost entirely via portal blood. When 1,25(OH)2D3 was instilled into the jejunum in a fat suspension without bile salts rather than a mixed micellar solution, less was recovered in lymph, but total intestinal absorption was unchanged. High-pressure liquid chromatography of a lymph extract demonstrated that 1,25(OH)2D3 was present only as the unchanged secosteroid. In lymph, only 4.1% of the 1,25(OH)2D3 was in the chylomicrons, with the remainder bound to the plasma protein fraction of lymph. Treatment of rats with cycloheximide to block chylomicron synthesis did not decrease absorption of 1,25(OH)2D3. These results indicate that intestinal absorption of 1,25(OH)2D3 is effective and not very dependent on luminal bile salts. Almost all 1,25(OH)2D3 is released from the intestine directly into portal blood and does not require packaging in chylomicrons for transport into intestine lymph.
Effects of proglumide on ductal and basolateral secretion of pancreatic digestive enzymes
Authors: Niederau C. , Grendell J. H. , Rothman S. S.
Published: December 2017

Previous studies have shown that proglumide acts as a cholecystokinin (CCK) receptor antagonist in isolated pancreatic acini. To establish the effect of proglumide in the intact organ, its effects on both CCK-stimulated ductal and basolateral secretion of digestive enzymes were studied in the in vitro rabbit pancreas. CCK-stimulated ductal secretion of chymotrypsinogen, amylase, and total protein, as well as basolateral secretion of amylase, was inhibited by proglumide in a dose-dependent manner. Regression lines comparing ductal chymotrypsinogen and amylase outputs also were altered significantly by proglumide in a dose-dependent manner, with amylase secretion inhibited to a lesser degree. Similarly, the relative rates of amylase secretion across the ductal versus the basolateral cell surface were altered, with basolateral secretion inhibited to a lesser degree. The effects seen with increasing concentrations of proglumide at a given concentration of CCK mirrored the effects seen with decreasing the concentration of CCK in the absence of proglumide. Proglumide did not affect ductal or basolateral secretion stimulated by a cholinergic agonist and did not affect unstimulated pancreatic secretion. Thus, proglumide appears to act as a selective antagonist of CCK-stimulated secretion in the intact organ. The results further indicate that interactions of an agonist and an antagonist at the CCK receptor can alter not only the overall amount of enzymes secreted but their relative proportions as well.
Localization of sites within dorsal motor nucleus of vagus that affect gastric motility
Authors: Pagani F. D. , Norman W. P. , Kasbekar D. K. , Gillis R. A.
Published: December 2017

The purpose of our study was to determine the localization of sites within the dorsal motor nucleus of the vagus (DMV) of the cat that when stimulated would increase gastric motility. To do this, two types of experiments were performed. First, the retrograde tracer fast blue was injected into the antrum and pylorus, and labeled neurons in the DMV were identified. Second, electrical stimulation was performed in areas of the DMV labeled with fast blue as well as in nearby areas with no labeling while monitoring gastric motility, arterial pressure, and heart rate. Results from the first type of studies revealed that peak labeling in the DMV occurred between 0.56 and 1.56 mm rostral to obex. Electrical stimulation in this area using 100 microA, 0.2 ms duration pulses, and 50 Hz resulted in increases in antral and pyloric contractions in 20 animals. The magnitude of pyloric and antral responses elicited by stimulation of the DMV generally correlated to the number of cell bodies labeled with fast blue within the DMV. No changes in arterial pressure occurred, and only a slight (-4%) decrease in heart rate was observed. Maximal increases in motility occurred with 20 Hz (antrum) or 100 Hz (pylorus). These increases in motility were maintained even at 200- and 400-Hz stimulation. Ipsilateral vagotomy or pretreatment with propantheline bromide prevented the increases in gastric motility produced by electrical stimulation of the DMV. Electrical stimulation of more rostral sites in the DMV, the medial nucleus of the solitary tract (NTS), and an area within 1.0 mm medial to the DMV resulted in attenuated or no motility responses. Stimulation of the medial nucleus of the NTS did result in pronounced slowing in heart rate (-61 +/- 21 beats/min). These results suggest that there is a localization of a “stomach area” within the DMV and that electrical stimulation of this area results in gastric motility responses that are mediated by vagal fibers projecting directly to the stomach. In addition, electrical stimulation of the DMV results in selective effects on the gastrointestinal tract in that no pronounced changes in heart rate and arterial pressure occur.
Development of gastrointestinal mucosal barrier. VII. In utero maturation of microvillus surface by cortisone
Authors: Pang K. Y. , Newman A. P. , Udall J. N. , Walker W. A.
Published: December 2017

When studying mucosal barrier function of developing animals, we noted that intestinal microvillus membranes (MVM) of newborn animals differ in their fluidity and binding characteristics to lectins compared with adult MVM. To further investigate these differences and determine whether maturation of the microvillus surface could be accelerated in utero, pregnant rats were given intraperitoneal cortisone beginning on the 17th day of gestation. Control and cortisone-treated animals were allowed to deliver normally, and the small intestines from newborns were used to isolate MVM. Microvillus membrane surface characteristics were evaluated by employing an 125I-labeled fucose-specific lectin, Ulex europeus (UEA). Changes in MVM proteins were monitored by disaccharidase activities and sodium dodecyl sulfate-polyacrylamide electrophoresis. MVM fluidity was accessed using a 5-doxyl stearic acid label and electron-spin-resonance spectroscopy. Results from these studies indicate that the birth weights of newborn rats exposed to cortisone in utero were significantly reduced; sucrase activity was prematurely induced and specific activities of lactase and maltase were enhanced in the intestines of the cortisone-treated newborns as contrasted with control animals. Furthermore, binding of 125I-UEA to MVM was greatly increased in treated animals. MVM fluidity decreased (P less than 0.001) compared with control animals and resembled the structural characteristics of more mature MVM. These results suggest that cortisone exposure in utero accelerate maturation of the microvillus surface of enterocytes.
Role of small intestine in pathogenesis of hyperlipidemia in diabetic rats
Authors: Popper D. A. , Shiau Y. F. , Reed M.
Published: December 2017

The small intestine can utilize endogenous substrates for triglyceride synthesis. In diabetes mellitus, potential endogenous substrates are elevated. This study was designed to investigate whether intestinal triglyceride production utilizing endogenous substrates contributes to the pathogenesis of hyperlipidemia in diabetes. Intestinal fatty acid esterification as well as activities of acyl-CoA synthetase and acyl-CoA monoglyceride acyltransferase are the same in diabetic and control rats when the results are expressed per milligram protein. However, due to marked intestinal hypertrophy these activities are increased when the results are expressed as per centimeter gut length. In the mesenteric lymph fistula rat model, we found that during fasting diabetic rats have a greater than twofold increase in triglyceride output that is carried mainly by very low-density lipoproteins (VLDL). During lipid infusion, total triglyceride fatty acid output was not different between diabetic and control rats, although there were significant differences in the patterns of partition of endogenous and exogenous triglyceride into chylomicrons and VLDL. Endogenous triglyceride production did not increase in diabetic rats during lipid infusion. In contrast, there was a substantial increase in endogenous triglyceride production in the control group to a level comparable with that of the diabetic rats. There was a significant reduction in incorporation of exogenous triglyceride into chylomicrons in diabetic rats.
Postprandial regulation of intestinal blood flow: role of gastrointestinal hormones
Authors: Premen A. J. , Kvietys P. R. , Granger D. N.
Published: December 2017

Systemic arterial pressure, jejunal perfusion pressure, and jejunal blood flow were measured in eight autoperfused canine jejunum preparations (5 dogs) before and during local intra-arterial infusion of physiological doses of secretin (18.5 pM), neurotensin (233 pM), and cholecystokinin octapeptide (CCK-8, 30 pM). Intra-arterial infusion of secretin, neurotensin, or CCK-8 alone did not affect either systemic or jejunal arterial pressures. Likewise, jejunal blood flow was not significantly altered by secretin (3 +/- 3%), neurotensin (-5 +/- 4%), or CCK-8 (-5 +/- 5%). Even when all three hormones were infused simultaneously, jejunal blood flow was not altered (2 +/- 3%). However, when infused at rates that produced calculated arterial blood levels some 100 times greater than those reported as “postprandial,” each hormone alone, as well as in combination, produced marked increases in jejunal blood flow. Secretin, neurotensin, and CCK-8 increased blood flow by 34 +/- 8, 31 +/- 11, and 24 +/- 5%, respectively. Simultaneous infusion of all three hormones increased jejunal blood flow by 47 +/- 11%. These data suggest that, either alone or in combination, secretin, neurotensin, and CCK-8 are not of quantitative importance in regulating jejunal blood flow during the postprandial state. However, higher (presumably pharmacological) blood levels of these hormones do significantly elevate jejunal blood flow.
Effect of proglumide on rat pancreatic growth
Authors: Yamaguchi T. , Tabata K. , Johnson L. R.
Published: December 2017

Proglumide, a glutaramic acid derivative, is a specific competitive inhibitor of gastrin and cholecystokinin (CCK) receptors. As such, it blocks gastrin-stimulated acid secretion, the trophic effect of gastrin, and CCK-stimulated smooth muscle contraction and acinar cell secretion. In the current study we have demonstrated that proglumide (100 mg/kg three times per day) blocks the trophic effect of a low dose of CCK octapeptide (300 ng/kg) given three times a day for 2 days. The same dose of proglumide when given alone for 6 days, however, resulted in a significant stimulation of pancreatic growth. Proglumide had no effect on the trophic response to a high dose of CCK-OP (5 micrograms/kg) administered for either 2 or 6 days. These results indicate that given over a period of several days proglumide behaves like a partial agonist of pancreatic growth.
Vasoactive agents and the mesenteric microcirculation
Authors: Harper S. L. , Bohlen H. G. , Granger D. N.
Published: December 2017

Vasoactive agents are known to have a variety of effects on the dynamics of the mesenteric microcirculation. We compare and contrast the effects of both vasodilators and vasoconstrictors on capillary filtration coefficient, vascular permeability, tissue oxygen tension, and microvascular pressure. The various methodologies used to determine the above quantities are discussed, as well as the limitations and advantages of each approach. Discrepancies between the results obtained with particular classes of vasoactive agents are discussed relative to both dosage and route of administration. In addition, data obtained for each parameter using both whole-organ and in vivo microscopic techniques are reconciled relative to the characteristics of each approach. Experimental designs are proposed that may help minimize future inconsistencies in the data, as well as maximize the relative advantages of available techniques.
Systemic and splanchnic hemodynamic disturbances in conscious rats with experimental liver cirrhosis without ascites
Authors: Fernandez-Munoz D. , Caramelo C. , Santos J. C. , Blanchart A. , Hernando L. , Lopez-Novoa J. M.
Published: December 2017

Rats with CCl4-induced cirrhosis of the liver show histological and clinical features that closely resemble those of the disease in humans. Metabolic cages were used and hemodynamic studies (15-micrograms radioactive microspheres) were performed on 10 conscious, nonascitic, cirrhotic rats and in 10 control rats. Compared with control animals, cirrhotic rats showed lower sodium excretion (0.80 +/- 0.07 vs. 1.01 +/- 0.07 meq/day), total solute excretion (12.52 +/- 0.79 vs. 19.38 +/- 3.7 mosmol/day), and increased aldosterone excretion. No differences were observed in urinary epinephrine and norepinephrine excretion. Cirrhotic rats showed also slight hypotension, increased cardiac output (48.97 +/- 3.94 vs. 26.97 +/- 2.3 ml X min-1 X 100 g-1) without tachycardia, and decreased total peripheral resistance, which was mainly attributed to reduced renal and skeletal muscle resistances with increased blood flow throughout these areas. Cirrhotic rats showed increased hepatic vascular resistances by both portal and arterial inputs with portal hypertension (16.15 +/- 1.01 vs. 9.60 +/- 0.77 cmH2O) but without differences in total hepatic blood flow or portal-systemic shunt rate with respect to control rats. Plasma renin content was not significantly different between the groups of rats. From these data it can be concluded that nonascitic, cirrhotic rats show a hyperdynamic circulatory state, which seems to be caused by a peripheral vasodilation of unknown mechanism; portal-systemic shunting does not seem to be a necessary condition for the hyperdynamic status at this early stage of the hemodynamic disturbances.
Role of H+ transport in ursodeoxycholate-induced biliary HCO-3 secretion in the rat
Authors: Garcia-Marin J. J. , Corbic M. , Dumont M. , de Couet G. , Erlinger S.
Published: December 2017

Biliary bicarbonate secretion may occur by transport of bicarbonate itself or of H+ (or OH-). To distinguish between these two mechanisms, we have studied the effects of bicarbonate deprivation or substitution by weak acids in the perfusate of isolated rat livers on ursodeoxycholate-induced bicarbonate secretion. Livers were perfused with an erythrocyte-free solution containing either the impermeant buffer Tricine (25 mM) or 25 mM Tricine and 13 mM bicarbonate, acetate, or 5,5-dimethyloxazolidine-2,4-dione (DMO), and ursodeoxycholate was infused. Tauroursodeoxycholate, which does not stimulate bicarbonate secretion, served as a control. During ursodeoxycholate infusion 1) the increase in bile flow, in microliter X min-1 X g liver-1 (+/- SE), was significantly higher in livers perfused with Tricine and bicarbonate (1.29 +/- 0.06), Tricine and acetate (1.46 +/- 0.07), and Tricine and DMO (1.30 +/- 0.04) than in livers perfused with Tricine alone (0.99 +/- 0.04); and 2) biliary bicarbonate, acetate, or DMO concentrations and bile pH were significantly higher than the corresponding perfusate values. In contrast, during tauroursodeoxycholate infusion bile flow was the same whatever the perfusate, and bile pH was lower than pH of the perfusate. Therefore, ursodeoxycholate-induced choleresis and bile alkalinization do not depend on bicarbonate as such (which can be replaced by acetate or DMO). This suggests that ursodeoxycholate-induced biliary bicarbonate secretion is the result of H+ (or OH-) transport rather than transport of bicarbonate itself.
Relation between free cytosolic calcium and amylase release by pancreatic acini
Authors: Ochs D. L. , Korenbrot J. I. , Williams J. A.
Published: December 2017

Pancreatic acini were loaded with the Ca-selective fluorescent indicator quin-2 by incubation with its acetyoxymethyl ester. Loading acini with 844 +/- 133 microM quin-2 altered neither their ultrastructure nor their viability. The rate of amylase release from quin-2-loaded acini in response to the secretagogue carbachol, however, was significantly smaller than that of control acini. Studies in which acini were loaded with both quin-2 and a similar Ca-chelating compound, BAPTA, indicated that this reduced amylase release was related to the Ca buffering properties of quin-2. The concentration of free intracellular Ca calculated from the fluorescence of quin-2 was 90 +/- 18 nM. Stimulation by carbachol of acini suspended in media containing 1.25 mM Ca caused a rapid, transient enhancement of this value. After stimulation amylase release, the onset of the rise in free cytosolic Ca levels was observed in 1.1 +/- 0.1 s following the addition of agonist, and peak Ca levels (545 +/- 112 nM) were obtained within 5.3 +/- 0.3 s. For concentrations of carbachol less than or equal to 10(-6) M, a stoichiometric relation was found between stimulated amylase release and the peak concentration of free cytosolic Ca achieved. At higher concentrations of carbachol, however, the peak free cytosolic Ca remained constant while amylase release declined. The latency of the rise in intracellular Ca following stimulation of acini suspended in Ca-free media was not different from that observed for acini suspended in normal media, but the rise time was significantly prolonged. In the presence of extracellular Ca, the intracellular level of Ca remained elevated 2.8-fold above basal levels for at least 15 min following stimulation with 10(-6) M carbachol, whereas it had returned to near resting levels by 15 min when either 3 X 10(-7) or 3 X 10(-5) M carbachol was the stimulus. The Ca ionophore ionomycin (10–6 M) induced changes in the level of free cytosolic Ca similar to those caused by 10(-6) M carbachol. Ionomycin, however, stimulated only approximately one-third as much amylase release. These data suggest that factors in addition to changes in free cytosolic Ca may be important in regulating enzyme secretion by pancreatic acinar cells.
Dietary fat assimilation and bile salt absorption in the killifish intestine
Authors: Honkanen R. E. , Rigler M. W. , Patton J. S.
Published: December 2017

Radiolabeled taurocholate (TC) and triolein were used to study fat assimilation and bile salt absorption in the stomachless saltwater killifish, Fundulus heteroclitus. Fat absorption occurred primarily in the proximal intestine with approximately 87% of a single dose (9 mg fat/8 g fish) absorbed in 2 h. Luminal triolein hydrolysis and enterocyte triolein resynthesis were tightly coupled. Killifish gallbladder bile contains taurocholate and cholate in an equal molar ratio at a combined concentration of 237 +/- 25 mM (n = 10) in 24-h-fasted fish. During fat assimilation luminal bile salt and fatty acid concentrations ranged between 10 and 30 mM. Between and during meals the total concentration of bile salts in the intestinal tissue remained roughly constant (4–6 mM) with the proximal one-third of the intestine containing 40% of the total and the remainder equally distributed between the mid and distal regions. All three regions of the intestine rapidly incorporated ingested TC in vivo, with the amount incorporated proportional to the pool size. In contrast, in vitro at low TC concentrations (60 nM), the distal one-third of the intestine incorporated 10 times as much TC in 2-min uptake experiments as the proximal and mid regions. Although there are many similarities between fat and bile salt assimilation in killifish and mammals, overall the processes are much simpler in killifish.
Action of pancreatic polypeptide on rat pancreatic secretion: in vivo and in vitro
Authors: Louie D. S. , Williams J. A. , Owyang C.
Published: December 2017

The biological activity of bovine pancreatic polypeptide (BPP) on rat exocrine pancreatic secretion was compared in vivo and in vitro. In anesthetized rats prepared with a bile-pancreatic duct cannula, BPP inhibited cholecystokinin (CCK)-stimulated (10 IDU . kg-1 X h-1) protein secretion in a dose-related manner (P less than 0.001). CCK, from 5-20 IDU . kg-1 X h-1, did not alter the degree of inhibition by BPP at 40 micrograms . kg-1 X h-1, suggesting a nonsurmountable inhibition. Analogues of BPP, including rat pancreatic polypeptide, neuropeptide Y, peptide YY, and the C-terminal hexapeptide of PP, also inhibited CCK-stimulated protein secretion. To determine whether BPP acts directly on acinar cells to suppress enzyme secretion, in vitro studies were performed. BPP and its analogues did not suppress octapeptide of CCK (CCK-8)-stimulated amylase release from either isolated rat pancreatic acini or preparations of pancreatic lobules. Specific binding of 125I-BPP to pancreatic acini was also not observed. From our data we conclude that BPP acts to inhibit pancreatic enzyme secretion in the rat in a noncompetitive manner. Absence of an effect by BPP or its analogues in vitro coupled with an absence of 125I-BPP binding to acini suggest that the inhibitory action of PP on exocrine pancreatic function is mediated by indirect mechanisms.
Gastric mucosal blood flow measured by laser-Doppler velocimetry
Authors: Kiel J. W. , Riedel G. L. , DiResta G. R. , Shepherd A. P.
Published: December 2017

To determine the feasibility of measuring gastric mucosal blood flow by laser-Doppler velocimetry (LDV), we utilized two LDV flowmeters to monitor blood flow in mucosa and serosa of chambered canine stomach. In isolated, nonautoregulating gastric segments vasodilated with isoproterenol, LDV mucosal and muscularis blood flows were both linearly related to total electromagnetic blood flow during step increases in perfusion pressure. To assess the depth of the LDV measurement, we recorded reactive hyperemia following arterial occlusion. Reactive hyperemia was frequently registered in the mucosa but rarely in muscularis. Placing a layer of nonperfused mucosa-submucosa between the probe and the perfused mucosa abolished the resting LDV mucosal flow signal and attenuated the recording of peak hyperemia by 85%. Furthermore, intra-arterial infusions of both adenosine and isoproterenol frequently increased LDV mucosal flow and decreased LDV muscularis flow, although total flow was consistently increased. These findings indicate that our LDV instruments yield linear, superficial measurements of gastric blood flow in either mucosa or muscularis. Although calibration in absolute units remains to be achieved, our results demonstrate that LDV is a practical means of studying the gastric mucosal microcirculation.
Effect of starvation on amino acid and peptide transport and peptide hydrolysis in humans
Authors: Vazquez J. A. , Morse E. L. , Adibi S. A.
Published: December 2017

Jejunal disappearance rates of glycine (a model for neutral amino acid absorption), triglycine (a model for peptide transport), and tetraglycine (a model for brush-border membrane hydrolysis) were investigated by an in situ perfusion technique before and after 2 wk of starvation in seven obese volunteers. The three test solutions of glycine, triglycine, and tetraglycine were equivalent in glycine content. Before starvation glycine absorption was greatest from the triglycine solution and smallest from the glycine solution. Starvation significantly decreased glycine absorption from both glycine and triglycine solutions, but not from the tetraglycine solution. However, glycine absorption was still significantly greater from the triglycine and tetraglycine solutions than from the glycine solution. Starvation had no significant effect on the disappearance rate of triglycine, but it increased the disappearance rate of tetraglycine. We conclude that a) starvation has different effects on functions of mucosal brush-border membrane, for example, it reduces amino acid absorption but enhances peptide hydrolysis; and b) the greater amino acid absorption from peptides is maintained even after 2 wk of starvation, suggesting that peptides are superior to free amino acids as the nitrogen source for enteral nutrition if employed in malnutrition.
Capillary orientation of rat pancreatic D-cell processes: evidence for endocrine release of somatostatin
Authors: Aponte G. , Gross D. , Yamada T.
Published: December 2017

We examined the ultrastructure of somatostatin-containing pancreatic D-cells in the rat in order to shed light on the function and mode of action of somatostatin in the pancreas. D-cells were first identified by indirect immunocytochemistry with the peroxidase-antiperoxidase technique on semithin (1-micron) sections of 2% glutaraldehyde-1.7% paraformaldehyde-fixed tissue from the tail of the pancreas. Fine ultrastructure of the positively identified D-cells was examined in adjacent sections (0.08 micron) by electron microscopy. D-cells characteristically exhibited long cytoplasmic projections that extended to capillaries. Each cell was divided arbitrarily into three zones of roughly equal size, nuclear, central, and capillary, and distribution of secretory granules into each zone was quantified. In unstimulated cells, secretory granules were dispersed throughout the D-cell. In sections obtained from rats stimulated to secrete somatostatin by infusion of 20 mM glucose-5 mM theophylline-20 mM L-arginine HCl, 75 +/- 4% of the D-cell granules was polarized to the capillary end of the cell, while only 54 +/- 2% was is this region in unstimulated rats (P less than 0.05). These studies suggest that pancreatic somatostatin is released into islet capillaries.
Effects of cations on pH gradient-stimulated sulfate transport in rabbit ileal brush-border membrane vesicles
Authors: Schron C. M. , Knickelbein R. G. , Aronson P. S. , Della Puca J. , Dobbins J. W.
Published: December 2017

In brush-border membrane vesicles from rabbit ileum, we previously reported pH gradient-stimulated SO4 uptake and presented evidence that this represents carrier-mediated SO4-OH exchange. In the present study inhibitors of SO4-OH exchange (H-SO4 cotransport) were shown not to inhibit Na-SO4 cotransport, suggesting that these are two separate carrier-mediated transport mechanisms. While pH gradient-stimulated SO4 uptake was inhibited 87% by 0.1 mM 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, disodium salt (DIDS) and 79% by 1.0 mM furosemide, Na+-stimulated SO4 uptake was only inhibited 11 and 0%, respectively. K+ (20 mM), Cl (5 mM), and oxalate (0.25 mM) inhibited pH gradient-stimulated SO4 uptake (38-65%) but had no effect on Na+-stimulated SO4 uptake. Finally, at Na+ concentrations (10 mM) significantly less than that required for Na+-stimulated SO4 uptake (60-100 mM), external Na+ inhibited pH gradient-stimulated SO4 uptake, suggesting two independent effects of this cation. SO4 uptake was also inhibited by external K+ both in the presence and absence of a pH gradient. A Dixon plot of the DIDS-sensitive SO4 uptake under pH gradient conditions yielded a straight line, indicating a single site of interaction between external K+ and the SO4-OH carrier (apparent Ki = 7.2 mM). In contrast to the inhibition by external K+, internal K+ stimulated SO4 uptake. This effect was DIDS sensitive and not enhanced by valinomycin, suggesting an interaction of internal K+ with the SO4-OH exchanger independent of a K+-induced electrical potential. SO4 uptake and the effects of K+ were pH modulated with less SO4 uptake and less K+ effect at higher pH.(ABSTRACT TRUNCATED AT 250 WORDS)
Factors influencing triacylglycerol delivery into mesenteric lymph
Authors: Mansbach C. M. , Arnold A. , Cox M. A.
Published: December 2017

The transport of triacylglycerol (TG) in mesenteric lymph was studied in rats with duodenal and mesenteric lymphatic cannulas with or without bile fistulas. Rats were infused with 135 mumol glycerol trioleate (TO) for 4 h, followed by 5 h of NaCl infusion. Rats with intact fistulas prefed 20% corn oil had nearly twice the maximum output of TG in lymph as controls. Decay from peak values was zero order for controls and indeterminate for rats prefed corn oil. In rats with bile fistulas, less TG was transported in lymph than in those in which 2 mM phosphatidylcholine (PC) was added to the infusate. The decay from maximum values was zero order for controls and first order for rats infused with PC and TO. Recovery of infused [3H]glycerol trioleate in controls was 43% and increased to 68% on inclusion of PC in the infusate. We conclude that in chow-fed rats lymph TG delivery rates were well below infusion rates, suggesting alternate TG transport routes, TG transport was improved by supplementing the infusate with PC or prefeeding with 20% TG in chow, and PC may be limiting in TG transport in rats with bile fistulas.
Interaction between stimuli and their antagonists on frog esophageal peptic glands
Authors: Shirakawa T. , Hirschowitz B. I.
Published: December 2017

The peptic glands, which are located in the mucosa of the distal esophagus in the frog, respond to multiple stimuli. In vitro studies were performed, using mucosal sheets of the esophagus of Rana catesbeiana, during the summer months when the glands are fully responsive to determine whether the receptors for the stimuli [cholinergic, beta-adrenergic, and peptidergic (bombesin but not cholecystokinin)] are specific to the stimuli. Through the use of three classes of antagonist, we found that 1) atropine defined the muscarinic nature of the bethanechol stimulation, 2) propranolol defined the beta-adrenergic nature of stimulation by isoproterenol, and 3) the substance P analogue [D-Arg1,D-Pro2,D-Trp7,9,Leu11]substance P was specific for the peptide bombesin. No cross-inhibition was seen, and dibutyryl cGMP did not inhibit any of the three stimuli. Moreover, any two of the three stimuli in combination stimulated more pepsinogen than either alone but the same as the sum of the two individual responses. Both lines of evidence indicate that there are at least three independent receptor pathways for stimulation of pepsinogen secretion in these glands.
Effect of atropine on digested food-induced intestinal hyperemia
Authors: Nyhof R. A. , Ingold-Wilcox D. , Chou C. C.
Published: December 2017

The aim of our study was to determine whether the discrepancy in the data reported on the effect of atropine on food-induced intestinal hyperemia results from a difference in experimental materials and methods. In the first two series of experiments, atropine (0.5 mg/kg iv) was given before or during intraluminal perfusion of digested food plus bile through a long jejunal loop (62% of the total small intestine) at 4 ml/min for 60 min while measuring the portion of the blood flow through the superior mesenteric artery (SMA) that perfused the loop. Atropine per se had no effect on jejunal blood flow. Before atropine food increased flow 31.5 +/- 10.1% and after atropine flow increased 54.8 +/- 11.0 and 66.0 +/- 28.0% above controls in the first and second series, respectively. Atropine also increased net fluid volume absorption. In the third series, food alone and food plus bile were placed into the lumens of the two adjacent jejunal segments. Atropine had no effect on the increases in flow and oxygen uptake produced by food alone but enhanced the hyperemia produced by food plus bile without affecting the increase in oxygen uptake. Our results suggest that the previously reported inhibition of increased SMA flow by atropine is due to the inhibitory effect of atropine on gastrointestinal motility and inhibition of pancreatic blood flow. In conclusion, food-induced jejunal hyperemia does not result from a direct vasodilator action of the cholinergic nerves.
Regulation of jejunal blood flow and oxygenation during glucose and oleic acid absorption
Authors: Chou C. C. , Nyhof R. A. , Kvietys P. R. , Sit S. P. , Gallavan R. H.
Published: December 2017

To differentiate the mechanisms whereby actively absorbed glucose and passively absorbed oleic acid increase blood flow and oxygen uptake during their absorption, the effects of these two nutrients on jejunal blood flow, arteriovenous oxygen difference [(a-v)O2], O2 uptake, absorption, rubidium extraction, and capillary permeability-surface area product (PS) were compared in anesthetized dogs. Oleic acid (37 mM) produced significantly greater hyperemia (+28.2%) than glucose (270 mM) did (+12.5%). As estimated by (a-v)O2, tissue oxygen extraction was decreased by oleic acid (-12%) but increased by glucose (+6.5%); the increases in O2 uptake by these two nutrients did not differ significantly. Glucose absorption was accompanied by an increase in rubidium extraction and capillary PS (+11.3%), whereas oleic acid absorption was not. Unlike glucose, intra-arterial infusion of oleic acid decreased vascular resistance and increased blood flow equally to the mucosa and muscularis layers. A significant relation existed between oleic acid absorption and blood flow but not between glucose absorption and blood flow. The enhancement of glucose-induced hyperemia by bile was not related to glucose absorption. Unmasking of oleic acid-induced hyperemia by bile is unrelated to oleic acid absorption but is related to solubility of oleic acid in aqueous solution. The above findings suggest that glucose absorption affects both resistance and exchange vessels, whereas oleic acid absorption affects primarily resistance vessels.
Emptying of saline meals by the cat stomach as a function of pyloric resistance
Authors: Schulze-Delrieu K. , Brown C. K.
Published: December 2017

The effect of the pylorus on the rate of gastric emptying and on the pattern of flow from the stomach to the duodenum was studied. Cat stomachs were filled with 50, 100, or 150 ml of 0.9 N saline, and intragastric pressure and gastric fluid output were monitored continuously. The tip of the collecting cannula was positioned either in the duodenum thus allowing the pylorus to close) or in the pyloric segment thus preventing the pylorus from interfering with gastric outflow). Initial experiments demonstrated that fluid output was similar for the cat stomach in situ and in vitro. Incremental output (i.e., the absolute volume emptied per collection period) increased with the meal size and was proportional to the fluid volume actually remaining in the stomach; fractional gastric output (i.e., the volume emptied as a percentage of the actual gastric volume) did not change with meal size. The half time for gastric emptying was greater with the collecting cannula positioned in the duodenum than in the pylorus (e.g., with the 100-ml meal, 154 vs. 46 s). With the cannula in the pylorus, gastric outflow was constant and ceased only when gastric emptying had terminated. With the cannula in the duodenum, outflow was pulsatile and ceased intermittently at gastric volumes that were subsequently emptied. We conclude that the cat pylorus renders the outlet of the stomach continent even to liquids; furthermore, the pylorus imparts a pulsatile pattern to flow of liquids from the stomach to the duodenum.