bluuebunny/crossref_metadata_2025 huggingface dataset:
Ventromedial hypothalamic lesions elevate basal and cephalic phase gastric acid output
Authors: Weingarten H. P. , Powley T. L.
Published: December 2017

With the use of a new technique for the measurement of gastric acid output in the rat, this study identifies ventromedial hypothalamic (VMH) lesion-induced changes in gastric acid secretion. Basal and cephalic phase gastric acid secretion were monitored in VMH- and sham-lesioned control rats on days 1, 5, 9, 13, and 17 postlesion as well as after the full development of obesity. VMH lesions resulted in increases of both phases of secretion. The magnitude of hypersecretion in lesioned rats developed with time and was fully developed by day 9 postlesion. The hypersecretion did not require a hyperphagia or weight gain, but its degree correlated with subsequent weight gain. These data, in conjunction with a review of VMH lesion effects on insulin secretion, suggest a widespread effect of VMH lesions on visceral secretory responses. The relevance of these data to the etiology of the VMH syndrome is discussed.
Effect of cholecystokinin-octapeptide on opossum lower esophageal sphincter
Authors: Dent J. , Dodds W. J. , Hogan W. J. , Arndorfer R. C. , Teeter B. C.
Published: December 2017

We evaluated the action of cholecystokini-octapeptide (CCK-OP) on lower esophageal sphincter (LES) pressure in the opossum. LES pressure was recorded by an infused sleeve device that straddled the sphincter, whereas intraluminal esophageal pressure and gastric pressure were recorded via conventional manometric catheters. Progressive intravenous pulse doses of CCK-OP caused 1) graded increases in LES pressure, 2) circular and longitudinal smooth muscle contraction in esophageal body, and 3) mild increases in intragastric pressure. Pressor effect of CCK-OP on the LES was weakly antagonized by tetrodotoxin (TTX), but not by atropine, phentolamine, or pyrilamine. TTX antagonism of CCK-OP appeared to be nonspecific because TTX also partially antagonized LES contractions induced by pentagastrin, substance P, and bethanechol. We conclude that CCK-OP at doses that cause LES relaxation in other species induces LES contraction in the opossum. This pressor effect appears to be elicited by a direct action of the hormone on LES smooth muscle.
Effect of parenteral nutrition on protein synthesis and liver fat metabolism in man
Authors: Stein T. P. , Buzby G. P. , Gertner M. H. , Hargrove W. C. , Leskiw M. J. , Mullen J. L.
Published: December 2017

We studied the effect of parenteral nutrition with amino acids and hypertonic glucose on protein synthesis and liver fat metabolism. Patients with operable gastrointestinal tract malignancies were divided into two groups. Group I ate the hospital diet ad libitum for the 7-10 days preceding surgery. Group II were given adjuvant parenteral nutrition (APN) for 7-10 days prior to the surgical removal of the tumor. Daily nutrient intake and nitrogen balance were determined. [15N[glycine (1-2 g) was infused at a constant rate for 12-18 prior to surgery. During surgery, blood, liver, and muscle specimens were taken for 15N analysis. Fractional protein synthesis rates were estimated by the method of Garlick et al. (Biochem. J. 136: 935-945, 1973). The fat content and distribution pattern in the liver was determined by gas chromatography-mass spectrometry. The following results were found. 1) APN increaed the albumin synthesis rate. 2) The fraction of linoleate in the total liver fatty acids were reduced by 75% in the APN patients. 3) Some of the APN patients developed fatty livers during the study. When the APN patients were subdivided on the basis of whether they had fatty livers, it was found that only those patients who did not accumulate fat showed an improvement in their plasma albumin concentration during the period of parenteral nutrition.
Fetal bile salt metabolism: placental transfer of taurocholate in sheep
Authors: Sewell R. B. , Hardy K. J. , Smallwood R. A. , Hoffman N. E.
Published: December 2017

Bidirectional placental transfer of taurocholate was studied in conscious, pregnant sheep near term. In studies of maternal-to-fetal transfer sodium, [14C]cholate was injected intravenously daily into the mother to label the endogenous cholate pool. Ninety-five percent of the radiolabel was present in the maternal pool as [14C]taurocholate. No radiolabel was detected in the fetal bile over 6-9 days, indicating minimal placental transfer of taurocholate to the fetus. In contrast, mean fetal-to-maternal transfer of taurocholate, studied over 3-4 days, was 2.6 mumol/24 h, representing approximately 2%/day of the fetal taurocholate pool. We conclude that in the sheep placental transfer from the mother, at term, contributes little if any taurocholate to the fetal pool. However, the placenta may be an important excretory organ for fetal bile salts, thus playing a key role in fetal steriol homeostasis.
Intestinal kinetic parameters: effects of unstirred layers and transport preparation
Authors: Thomson A. B. , Dietschy J. M.
Published: December 2017

Three in vitro tissue preparations were used to derive kinetic parameters for the transport of D-glucose in rabbit jejunum, and the resistance of the unstirred water layer was varied by altering the rate of stirring of the bulk phase. The apparent permeability coefficient (Pd*) of the rabbit jejunum for D-glucose was much higher from everted sacs and full-thickness biopsies than from intestinal discs. Failure to adjust the experimentally determined flux for the contribution of the passive component led to errors in the estimation of the maximal transport rate (Jdm) and in the apparent Michaelis constant (Km*). Jdm was higher in biopsies than everted sacs or discs, Km was also higher in biopsies. With each tissue preparation Km* and Pd* were markedly influenced by stirring the bulk phase, whereas Jdm was unchanged. The results indicate that failure to account for the effect of the passive component and the unstirred layer leads to major errors in the estimation of Km*, Pd*, and Jdm. Furthermore, the magnitude of these kinetic constants is influenced by the type of in vitro system used to derive the constants, and it is therefore invalid to extrapolate the results obtained using one preparation to those utilizing another preparation, or to the in vivo situation.
Hepatic artery response to vasopressin
Authors: Bynum T. E. , Fara J. W.
Published: December 2017

As vasopressin began to be used widely to control gastrointestinal hemorrhage, there was concern over the effect of vasopressin on the hepatic circulation. Although an initial vasoconstrictor effect of the drug has been described on the hepatic artery, a secondary increase in blood flow ensues. This increase has been attributed to the accompanying decrease in portal blood flow produced by vasopressin. The present study was done to investigate the mechanism of the response of hepatic artery to vasopressin in dogs. Anesthetized dogs were studied with flow probes placed on hepatic, superior mesenteric, femoral, and renal arteries, and the animals were prepared so that portal blood was diverted into jugular vein, with portal inflow to liver delivered at varying rates with blood pumped from a femoral artery. Vasopressin (0.5-1.0 U/kg) was administered intravenously. Results in dog indicate the biphasic response of hepatic artery blood flow to vasopressin is not dependent on changes in portal blood flow. Rather, it appears to be a characteristic response of this vessel. The biphasic response was not observed in other vascular beds studied and was not modified by atropine. beta-Adrenergic blockade enhanced the vasoconstrictor portion of the response, but this did not significantly alter the secondary blood flow increase.
Shigella dysenteriae I enterotoxin: proposed role in pathogenesis of shigellosis
Authors: Mathias J. R. , Carlson G. M. , Martin J. L. , Shields R. P. , Formal S.
Published: December 2017

Bacterial strains of Shigella dysenteriae I (3818-T and 3818-O) and Shigella enterotoxin altered myoelectric activity of the small intestine in New Zealand White rabbits. These agents were compared with activity caused by sterile culture broth or sterile saline. The altered myoelectric activity was characterized by two distinct complexes: repetitive bursts of action potentials (RBAP), characteristic of invasive strains of bacteria, and the migrating action potential complex (MAPC), characteristic of noninvasive bacteria. RBAP activity was the predominant myoelectric complex observed with S. dysenteriae strain 3818-T, an invader and toxin producer; S. dysenteriae strain 3818-O, a noninvader and toxin producer; and by Shigella enterotoxin. MAPC activity was present but was significantly less in all cases. These studies of the small intestine demonstrate an alteration in myoelectric activity characterized principally by RBAP activity indicative of invasion.
Stimulation of pancreatic growth by intraduodenal amino acids and HCl
Authors: Johnson L. R. , Dudrick S. J. , Guthrie P. D.
Published: December 2017

Exogenous secretin and cholecystokinin (CCK) have been shown to stimulate the growth of the exocrine pancreas. To conclude that a hormone produces an effect under normal physiological conditions, one must demonstrate that the endogenous hormone also produces the action in question. To release endogenous secretin 0.01 N HCl was continuously infused into the duodenums of eight rats for 5 days. Sixteen animals were prepared with catheters inserted 1 cm below the pylorus. The other eight animals were infused with PO4 buffer, pH 7.5. The infusion rate for both groups was 2 ml/h. Animals were killed at the end of 5 days, and the oxyntic gland mucosa and pancreas were examined. Pancreatic weights, DNA synthesis, DNa, RNA, and protein content were significantly increased in rats receiving acid. An identical experiment was set up to release endogenous CCK. In this experiment eight rats received a solution containing 50 mM phenylalanine and 50 mM tryptophan. The controls received the caloric equivalent in glucose. At the end of 1 wk the pancreases of the rats infused with amino acids averaged 405 (P < 0.001) heavier than the controls. Similar increases occurred in DNA, RNA, and protein content. These studies suggest that endogenous secretin and CCK can be released in amounts sufficient to stimulate growth.
Effect of acute metabolic alkalosis and acidosis on intestinal electrolyte transport in vivo
Authors: Feldman G. M. , Charney A. N.
Published: December 2017

The effects of acute metabolic alkalosis and acidosis on intestinal electrolyte transport were studied in adult Sprague-Dawley rats. Animals were made alkalotic or acidotic by gavage feeding of 1 M solutions of NaCl (pH = 7.42), NaHCO3 (pH = 7.52), NH4Cl (pH = 7.18), or 0.75 M (NH4)2SO4 (pH = 7.21). After 1-3 h, animals were anesthetized and prepared for in vivo perfusion of the jejunum, ileum, and colon. The jejunum exhibited increased net potassium absorption in alkalosis and decreased potassium absorption in acidosis. In the ileum, net sodium absorption and potassium secretion were decreased, and bicarbonate secretion was increased in alkalosis, and opposite effects were observed in acidosis. The ileal lumen minus blood gradient for PCO2 (an index of hydrogen ion secretion) was greater in acidotic than in alkalotic animals. The levels of ileal sodium, bicarbonate, and potassium transport and the PCO2 gradient correlated well with the plasma pH and bicarbonate concentration in individual animals. In the colon, net bicarbonate secretion and chloride absorption increased and potassium secretion decreased in alkalosis, and opposite effects were observed in acidosis. The colonic lumen minus blood PCO2 gradient was not affected by acid-base balance. Colonic bicarbonate transport correlated with the plasma chloride concentration as well as with the plasma pH. The acid-base disorders had no effect on transmural potential difference. These results suggest that acute metabolic alkalosis and acidosis alter sodium and hydrogen ion transport in the ileum and chloride and bicarbonate transport in the colon.
Calcium transport in small intestine during early development: role of vitamin D
Authors: Halloran B. P. , DeLuca H. F.
Published: December 2017

To define the role of vitamin D in calcium transport in the intestine during early development, female weanling rats were placed on vitamin D-replete or vitamin D-deficient diets, grown to maturity, and mated with normal males. Pups born to vitamin D-replete and vitamin D-deficient mothers were killed at various times after parturition, and calcium transport in the small intestine as well as the concentrations of calcium and phosphate in the plasma were measured. Transport of calcium in pups from vitamin D-replete and vitamin D-deficient litters was identical at 3 and 14 days postpartum but was threefold greater in pups from vitamin D-replete litters at weaning and 3 wk postweaning. 1,25-dihydroxyvitamin D3 had no effect on calcium transport at 14 days postpartum but did induce transport at weaning. Plasma concentrations of calcium at 3 days postpartum were nearly normal but decreased during the suckling period from 10.3 mg/100ml to 7.2 mg/100 ml in vitamin D-deficient rats. These results suggest that calcium transport in the intestine during early development is not mediated by vitamin D but that a vitamin D-sensitive transport system develops late in the suckling period.
Clearance and metabolism of circulating pancreatic proelastase in the rat
Authors: Largman C. , Ray S. B. , Brodrick J. W. , Geokas M. C.
Published: December 2017

A rat model has been employed to study the mechanism of clearance of pancreatic proelastase from the circulation. The clearance of 125I-labeled proelastase was shown to be biphasic, with a half-life for clearance of free 25,000-dalton proelastase of approximately 7–10 min. A slow component of clearance possibly due to proelastase associated with plasma protease inhibitors was also observed. At 10 min after injection of 125I-labeled proelastase into the circulation, the major fraction of the 125I was found to be localized in the kidney. However, appearance of 125I in urine is slow, with 16 h being required for excretion of 50% of the injected 125I as acid-soluble material. Subcellular localization experiments on homogenates of kidneys removed at 10 min postinjection revealed that the majority of the 125I-labeled material was associated with the mitochondrial and lysosomal fraction. Sucrose-gradient centrifugation studies of this fraction demonstrated that the labeled material passes from the membrane fraction to the lysosomal fraction with time. These data demonstrate that the rat kidney constitutes the major site for both circulatory clearance and catabolism of circulating pancreatic proelastase.
Turnover of intestinal brush-border proteins during postnatal development in rat
Authors: Seetharam B. , Yeh K. Y. , Alpers D. H.
Published: December 2017

Protein turnover in brush-border membranes of rats during postnatal development has been studied by the double isotope technique. Unlike adult animals where only large proteins (mol wt > 140,000) show relatively rapid turnover, most brush-border proteins in 12-day-old rats show high 3H-to-14C ratios of leucine incorporation, consistent with rapid turnover. Lysosomal proteases, including cathepsin B, are partly responsible for this rapid turnover. This conclusion is based on the following findings: 1) In vivo treatment of 12-day-old animals with leupeptin, an inhibitor of cathepsin B, alters relative turnover rates, enzyme activity, and content of many brush-border proteins. Activities of maltase and trehalase rise while lactase falls. 2) Cathepsin B activity falls rapidly in intestine after the animals are 16 days of age, at a time when luminal pancreatic proteases are rising. Moreover, cathepsin B activity shows less latency in distal intestine at 12 and 16 days than at later ages or in proximal intestine. It is suggested that during postnatal development lysosomal enzymes, e.g., cathepsin B, play an important role in the turnover of intestinal brush-border proteins.
Development of brush-border membrane hexose transport system in chick jejunum
Authors: Shehata A. T. , Lerner J. , Miller D. S.
Published: December 2017

Hexose transport was characterized in jejunal slices and brush-border membrane (BBM) vesicles from chicks of several ages (range: 2 days before hatch to 21 days after hatch). With slices, initial rates of 0.1 mM 3-O-methyl-D-glucose transport were low in --2-, and 0-day chicks, increasing to maximal levels 2-7 days after hatching; rates declined to adult levels over the next 2 wk. Phlorizin did not inhibit uptakes in --2- or 0-day slices. In contrast, about 80% of the uptakes in tissue from 2-day or older chicks was phlorizin inhibitable. The apparent Kt for phlorizin-sensitive transport was the same in slices from 2- (maximal transport rates) and 21-day (minimal posthatch rates) chicks; the apparent Vmax was 2.5 times greater in 2-day slices. With BBM vesicles, initial rates of Na-dependent D-glucose transport and maximal overshoot levels were greater in 2-day vesicles than in 21-day vesicles. As in slice experiments, Kt values were the same in the two preparations, but Vmax values were 1.4 times higher in the 2-day preparation.
Pancreatic enzyme secretion: nonspecific stimulation by duodenal mucosal extracts
Authors: La Bella A. , Lahaie R. G. , Sarles H. , Dagorn J. C.
Published: December 2017

Felber et al. (Lancet 2: 185-188, 1974) reported that duodenal extracts obtained from rats fed a given meal induced the specific secretion of related pancreatic enzymes. Such an observation challenges the generally accepted theory of parallel secretion of pancreatic enzymes. Although these experiments were faithfully reproduced, no induction of specific enzyme secretion could be obtained. Moreover, comparison of the secretagogue potency of different preparations of duodenal extract, both in vivo (anesthetized rat) and in vitro (pancreatic lobules), demonstrated that in the original extraction procedure most of the secretagogue activity was lost. Finally, even the fully active extract failed to induce specific enzyme secretion. It is therefore unlikely that duodenal extracts from rats fed a specific meal can induce selective secretion of the related enzyme.
Hormone-stimulated release of pancreatic polypeptide before and after vagotomy in dogs
Authors: Guzman S. , Lonovics J. , Devitt P. G. , Hejtmancik K. E. , Rayford P. L. , Thompson J. C.
Published: December 2017

Concentrations of pancreatic polypeptide (PP) in peripheral blood were measured before, during, and after infusions of graded doses of synthetic human gastrin I (SHG-I), cholecystokinin 99% pure (CCK-99%), CCK octapeptide (CCK-OP), and pure natural porcine secretin in six dogs with gastric and duodenal fistulas. Studies were repeated after truncal vagotomy. Significant increases in concentrations of PP were found with 1 microgram . kg-1 . h-1 of SHG-I, 0.25 and 1.0 microgram . kg-1 . h-1 of CCK-99%, and 0.06 and 0.25 micrograms . kg-1 . h-1 of CCK-OP. Significant increases persisted after vagotomy, except at the lower dose of CCK-OP. Postvagotomy responses were significantly less than prevagotomy, except at the higher doses of CCK-99% and CCK-OP. Pure secretin did not change concentrations of PP in blood before or after vagotomy. The most potent stimulant for PP release on a molar basis was CCI-99%, followed by CCK-OP and SHG-I. The results suggest that cholinergic and humoral agents of the gastrin-cholecystokinin family interact in the normal physiological response of PP to food and that, in dogs, CCK-like peptides are more potent than gastrin.
Weak electrolyte permeation in alimentary epithelia
Authors: Jackson M. J. , Tai C. Y. , Steane J. E.
Published: December 2017

The potential significance of ionized species in weak electrolyte absorption or secretion has been reexamined using a mathematical model that represents the epithelium as a system of parallel ion-permeable and ion-impermeable channels. An important determinant of weak electrolyte movement in this system is the ratio of ionized and nonionized permeabilities (Pi/Pni). This variable, which has been termed the discrimination coefficient, interacts with the degree of ionization in determining the contributions of ionized and nonionized species to the transepithelial movement of a weak electrolyte. Calculations based on the model suggest that ionized species may contribute significantly to the absorption or secretion of many common weak electrolytes. It is concluded that the frequently made assumption that ionized species do not contribute significantly to transepithelial movements of weak electrolytes in the alimentary tract is not generally valid. Further work is required to delineate the quantitative determinants of discrimination in alimentary epithelia, and two methods for evaluation of epithelial discrimination coefficients are described.
Effect of veratrine and 50 mM K on ileal transport and electrically induced secretion
Authors: Hubel K. A.
Published: December 2017

To obtain additional evidence that the Cl secretion caused by electrical field stimulation (EFS) in rabbit ileum in vitro is mediated by nerves or amine precursor uptake and decarboxylation (APUD) cells, we determined whether the response could be prevented by agents that depolarize nerves, veratrine or 50 mM K. EFS 1) increased transmural electrical potential difference (PD) and the short-circuit current (Isc) and reduced total ion conductivity (G), 2) caused Cl secretion by reducing the mucosal-to-serosal flow of chloride (JClm leads to s) alone or in combination with an increase in the serosal-to-mucosal flux of chloride (JCls leads to m), and 3) reduced Na absorption or caused secretion by increasing JCls leads to m alone or in association with a reduction in JNam leads to s. At 10(-5) g/ml, veratrine prevented the changes in ionic fluxes caused by EFS and reduced the PD and Isc. It did not reduce the Isc response to 5 mM aminophylline, however. Fifty millimolar K decreased PD and Isc and increased G. JNam leads to s and JNas leads to m diminished in proportion to the reduction in bath Na concentration, so the net flux of sodium (JNanet) was not affected. JClnet did not change, although both JClm leads to s and JCls leads to m increased. Fifty millimolar K prevented the changes in ionic fluxes caused by EFS and reduced the Isc response to aminophylline by half. The study provides additional evidence that the effects of EFS are mediated by nerves or electrically excitable APUD cells, but the contribution of each is uncertain.
Postprandial hormonal inhibition of canine interdigestive gastric motility
Authors: Schang J. C. , Kelly K. A. , Go V. L.
Published: December 2017

Our aim was to determine whether hormones other than gastrin inhibit cyclic interdigestive motility in the proximal stomach. In four conscious dogs with autotransplanted proximal gastric pouches, excluded gastric antrums, and chronic duodenal electrodes, intraluminal pressure of the pouch and electrical activity of the duodenum were monitored before and after gastric instillation of 250 ml of 154 mM NaCl alone or 154 mM NaCl plus 15 kcal/kg of either dextrose, olive oil, casein hydrolysate, or a mixture containing 5 kcal/kg of each of the three nutrients. Dextrose, olive oil, casein, and the mixture abolished the interdigestive cycles in both pouch and duodenum and decreased intrapouch pressure compared with the saline control. The duration of the inhibition was longest with oil (5 h) and shortest with casein (3 h), and the decrease in mean intrapouch pressure was greatest with the mixture (11.8 cmH2O . min) and least with dextrose (9.3 cmH2O . min). Serum gastrin was unchanged by any of the instillates. We concluded that hormones other than gastrin inhibited cyclic interdigestive motility in the proximal stomach.
A device for jointless connections with unrestrained animals
Authors: Molimard R. , Martin C. , Pesez A. , Miramand J. L.
Published: December 2017

An apparatus is described allowing multichannel connection with unrestrained animals without using joints. The twisting of the connection lines caused by the rotation of the animal in its cage is detected by means of a torsion wire connected to an electronic device. This provokes a temporized rotation of the bottom of the cage in the opposite direction in order to untwist the lines.
Effect of atropine on esophageal motor function in humans
Authors: Dodds W. J. , Dent J. , Hogan W. J. , Arndorfer R. C.
Published: December 2017

In this study, we used a high-fidelity manometric recording system to quantitate the effects of atropine on lower esophageal sphincter (LES) pressure and primary peristalsis (1 degree P). A sleeve sensor recorded LES pressure, and seven recording orifices spaced at 3-cm intervals registered motor activity in the esophageal body. Five randomized manometric studies were done in each of five normal subjects. LES pressure and 1 degree P with wet swallows were recorded for 30 min before and 70 min after intravenous injection of saline or atropine, 3, 6, 12, and 24 micrograms/kg. We also studied the effect of atropine on LES pressure in five additional subjects, four dogs, four opossums, and six monkeys. In humans, saline and 3 micrograms/kg atropine caused no significant change in pulse rate, LES pressure, or the incidence of complete peristaltic sequences. The 6, 12, and 24 micrograms/kg atropine doses caused significant inhibition of LES pressure and the incidence of intact 1 degree P. Only the 12 and 24 micrograms/kg doses increased pulse rate. When 1 degree P occurred in the smooth muscle portion of the esophagus its appearance in the proximal portion of the smooth muscle segment was delayed for several seconds. The amplitude of 1 degree P was decreased 30-60% in the smooth muscle segment, but 1 degree P was not affected in the proximal striated muscle esophageal segment. Atropine reduced canine LES pressure substantially but caused no change in opossums or monkeys. We conclude that 1) basal LES tone in humans and dogs, unlike that of the opossum and monkey, is partially generated by cholinergic neural input, 2) cholinergic nerves elicit 1 degree P in human esophageal smooth muscle, and 3) species variation exists in esophageal responses to atropine.
Lymph flow during fluid absorption from rat jejunum
Authors: Lee J. S.
Published: December 2017

The relation between intestinal lymph flow (JL) and fluid absorption rate (JV) was studied with an in vivo jejunal preparation of the rats under pentobarbital sodium anesthesia. It was found that in more than 60% of the rats there is a communication between hepatic and intestinal lymphatics. JL was significantly higher in these rats whether the intestine was in the nonabsorptive state or during fluid absorption. This is undoubtedly due to the contribution of hepatic lymph. The increased lymph flow due to fluid absorption in the rats without hepatic lymphatic communication varied over a wide range of 0-27% of the absorbed volume with a mean value of 8%. In the rats with simultaneous fat absorption, JV did not change but JL decreased to about 3% of the absorbed volume. There was no correlation between JL and JV. Furthermore, obstruction of JL caused no change in JV, indicating that the lymphatic system is not indispensable in fluid transport. From these findings, it is concluded that JL is not a constant proportion of the absorbed volume but depends on the pathophysiological state of the intestine.
Gastric oxyntic cell tubulin: characterization and possible significance
Authors: Stewart H. E. , Kasbekar D. K.
Published: December 2017

Colchicine-binding activity in the homogenate fractions of the whole gastric epithelium and oxynein tissue has been studied to determine if tubulin is present in the bullfrog stomach. Most of the specific binding activity is found in the 100,000-g soluble fraction and is enriched in the oxynein tissue. Binding is proportional to protein concentration, linear up to 30 min, and half saturable at 16 microM colchicine concentration. Scatchard and direct linear plot analysis yields the following values for binding constants: Kd = 12 microM, Ka = 0.08 X 10(6) M-1, maximal binding capacity (Bmax) = 0.19 X 10(-6) M, and n = 84 pmol/mg protein. Fiftyfold excess lumicolchicine does not affect colchicine binding. The binding activity has been partially purified by the temperature-sensitive cycling technique. Sodium dodecyl sulfate-polyacrylamide gel electrophoretic analysis of the product shows a major band corresponding to tubulin in the 55,000-dalton region. Tubulin in isolated oxyntic cells can be visualized by indirect immunofluorescence. These data and the observed increase in colchicine-binding activity in the burimamide- over the histamine-treated tissue, possibly due to changes in the levels of tubulin polymerization, suggest a likely involvement of the cytoskeleton in gastric secretion.
Intestinal microcirculation and transmucosal fluid transport
Authors: Granger D. N.
Published: December 2017

Blood and lymph capillaries play an important role in removing absorbed fluid from the interstitium of the intestinal mucosa. Data from the literature indicate that hydrostatic and oncotic pressures within the mucosal interstitium primarily determine the partition of absorbed fluid between blood and lymph. Alterations in the density of perfused capillaries and/or capillary permeability during absorption also influence the effectiveness of blood capillaries in removing absorbed fluid. An hypothesis regarding the roles of the interstitium, lymphatics, and capillaries during fluid transport is presented that is based mostly on whole organ studies. The effects of interstitial fluid compartmentation on interpretations of whole organ data are also discussed.
Effects of autonomic drugs on cat colonic muscle
Authors: Anuras S. , Christensen J.
Published: December 2017

The cat colon was divided in vitro into four equal segments, and one transverse and one longitudinal strip (1.5 cm x 2.5 mm) was taken from each. Transverse strips contracted rhythmically, each strip generating 0.9–1.2 g force. Longitudinal strips contracted irregularly, each strip generating 11.9–16.8 g force. Acetylcholine (10(-7) to 10(-5) M) and physostigmine (10(-8) to 10(-5) M) increased frequencies in longitudinal (P less than 0.05) but not in transverse strips (P greater than 0.05) and increased amplitudes in both (P less than 0.05). Atropine (10(-8) to 10(-6) M) reduced frequencies and amplitudes in longitudinal strips (P less than 0.05) but only amplitudes in transverse strips (P less than 0.05). Phenylephrine (10(-7) to 10(-5) M) and norepinephrine (10(-7) to 10(-5) M) increased amplitudes in transverse strips (P less than 0.05) but decreased frequencies and amplitudes in longitudinal strips (P less than 0.05). Isoproterenol (10(-7) to 10(-5) M) decreased frequencies an amplitudes in both transverse and longitudinal strips (P less than 0.05). Dopamine (10(-7) to 10(-5) M) decreased amplitudes in longitudinal strips (P less than 0.05). Tetrodotoxin (10(-7) M increased amplitudes in transverse (P less than 0.05) but not in longitudinal strips (P greater than 0.05). Both layers are affected by cholinergic and adrenergic drugs. Muscarinic receptors are excitatory in both. alpha-Adrenergic stimulations result in excitation in circular muscle and inhibition in longitudinal muscle. Circular muscle is dominated by an inhibitory neural tone.
Effect of atropine on pancreatic response to HCl and secretin
Authors: Singer M. V. , Solomon T. E. , Rammert H. , Caspary F. , Niebel W. , Goebell H. , Grossman M. I.
Published: December 2017

In dogs with gastric and pancreatic fistulas, we studied the effect of atropine on the pancreatic secretory response to secretin and intestinal HCl. Atropine sulfate (20 micrograms.kg-1.h-1 iv) significantly depressed basal bicarbonate and protein output. Atropine depressed bicarbonate responses to low doses (62.5, 125, 250, and 500 ng.kg-1.h-1) of secretin but had no significant effect on responses to high doses (1,000 and 2,000 ng.kg-1.h-1). Secretin, with or without atropine, did not stimulate pancreatic protein output above basal. Atropine depressed bicarbonate responses to low loads (3, 6, and 12 mmol.h-1) of HCl but had no significant effect on responses to high loads (12, 24, and 48 mmol.h-1). Intraduodenal HCl produced a dose-dependent increase in protein output. Atropine abolished protein responses to low loads (3 and 6 mmol.h-1) but did not affect responses to high loads (24 and 48 mmol.h-1) of HCl. These findings are compatible with the hypotheses that a) endogenous cholinergic activity augments the pancreatic bicarbonate response to secretin, and b) the pancreatic protein response to intraduodenal HCl is, at least in part, mediated cholinergically.
Effects of histamine and histamine antagonists on intestinal capillary permeability
Authors: Mortillaro N. A. , Granger D. N. , Kvietys P. R. , Rutili G. , Taylor A. E.
Published: December 2017

Steady-state lymph flow, blood flow, and lymph and plasma total protein concentration were measured in an autoperfused cat ileum preparation during the continuous infusion of histamine at venous pressures of 0, 10, 20, and 30 mmHg. The capillary osmotic reflection coefficients for total proteins and each protein fraction were estimated. In addition, the ileum was pretreated with an H1-receptor antagonist (diphenhydramine) or with an H2-receptor antagonist (cimetidine). The results suggest that histamine selectively increases the ileal vascular permeability to plasma proteins of a molecular radius up to 96 A. The H1-receptor antagonist did not alter the histamine-induced permeability changes but did block the observed initial vasodilation. The H2-receptor antagonist significantly reduced the permeability changes associated with histamine while having only a slight effect on the initial vasodilation. It is concluded that the activation of H1-receptors is predominantly associated with the initial vasodilation, whereas the H2-receptors are predominantly associated with permeability.
Effects of porcine secretin on exocrine and endocrine function in the isolated perfused rat pancreas
Authors: Otsuki M. , Sakamoto C. , Ohki A. , Yuu H. , Morita S. , Baba S.
Published: December 2017

The effects of both synthetic and pure natural porcine secretin on immunoreactive insulin (IRI) and immunoreactive glucagon (IRG) release and on pancreatic exocrine secretion were studied in the isolated perfused rat pancreas. Synthetic porcine secretin stimulated a significant increase in pancreatic juice flow and amylase output at concentrations as low as 0.01 and 0.1 ng/ml, respectively. The maximal peak rate of both juice flow and amylase output was observed at 1 microgram/ml synthetic secretin. Synthetic secretin at concentrations up to 2 micrograms/ml and pure natural porcine secretin at a concentration of 1 clinical unit/ml had no effect on IRI secretion regardless of the glucose concentration (50, 100, or 150 mg/100 ml) in the perfusate. Both types of secretin, however, elicited a concentration-dependent increase in IRG secretion in the presence of 50 mg/100 ml glucose. The lowest synthetic secretin concentration causing a significant increase in IRG release was 0.1 ng/ml, and maximal stimulation was observed at 1 microgram/ml. These concentrations were similar to those eliciting minimal and maximal amylase release. Thus, synthetic and pure natural porcine secretin have been shown to not only stimulate pancreatic juice flow and amylase secretion but also to elicit IRG release from the isolated perfused rat pancreas.
Effect of substance P and its C-terminal hexapeptide on gastric and pancreatic secretion in the dog
Authors: Konturek S. J. , Jaworek J. , Tasler J. , Cieszkowski M. , Pawlik W.
Published: December 2017

In five dogs with gastric fistulas, Heidenhain pouches, and pancreatic fistulas, the effects of substance P (SP) and its C-terminal hexapeptide (SP6-11) on gastric acid and pancreatic secretions were determined under basal conditions and in response to secretory stimulation. SP or SP6-11 infused alone in graded doses (0.25-2.0 nmol.kg-1.h-1) caused a slight but significant increase in pancreatic secretions in fasted dogs, but, when given during the secretory stimulation, they caused significant inhibition of these secretions. They reduced gastric acid response to pentagastrin and peptone meal without affecting the serum gastrin level. They caused dose-dependent inhibition of secretin-induced pancreatic bicarbonate secretion and suppressed the pancreatic protein response to caerulein, feeding, and duodenal acidification. SP6-11 was equipotent on a molar basis with SP in the inhibition of gastric or pancreatic secretion, indicating that the C-terminal portion of SP exhibits a full spectrum of the biological action of the intact molecule. The inhibitory effects of SP and SP6-11 on the stomach and pancreas were observed at a dose range that was without any significant influence on the blood pressure, indicating that they are not caused by the interference of the blood flow to the pancreas.
Regulation of protein synthesis in normal and diabetic rat pancreas by cholecystokinin
Authors: Korc M. , Bailey A. C. , Williams J. A.
Published: December 2017

The effects of cholecystokinin (CCK) on [3H]leucine incorporation into protein were studied in isolated pancreatic acini from normal and streptozotocin-induced diabetic rats. CCK8, the biologically active C-terminal octapeptide of CCK, increased [3H]leucine incorporation into protein over a concentration range that stimulates digestive enzyme secretion (1 X 10(-11) to 1 X 10(-10) M); at higher concentrations, CCK8 inhibited incorporation. Stimulation of [3H]leucine incorporation was greatest in acini from diabetic rats, intermediate in acini from fed normal rats, and least in acini from fasted rats. The magnitude of inhibition was similar in all acini. A significant stimulatory effect of CCK8 in acini from diabetic rats was detected after 10 min and was maximal after 40 min of incubation. Carbachol mimicked both the stimulatory and inhibitory effects of CCK, whereas the Ca2+ ionophore A23187 mimicked only the inhibitory effects. Insulin also stimulated [3H]leucine incorporation in acini from diabetic rats, and its effects were additive to the stimulatory effect of CCK. The present findings suggest that physiological concentrations of CCK and other pancreatic secretagogues may participate in the regulation of pancreatic protein synthesis.
Effect of histamine on motor function of opossum sphincter of Oddi
Authors: Toouli J. , Dodds W. J. , Honda R. , Hogan W. J.
Published: December 2017

In this study, we evaluated the effect of histamine on phasic contractile activity in the opossum sphincter of Oddi (SO). SO manometry was done in 35 animals, using an infused catheter system with minimal compliance. In anesthetized animals, phasic SO contractions occurred at a frequency of 7.3 +/- 0.3 (SE) contractions/min with an amplitude of 83 +/- 4 mmHg. Intravenous histamine (5-80 micrograms/kg) invariably inhibited the frequency and amplitude of SO phasic contractions. At larger doses, the SO contractions were abolished for several minutes. The SO inhibitory effect of histamine was duplicated by the selective H1-agonist, 2-pyridylethylamine, and abolished by H1-blockade with pyrilamine or neural blockade with tetrodotoxin. After tetrodotoxin, histamine and 2-pyridylethylamine caused an increased frequency and amplitude of SO contractions. This excitatory effect was blocked by pyrilamine. The histamine effects on SO phasic contractions were not altered by metiamide, atropine, phentolamine, propranolol, hexamethonium, or a large dose of nicotine. We conclude that 1) histamine depresses phasic SO contractions in the opossum; 2) histamine's depressant SO effect is mediated by H1 stimulation of noncholinergic, nonadrenergic SO inhibitory nerves, overriding an H1 stimulatory effect on SO smooth muscle; and 3) histamine has no H2-mediated effect on the opossum SO.
Functional properties of noradrenergic nervous system in rat colonic mucosa: uptake of [3H]norepinephrine
Authors: Wu Z. C. , Gaginella T. S.
Published: December 2017

The accumulation of exogenous [3H]norepinephrine ([3H]NE) by rat colonic mucosa was studied. Uptake was linear for 10 min and reached a maximum after 90 min. The process was concentration dependent and saturable, having a Km of 1.67 X 10(-6) M and Vmax of 0.57 nmol.g-1.min-1. The inhibitor of specific norepinephrine uptake, desmethylimipramine (DMI), inhibited uptake in a concentration-dependent manner; the maximum inhibition was 81% at 10 microM. Normetanephrine also inhibited uptake at 100 microM. Reserpine, at concentrations ranging from 10(-7) to 10(-5) M, prevented the accumulation of [3H]NE, with maximum inhibition being 47% of control. Accumulation by mucosa obtained from rats sympathectomized with 6-hydroxydopamine was only 33% of control; DMI did not further reduce this uptake. Colonic epithelial cells were isolated and were found to also accumulate [3H]NE, but this accumulation was not affected by DMI. It is concluded that rat colonic mucosa contains noradrenergic neurons capable of accumulating exogenously administered norepinephrine by a specific and high-affinity process. The presence of a functional noradrenergic neural network in close association with the epithelium suggests that this system may play a physiological role in modulating colonic mucosal function.
Organic acid proton donors decrease intestinal secretion caused by enterotoxins
Authors: Forsyth G. W. , Kapitany R. A. , Hamilton D. L.
Published: December 2017

The effects of several weak acids on the secretory actions of cholera toxin and the heat-stable enterotoxin of Escherichia coli (ST) have been examined in ligated jejunal loops in weanling pigs. Ascorbic and acetic acids had no effect, but L-lactic acid reduced the net fluid secretion caused by cholera toxin. Glutaric acid and p-aminobenzoic acid blocked net fluid secretion caused by cholera toxin or by ST. Antisecretory effects were pH dependent for p-aminobenzoic acid in this study and for nicotinic acid in a previous report (6). At a pH of 5.0, p-aminobenzoic acid treatment increased lumen-to-blood sodium flux and decreased the blood-to-lumen sodium flux caused by cholera toxin. These weak acid effects were more marked on fluid fluxes in enterotoxin-treated loops than in control loops and persisted for 20–30 min after acid removal from loops. These findings are discussed in terms of requirements for antisecretory activity and possible modes of action of antisecretory compounds.
Pyloric pressure response to insulin-induced hypoglycemia in humans
Authors: Phaosawasdi K. , Goppold R. , Fisher R. S.
Published: December 2017

The pyloric pressure response to insulin-induced hypoglycemia was studied. Studies were performed in 102 experiments on 38 normal subjects. During insulin-induced hypoglycemia, pyloric pressure increased from 5.5 +/- 1.2 to 10.8 +/- 1.1 mmHg (P less than 0.02). This increase in pyloric pressure ws not due to a direct effect of insulin, duodenal acidification, or the release of corticosteroids or growth hormone. Glucagon doses of 2 and 5 micrograms . kg-1 . h-1 increased pyloric pressure from 4.7 +/- 1.1 to 6.7 +/- 0.5 mmHg (P less than 0.05) and from 4.7 +/- 1.1 to 8.5 +/- 1.1 mmHg (P less than 0.02), respectively. Pyloric pressures were increased to 10.8 +/- 0.9 (P less than 0.01) and 13.0 +/- 1.4 mmHg (P less than 0.01) at 0.1 and 0.2 micrograms . kg-1 . min-1 of epinephrine, respectively. Neither cholinergic blockade nor alpha-adrenergic blockade significantly affected the pyloric pressure response to insulin hypoglycemia. beta-Adrenergic blockade abolished the pyloric pressure responses to both insulin hypoglycemia and epinephrine. Neither beta- nor alpha-adrenergic stimulation altered the basal pyloric pressure. In contrast, the combination of isoproterenol and phenylephrine increased the pyloric pressure significantly from 4.2 +/- 0.8 to 12.0 +/- 1.7 mmHg ( P less than 0.01). These observations suggest that insulin hypoglycemia increases pyloric pressure by an adrenergic mechanism that requires stimulation of both alpha- and beta-receptors.
Nature of bile acid maximum secretory rate in the rat
Authors: Hardison W. G. , Hatoff D. E. , Miyai K. , Weiner R. G.
Published: December 2017

We studied the determinants of maximum bile acid secretory rate (SRm) in the rat. The choledochocaval fistula rat model manifested a bile acid secretory rate far in excess of the SRm previously reported for taurocholate in this species. We studied the ability of various bile acid solutions to maintain the high secretion rate in this model. Whole-rat bile, but not taurocholate in 2% albumin nor rat bile with bile acid content over 90% taurocholate, maintained secretion rate. We concluded that the mixture of bile acids in rat bile was the most important determinant of the high secretion rate and that the high rate was not due to a peculiarity of the model itself nor to the infusion of biliary lipids together with bile acids. Conventional determination of the SRm in the bile fistula rat confirmed this impression, with the least toxic bile acids manifesting the highest SRm. During infusion of taurocholate beyond the SRm, bile flow and bile acid secretion rate fell. This was accompanied only by scattered focal necrosis of single liver cells or of small aggregates of cells and not by any diffuse subcellular morphological change. We believe the maximum bile acid secretory rate is determined by toxicity of a specific bile acid for the secretory mechanism rather than by a limitation in transport receptor number as is usual with substances manifesting classical transport maxima. The high SRm of the 7 beta-hydroxy bile acid, ursodeoxycholic acid, is probably related to its very low toxicity. The high SRm in the choledochocaval fistula rat is probably related to the presence of 7 beta-hydroxy muricholic acids in the bile of this species.
Involvement of extracellular calcium in gastric stimulation
Authors: Logsdon C. D. , Machen T. E.
Published: December 2017

We have tested whether external Ca2+ is required for either initiation or maintenance of secretory parameters, including membrane elaboration of oxyntic cells, in frog gastric mucosa. Ca2+ was removed from in vitro mucosal preparations [by washing repeatedly in Ca2+-free Ringer solution and adding 0.1 mM ethylene glycol-bis(beta-aminoethylether)-N,N'-tetraacetic acid to the serosal solution] either before (i.e., resting tissues) or after addition of stimulants. Electrophysiology [transepithelial potential difference (PD) and resistance], morphology (morphometric analysis of transmission electron micrographs), and transport (H+ secretion) were monitored. La3+ (1 mM) was added to the mucosal solution to help maintain resistance and PD. La3+ decreased tissue shunt conductance during Ca2+-free conditions, as evidenced by a decreased mucosal-serosal flux of 22Na+, presumably by preserving tight-junction integrity. Secretion was elicited by histamine alone or in combination with dibutyryl cAMP and isobutylmethylxanthine (a phosphodiesterase inhibitor). External Ca2+ is not required for the initiation of H+ secretion or the accompanying morphological changes when the combined stimulants are used, whereas H+ secretion and the morphological change showed some Ca2+ dependency when histamine alone was used. Thus, histamine-elicited secretion seems to be more sensitive to Ca2+ removal than that brought about by the combined stimulants. Long-term effects of Ca2+-free solutions on resistance, PD, and H+ secretion can largely be explained by disruptive effects on tight junctions.