bluuebunny/crossref_metadata_2025 huggingface dataset:
Dietary modulation of alpha-cell volume and function in strain 129/J mice
Authors: Morley M. G. , Leiter E. H. , Eisenstein A. B. , Strack I.
Published: December 2017

Weanling female 129/J mice were maintained for 1, 2, 3, or 6 mo on either a control diet containing 60% sucrose and 23% protein or an isocaloric, high-protein, no-carbohydrate diet containing 83% protein and 0% sucrose. Mice were killed after each interval to assess the effect of diet on histological and physiological changes in the endocrine pancreas. Image analysis of islets stained immunocytochemically for alpha-cells, beta-cells, delta-cells, and PP cells was performed to quantify changes in islet structure. It was found that islet composition was strongly affected by diet. The volume density of the alpha-cells was significantly elevated in mice fed the high-protein diet (e.g., 35% vs. 16% in controls at 6 mo), whereas the volume density of beta-cells concomitantly decreased from 65 to 39%. Radioimmunoassay of the insulin and glucagon content of the pancreas and the plasma corroborated the morphometric findings. Pancreatic and plasma glucagon concentration in mice on the high-protein diet was elevated by an average of 2.5-fold above controls, whereas pancreatic insulin concentration was diminished by nearly half. The increase in alpha-cell volume density and pancreatic glucagon concentration appeared initially due to alpha-cell hypertrophy, although by 6 mo of high-protein feeding both hypertrophy and hyperplasia of the alpha-cells were evident. Presumably, these changes were compensatory responses to the increased functional demand on alpha-cells (i.e., glucagon biosynthesis and secretion) imposed by chronic high-protein feeding.
Responsiveness of longitudinal and circular muscle layers of the portal vein
Authors: Brown B. P. , Anuras S. , Heistad D. D.
Published: December 2017

This study was performed to compare mechanical activity produced by acetylcholine and histamine in longitudinal and circular muscle layers of the portal vein. Peak tension was measured in longitudinal and circular muscle strips from portal veins of rabbits as they were superfused with acetylcholine and histamine (10(-6) to 10(-4) M). Responses to acetylcholine were three to four times greater in longitudinal muscle than in circular muscle; for example, acetylcholine (10(-5) M) produced contractions of 1.6 +/- 0.2 X 10(3) (mean +/- SE) dynes in longitudinal muscle and 0.4 +/- 0.09 X 10(3) dynes in circular muscle. In the same strips, histamine produced similar responses in the two layers: histamine (10(-5) M) produced contractions of 0.4 +/- 0.1 X 10(3) dynes in longitudinal and 0.4 +/- 0.1 X 10(3) dynes in circular muscle. Histological studies of portal vein muscle strips showed that the longitudinal muscle layer is three to four times thicker than the circular muscle layer. Thus, in response to acetylcholine, tension developed in each muscle layer is proportional to the thickness of that layer. In response to histamine, however, longitudinal muscle develops less tension than is predicted by the thickness of the muscle layer. We conclude that longitudinal and circular muscle layers of the rabbit portal vein differ in their responsiveness to histamine.
Gastrin stimulation of isolated gastric glands
Authors: Chew C. S. , Hersey S. J.
Published: December 2017

The ability of gastrin to stimulate acid formation was studied in gastric glands and isolated parietal cells obtained from rabbit gastric mucosa. Accumulation of the weak base aminopyrine and increases in oxygen consumption were used as measures of acid secretory activity. The responses to gastrin were found to be very small (10-15% increase). However, inclusion of dithiothreitol (0.5 mM) in the incubation medium enhanced the responses in both glands and isolated cells to easily detectable levels. For the gastric gland preparation, gastrin stimulation was maximal at 1 X 10(-7) M, with an apparent ED50 of 5 nM. The response reached a maximum at about 30 min and was stable for at least an hour. The gastrin response was enhanced by the phosphodiesterase inhibitor isobutylmethylxanthine and partially inhibited by cimetidine, a histamine H2-receptor antagonist. Combinations of gastrin and histamine showed an additive response over a wide range of histamine concentrations. However, time-course studies revealed a transient potentiation of gastrin response by histamine, which reached a peak at 15 min and was reduced to an additive response by 30 min. Studies using isolated cell populations enriched in parietal cells (approximately 70%) revealed a gastrin stimulation that was not inhibited by cimetidine. The transient potentiation of the gastrin response by histamine was also found in the isolated cell preparation. Gastrin had no effect on cellular cAMP levels or adenylyl cyclase activity. The results are interpreted to indicate that gastrin stimulates acid secretion through three separate actions: 1) a direct stimulation of parietal cell activity, 2) a potentiating interaction with histamine, and 3) for more intact preparations, a release of histamine, which in turn acts as a paracrine stimulus. Quantitatively, the most important action appears to be the release of histamine. None of the actions of gastrin appear to involve a change in cAMP metabolism.
Regulation of Na+-Pi cotransport by 1,25-dihydroxyvitamin D3 in rabbit duodenal brush-border membrane
Authors: Hildmann B. , Storelli C. , Danisi G. , Murer H.
Published: December 2017

Brush-border membrane vesicles were isolated from rabbit duodenum by a Mg2+ precipitation method, and phosphate transport was analyzed by a rapid filtration technique. Uptake of inorganic phosphate (Pi) was stimulated by an inwardly directed sodium gradient, indicating the operation of a Na-Pi cotransport system in brush-border membrane vesicles. Treatment of the animals with ethane-1-hydroxy-1,1-diphosphonate (EHDP), which is known to decrease the circulating levels of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], reduced within 3 days the sodium-dependent Pi transport in the brush-border vesicles. Injections of 1,25(OH)2D3 into rabbits increased within 9 h the sodium-dependent Pi transport in membranes from EHDP-treated animals as well as in untreated ones. The Na-D-glucose cotransport system appeared to be unaffected by these maneuvers. These results suggest that the Na-Pi cotransport system is an important site of regulation of intestinal transepithelial Pi transport by 1,25(OH)2)D3.
Effects of inhibitors of cyclic nucleotide phosphodiesterase on the actions of vasoactive intestinal peptide and secretin on pancreatic acini
Authors: Gardner J. D. , Korman L. Y. , Walker M. D. , Sutliff V. E.
Published: December 2017

Theophylline, 3-isobutyl-1-methylxanthine (IBMX), and Ro 20-1724 each augmented the increase in cAMP and the stimulation of amylase secretion caused by vasoactive intestinal peptide (VIP) or secretin. With IBMX the dose-response curve for the stimulation of amylase secretion caused by VIP or secretin spanned a range of lower concentrations than did that obtained with Ro 20-1724, which in turn spanned a range of lower concentrations than did that obtained with theophylline. The configuration of the dose-response curve for the action of VIP on cAMP differed with each phosphodiesterase inhibitor tested. With Ro 20-1724 the dose-response curve was monophasic, whereas with the two methylxanthines the dose-response curve was biphasic. With theophylline the magnitude of the second component of the dose-response curve was larger than the first; with IBMX the magnitude of the first component was larger than the second. The configuration of the dose-response curve for the action of secretin on cAMP also differed with each phosphodiesterase inhibitor tested. With theophylline the dose-response curve was monophasic, whereas with Ro 20-1724 and IBMX the dose-response curve was biphasic. With Ro-20-1724 the magnitude of the second component of the dose-response curve was larger than the first; with IBMX the magnitude of the first component was larger than the second. These results indicate that cAMP is compartmentalized in pancreatic acinar cells and that the different compartments of cAMP are affected differently by various inhibitors of cyclic nucleotide phosphodiesterase. These findings also suggest that the different compartments of cAMP are acted on by phosphodiesterases with different sensitivities to various inhibitors.
Role of exchange vessels in the regulation of intestinal oxygenation
Authors: Granger D. N. , Kvietys P. R. , Perry M. A.
Published: December 2017

The contribution of changes in capillary exchange capacity to local regulation of oxygen uptake was assessed in the cat small intestine. Oxygen extraction, oxygen uptake, and the capillary filtration coefficient (KF,C) were measured at blood flows ranging between 4 and 70 ml.min-1.100 g-1. Blood flow was altered via pump perfusion or partial arterial occlusion. Both oxygen extraction and capillary exchange capacity (KF,C) increased progressively as blood flow was reduced in a stepwise fashion. Oxygen uptake remained constant between blood flows of 30 and 70 ml.min-1.100 g-1, yet it decreased progressively as blood flow was reduced below 30 ml.min-1.100 g-1. These findings support the hypothesis that intrinsic modulation of intestinal oxygen extraction is mediated by vascular elements that govern capillary exchange capacity.
Effects of chlorothiazide on 1,25-dihydroxyvitamin D3, parathyroid hormone, and intestinal calcium absorption in the rat
Authors: Favus M. J. , Coe F. L. , Kathpalia S. C. , Porat A. , Sen P. K. , Sherwood L. M.
Published: December 2017

Previous studies have shown that thiazide diuretic agents reverse secondary hyperparathyroidism and reduce circulating 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and intestinal calcium absorption rates in patients with idiopathic hypercalciuria of the renal-leak variety. We have investigated whether thiazides can reverse the secondary increase in serum parathyroid hormone (PTH) and 1,25(OH)2D3 levels or intestinal calcium absorption induced by feeding rats a diet low in calcium (LCD, 0.02% calcium) but adequate in phosphorus and vitamin D. We found that LCD increased circulating immunoreactive PTH [chow vs. LCD, 0.52 +/- 0.06 vs. 1.06 +2- 0.1 (SE) ng/ml, P less than 0.001], 1,25(OH)2D3 (chow vs. LCD, 101 +/- 15 vs. 325 +/- 38 pg/ml, P less than 0.001), calcium uptake by everted gut sacs from duodenum, ileum, and descending colon, and net calcium absorption by descending colon studied in Ussing chambers in vitro. Chlorothiazide (CTZ) prevented the increase in PTH during LCD (chow + CTZ vs. LCD + CTZ, 0.69 +/- 0.07 vs. 0.73 +/- 0.06, NS) but not the increase in 1,25(OH)2D3 (chow + CTZ vs. LCD + CTZ, 88 +/- 10 vs. 277 +/- 31, P less than 0.002) or intestinal calcium transport. The drug caused no change in serum 1,25(OH)2D3 or intestinal calcium absorption in rats fed normal chow. In rats given exogenous 1,25(OH)2D3 to stimulate intestinal calcium absorption, CTZ reduced urine calcium excretion greatly but did not alter intestinal calcium absorption.
Effects of atropine on the action and release of secretin in humans
Authors: You C. H. , Rominger J. M. , Chey W. Y.
Published: December 2017

Using two groups of volunteers, we investigated the effects of atropine on pancreatic secretion of bicarbonate, protein, and trypsin stimulated by secretin. Secretin given intravenously in graded doses of 0.03, 0.06, and 0.125 clinical units.kg-1.h-1 produced significant increases in pancreatic secretion of bicarbonate in a dose-related manner. Pancreatic secretion of bicarbonate and protein was significantly suppressed by intravenous atropine, despite the dose of secretin infused. Intrajejunal perfusion of HCl at a rate of 3.3 mM/h, producing plasma secretin concentration comparable with that of the postprandial state, resulted in significant increases in the pancreatic secretion of bicarbonate. The increase in the pancreatic secretion of bicarbonate and trypsin was significantly suppressed by atropine. However, atropine did not affect the increase in the plasma secretin concentration produced by jejunal acidification or intravenous secretin. These studies indicate that atropine inhibits the pancreatic effect but not the intestinal release of secretin.
Digests of protein augment acid-induced canine pancreatic secretion
Authors: Fink A. S. , Miller J. C. , Jehn D. W. , Meyer J. H.
Published: December 2017

To study interactions between intraluminal acid and protein digests, six dogs with chronic gastric and pancreatic fistulas received three sets of intestinal perfusates. The first set contained HCl (1, 2, or 4 mmol/50 ml) and 64 mM D- or L-phenylalanine. The second set contained HCl plus either intact or pepsin-digested bovine serum albumin (BSA); the BSA and HCl were varied so that each 50 ml contained 1, 2, or 4 meq of acid titratable from an initial pH of 2.0 to an end-point pH of 4.5. The third set was identical to the second set except for an initial pH of 3.5. All perfusates were adjusted to 300 mosM and randomly infused at 200 ml/h. L-Phenylalanine enhanced acid-induced bicarbonate and protein outputs, as did pH 2.0 BSA digests. At pH 3.5, only acid-induced protein output was augmented by BSA digests. In additional studies, undigested or digested BSA at pH 7.0 was infused with secretin (82 pmol.kg-1.h-1). Only digested BSA enhanced secretin-induced pancreatic secretion. We conclude that there is an important, albeit complex, interaction between the intestinal acid stimulus and the protein digest stimulus on pancreatic secretion.
Minute rhythm of electrical spike bursts of the small intestine in different species
Authors: Fleckenstein P. , Bueno L. , Fioramonti J. , Ruckebusch Y.
Published: December 2017

Electrical activity of propagating spike bursts recurring at minute intervals was recorded from the small intestine by chronically implanted electrodes in the rabbit, cat, dog, sheep, and pig. This "minute rhythm" has been recorded previously from the intact human small intestine. It occurs in the jejunum with a period duration of 0.5-2.0 min in all species examined. The minute rhythm was accompanied by pressure waves propagating over a short distance, and the activity was most prominent before the onset of phase III of the myoelectric complex. The minute rhythm was activated by the infusion of saline in the jejunum, and it may possibly reflect a normal mechanism for the transport of fluid content.
Vasoactive agents and splanchnic oxygen uptake
Authors: Kvietys P. R. , Granger D. N.
Published: December 2017

Many vasoactive agents are known to alter oxygen uptake by splanchnic organs. Data from the literature indicate that, in general, vasodilators increase, whereas vasoconstrictors decrease oxygen uptake. We compare and contrast the effects of vasoactive agents on oxygen uptake observed in vivo, under constant-flow and free-flow conditions, to those observed in vitro. The discrepancies between the in vivo and in vitro data are discussed relative to the effects of vasoactive agents on blood flow, intraorgan blood flow distribution, the countercurrent exchange of oxygen, capillary exchange capacity, and oxidative metabolism. Changes in blood flow, oxidative metabolism, and capillary density appear to be the major mechanisms by which vasoactive agents alter splanchnic oxygen uptake in vivo. Experimental designs are proposed that may help minimize inconsistencies in the data in future studies.
Simulation and analysis of hepatic indicator dilution curves
Authors: Luxon B. A. , Forker E. L.
Published: December 2017

The "multiple-indicator dilution method" of measuring hepatic transport kinetics is subjected to simulation analysis. The objective is to examine the errors that may arise from treating the nonexchanging vasculature as a simple delay and to study the information content of simulated venous outflow curves. We find that the method cannot be counted on to provide consistently reliable estimates of either the transport rate constants or the sinusoidal volume. Estimates of the rate constant for irreversible solute removal from within liver cells are especially likely to be wrong. We suggest an alternative formulation of the governing differential equations that can substantially improve the estimates of the uptake parameter. These estimates may otherwise be subject to large systematic errors. Finally we discuss why the steady-state extraction fraction computed from the fitted parameters should be checked against a model-independent estimate obtained directly from the areas under the outflow curves. A method for making this comparison is at hand and should prove useful as a minimum criterion of internal consistency in animal experiments.
Effect of xenopsin on blood flow, hormone release, and acid secretion
Authors: Zinner M. J. , Kasher F. , Modlin I. M. , Jaffe B. M.
Published: December 2017

We investigated the effects of the neurotensin analogue xenopsin on regional blood flow, central hemodynamics, and stimulated acid secretion in awake conscious dogs. Organ blood flow, estimated using the radioactive microsphere technique, was significantly increased during the xenopsin infusion to the adrenals, pancreas, and ileum. There was no change in mean arterial pressure or cardiac output (measured by thermodilution). Along with changes in blood flow, there was a significant increase in the hormone output from the pancreas. These included rises in plasma pancreatic polypeptide, insulin, and glucagon. There also was a rise in plasma cortisol levels during the infusion. Substance P levels rose slowly but significantly during the xenospin infusion. There was no change in plasma gastrin levels. Xenopsin produced a significant inhibition of tetragastrin-stimulated gastric acid output. Thus, xenopsin appears to have region-specific influence on blood flow that correlates with region-specific hormonal secretion. In addition, xenopsin, like its mammalian analogue neurotensin, is an inhibitor of stimulated gastric acid secretion. A mammalian xenopsinlike peptide may well be involved in the modulation of gastrointestinal function.
Pepsinogen release from isolated gastric glands
Authors: Koelz H. R. , Hersey S. J. , Sachs G. , Chew C. S.
Published: December 2017

The in vitro release of pepsinogen was studied using a preparation of isolated gastric glands from rabbits. The pepsinogen content of the glands was estimated to be about 700 U/mg dry wt. Spontaneous release of pepsinogen was found to be less than 1% of the total per hour and relatively constant for at least 2 h. Pepsinogen release was stimulated in a dose-dependent manner by both carbachol and isoproterenol. The cholinergic and beta-adrenergic stimulation was selectively inhibited by atropine and propranolol, respectively. Removal of external calcium inhibited the responses to both isoproterenol (partially) and carbachol (completely). Several agents, including histamine, prostaglandin (E2), and synthetic secretin, were found not to stimulate pepsinogen release. However, a crude secretin preparation (Boots) was found to produce significant stimulation. Dibutyryl cAMP increased pepsinogen release in a dose-dependent manner. Isoproterenol was found to increase the cAMP content of gastric glands and to stimulate adenylyl cyclase activity in homogenates. The beta-adrenergic stimulation of adenylyl cyclase was found to be selective for a population of gastric cells that was relatively depleted of parietal cells and distinct from the histamine-stimulated adenylyl cyclase activity. The results indicate that pepsinogen secretion by the gastric chief cell is regulated, in part, by separate cholinergic and beta-adrenergic mechanisms and that both calcium and cAMP play a role in this regulation.
Site of thyroxine-evoked decrease of jejunal lactase in the rat
Authors: Boyle J. T. , Kelly K. , Krulich L. , Koldovsky O.
Published: December 2017

Localization of thyroid-mediated decrease of lactase activity along the villus-crypt unit in adult rat jejunum was studied 24 and 48 h after first injection of L-thyroxine (200 micrograms/100 g body wt) every 24 h. [3H]thymidine was also given at time of first thyroxine injection. Serum thyroid-stimulating hormone, food intake, and body weight were significantly decreased within 24 h. Total jejunal protein and villus-crypt height were unchanged during the time period studied. Lactase activity (expressed both as per tissue protein and per intestinal segment) was significantly decreased in jejunum and midjejunum within 24 h. Serial sectioning of the jejunal villus-crypt unit in a cryostat showed that the site of decrease in lactase activity at 24 h was in the apical villus and by 48 h extended along the entire height of the villus. Epithelial cell migration measured both by histoautoradiography and scintillation counting of [3H]thymidine in cryostat sections revealed no difference between control and thyroid-treated animals at both 24 and 48 h. The decrease in lactase activity at 24 h was in advance of the leading edge of radioactivity, indicating that the thyroid-evoked response occurred in mature enterocytes already on the villus.
Effect of neurotensin on mechanical and intracellular electrical activity of the canine stomach
Authors: Sanders K. M. , Schmalz P. , Szurszewski J. H.
Published: December 2017

Intracellular microelectrode and standard organ bath techniques were used to study in vitro the effects of neurotensin on the electrical and mechanical activities of canine antral circular smooth muscle. Neurotensin reduced or abolished spontaneous contractions. Muscarinic and adrenergic antagonists and tetrodotoxin did not block the effects of neurotensin, suggesting that the action of neurotensin was due to a direct action on the smooth muscle cell. Although the inhibitory effect of norepinephrine and neurotensin was similar, the effect of neurotensin did not appear to occur by an adrenergic mechanism because alpha- and beta-receptor blockade had no effect. Neurotensin also reduced or abolished contractions stimulated by pentagastrin and acetylcholine. The inhibitory effect of neurotensin on spontaneous acetylcholine- and pentagastrin-stimulated contractions was associated with a decrease in the amplitude and duration of the plateau potential of the gastric action potential. The data suggest that modulation of antral contractions by neurotensin occurs through a voltage-dependent mechanism that operates during the plateau potential.
Action of somatostatin on stomach, pancreas, gastric mucosal blood flow, and hormones
Authors: Lin T. M. , Evans D. C. , Shaar C. J. , Root M. A.
Published: December 2017

In dogs gastric secretion induced by tetragastrin and pancreatic secretion induced by secretin and/or cholecystokinin were inhibited by somatostatin at doses of 0.06-1 microgram X kg-1 X h-1 and 0.06-1 microgram X kg-1 X 0.5 h-1, respectively. Inhibition was a linear function of the logarithm of dose. Basal and 2-deoxy-D-glucose-induced gastric acid secretion was also significantly inhibited by low doses of somatostatin. Results in this study differ from those reported previously by clarifying the action of somatostatin as follows. 1) The inhibitory effect of somatostatin on pancreatic protein secretion was significantly greater than that on water and bicarbonate production. Somatostatin was more effective on cholecystokinin- than secretin-induced pancreatic secretion. 2) Although gastric mucosal blood flow (MBF) was affected by somatostatin, the reduction of MBF was not the primary mechanism responsible for its inhibitory action. 3) The low doses of somatostatin used in this study significantly inhibited gastric and pancreatic secretion without affecting the basal plasma concentrations of insulin, glucagon, growth hormone, gastrin, or secretin in the dogs, suggesting that the inhibitory action was not mediated by changes or reduction in plasma concentration of these hormones.
Microelectrode studies of Necturus antral mucosa: electrical potentials and resistances
Authors: Grady T. P. , Cheung L. Y.
Published: December 2017

Intracellular microelectrode techniques were applied to Necturus antral mucosa. Stable intracellular impalements were obtained with 15-50 M omega microelectrodes filled with 3M KCl. It was possible to change rapidly the mucosal bathing solution while maintaining the microelectrode in the cell. With these techniques, we were able to measure the electrical potentials and resistances of the cell membranes and the shunt pathway. The transepithelial potential was -4.9 +/- 1.3 mV, serosal solution reference. Apical cell membrane potential was -43.9 +/- 0.6 mV, cell negative to the mucosal solution. Basolateral cell membrane potential was -48.8 +/- 1.3 mV, cell negative to serosal solution. Transepithelial resistance was 427 +/- 66 omega . cm2. The ratio of apical to basolateral membrane resistances was 3.4 +/- 0.3. The electrical resistances of the transcellular and paracellular pathway were determined by the measurement of the total transepithelial resistance and the ratio of apical to basolateral cell membrane resistances before and after blocking apical membrane sodium permeability with amiloride. The resistances of the apical cell membrane, basolateral cell membrane, and the shunt were 2,203 +/- 585, 1,296 +/- 384, and 604 +/- 81 omega . cm2, respectively (mean +/- SE). Calculations from these measurements indicate that the shunt contribution to transepithelial conductance was approximately 85%.
Uptake of monohydric alcohols by liver: demonstration of a shared enzymic space
Authors: Goresky C. A. , Gordon E. R. , Bach G. G.
Published: December 2017

Multiple-indicator dilution studies of the hepatic uptake of straight-chain C1-C5 monohydric alcohols were carried out in anesthetized dogs, with either no preceding or saturating infusions of ethanol, and at different steady-state levels for the C2 experiments. Labeled red cells were utilized as a vascular reference, and labeled water was used as a second reference entering liver cells. Kinetic analysis of the data provided estimates of both an uptake rate constant and the space of distribution available to label. From the decrease in the uptake rate constant for labeled ethanol with bulk concentration, we calculated a maximal removal rate of 0.025 mumol X s-1 X (ml liver water)-1 and a Michaelis constant (Km) of 0.32 mM. Especially for the labeled C3-C5 alcohols, a space in excess of that available to water was found, and the bulk of this was dissipated by ethanol infusion. The increment, the "shared enzymic space", which varies with enzymic concentration and inversely with Km, was used to calculate Km values for the other alcohols.
Effect of lanthanum on pancreatic protein synthesis in streptozotocin-diabetic rats
Authors: Korc M.
Published: December 2017

The role of extracellular Ca2+ in mediating the stimulatory effect of cholecystokinin octapeptide (CCK8) on [3H]phenylalanine incorporation into protein was studied in isolated pancreatic acini from streptozotocin-diabetic rats. The stimulatory effect of CCK8 (10(-10) M) on [3H]phenylalanine incorporation was completely abolished by preincubating acini with either 10(-4) M lanthanum or 10(-3) M manganese. At these concentrations neither compound altered the basal rate of amino acid incorporation, and both compounds inhibited CCK-mediated Ca2+ influx without affecting either basal or CCK-mediated 45Ca2+ efflux. Lanthanum (10(-4) M) also blocked the stimulatory effect of the cholinergic analogue carbachol (10(-5) M) on amino acid incorporation but did not alter the stimulatory effect of insulin (1.67 x 10(-8) M). Vasoactive intestinal polypeptide and 12-O-tetradecanoyl-phorbol-13-acetate failed to increase the incorporation of [3H]phenylalanine into acinar protein. These findings suggest that CCK and other pancreatic secretagogues that act via Ca2+ enhance protein synthesis by increasing cell membrane permeability to Ca2+ and provide additional evidence that this may be an important mechanism by which CCK regulates pancreatic exocrine function.
A role for basolateral anion exchange in active jejunal absorption of HCO-3
Authors: White J. F. , Imon M. A.
Published: December 2017

Isolated short-circuited segments of jejunum from Amphiuma absorbed HCO-3 at a rate determined by the anion composition of the bathing media. The rate of HCO-3 absorption (JHCO-3) measured by pH-stat was high when the major anion was Cl-, Br-, I-, or SO2-(4) but was lower when gluconate or benzene sulfonate (SO-3) was the anion. The disulfonic stilbenes SITS, DIDS, and DNDS at 1 mM reduced JHCO-3 and short-circuit current when added to the serosal bathing medium. Inhibition by SITS was comparable whether Cl-, Br-, or SO2-(4) was the major anion, and SITS produced a small inhibition of JHCO-3 in gluconate-based media and no effect in benzene SO3-based media. Under conditions in which tissue conductance was low SITS lowered tissue conductance further. In Cl- media SITS reduced short-circuit current consistent with inhibition of Cl- absorption as well as HCO-3 absorption. Inhibition of the Cl- current by DIDS was not reversed by washout, although the inhibition of JHCO-3 was reversed. The rate of HCO-3 absorption in gluconate media could be increased by serosal addition of Cl-, Br-, or I-. It is concluded that the process that results in net jejunal HCO-3 absorption entails anion-HCO-3 exchange at the basolateral membrane and is distinct from the basolateral Cl(-)-HCO-3 exchange process involved in Cl- absorption.
Membrane properties and innervation of smooth muscle cells in Hirschsprung's disease
Authors: Kubota M. , Ito Y. , Ikeda K.
Published: December 2017

Mechanical and membrane properties of smooth muscle cells and/or neuroeffector transmission in the aganglionic segment of the large intestine (Hirschsprung's disease) were compared with findings in the ganglionic segment. Tension-recording, microelectrode, and double sucrose gap methods were used. There was no difference in resting membrane potential of the longitudinal or circular muscle cell in these two segments, which were obtained at biopsy in Japanese children. In the ganglionic preparations, generations of regular prepotentials, with or without the spike, correlated well to the rhythmic contractions. However, in the aganglionic segment, irregular spike and contraction only were observed. In the circular or longitudinal muscle of the ganglionic segments, field stimulations evoked inhibitory junction potentials, excitatory junction potentials, or both and triggered initial relaxation and then a contraction of the tissue. In the aganglionic segment, however, field stimulation evoked only excitatory junction potentials followed by contraction. These results indicate that, in cases of Hirschsprung's disease, there may be a deficiency in the nonadrenergic inhibitory pathways. This is the first evidence for a lack of spasticity in muscle from the aganglionic segment of the large intestine obtained from children with Hirschsprung's disease.
Jejunum is more important than terminal ileum for taurocholate absorption in rats
Authors: McClintock C. , Shiau Y. F.
Published: December 2017

The terminal ileum, with its active transport system, is considered the major site of bile salt absorption. However, earlier studies used bile salt concentrations below physiological levels and may not apply in vivo. Analysis of these studies shows that ileal active transport cannot account for total bile salt recovery. To reevaluate bile salt absorption in rats, we used four preparations and physiological bile salt concentrations. Studies with intestinal sacs showed that, above critical micellar concentration, uptake of taurocholate (TC) was equal in both jejunum and ileum and linear with respect to concentration. A similar pattern was observed in studies of mucosal-to-serosal TC transport using a flux chamber. In vivo studies in anesthetized rats showed approximately 30% of TC absorbed from proximal jejunum and appearing in bile when the bolus had traversed only half the intestine. In unanesthetized fed rats, 60% of TC appeared in bile before the bolus reached distal ileum. Because luminal concentrations of TC are highest proximally, passive absorption by the proximal intestine is mainly responsible for conserving TC within the enterohepatic circulation. Ileal active transport is more efficient at low concentrations and absorbs the TC remaining after proximal absorption.
Mild irritants prevent gastric necrosis through "adaptive cytoprotection" mediated by prostaglandins
Authors: Robert A. , Nezamis J. E. , Lancaster C. , Davis J. P. , Field S. O. , Hanchar A. J.
Published: December 2017

Several prostaglandins (PG) were found earlier to be cytoprotective for the stomach and the intestine. We now report that mild irritants, given intragastrically, are also cytoprotective by stimulating the release of PG by the stomach. Several "mild irritants," 10-20% ethanol, 0.2-0.35 M HCl, 0.05-0.075 M NaOH, 2-4% NaCl, and water at 70 degrees C, were given orally to fasted rats. Fifteen minutes later, one of the following necrotizing agents was administered orally: 100% ethanol, 0.6 M HCl, 0.2 M NaOH, 25% NaCl solution, and boiling water. One hour later, the stomachs were removed and necrotic lesions graded. The mild irritants inhibited the necrotic lesions dose dependently. After a single treatment, protection lasted 1 h; repeated administrations maintained cytoprotection for as long as the mild irritants were being given. Indomethacin, an inhibitor of PG synthesis, abolished cytoprotection by mild irritants. After oral administration of NaOH at cytoprotective concentrations (0.01-0.1 M), the amounts of PGE2, PGF2 alpha, and thromboxane B2 formed by the gastric mucosa increased steadily up to threefold. The protection elicited by mild irritants is called "adaptive cytoprotection." The increased synthesis of PG may represent a physiological, natural defense mechanism that may be necessary to maintain cellular integrity of the gastrointestinal mucosa, in spite of the hostile environment caused by luminal contents.
Does substance P comediate with acetylcholine in nerves of opossum esophageal muscularis mucosa?
Authors: Domoto T. , Jury J. , Berezin I. , Fox J. E. , Daniel E. E.
Published: December 2017

In opossum esophagus the highest density of varicose substance P-like immunoreactive deposits was in the muscularis mucosa, and this muscle layer, which is thick and prominent, was the most sensitive in contracting to exogenous substance P. On field stimulation, a tetrodotoxin-sensitive biphasic contraction was produced; an initial phasic component was followed after cessation of stimulation by a prolonged tonic component. This contractile response was unaffected by guanethidine or antagonists to several nerve mediators and to histamine and serotonin antagonists. Each component showed a different frequency dependence. The phasic component was abolished by atropine and potentiated by physostigmine; the tonic component was reduced or abolished after carbachol or physostigmine and potentiated by atropine. The tonic component was inhibited after substance P tachyphylaxis or by the substance P antagonist [D-Pro2, D-Trp7,9]substance P. On electron microscopic examination, the majority of nerve varicosities contained a mixture of small agranular and large granular vesicles. We postulate that acetylcholine and substance P may coexist in and be coreleased from nerves of this muscle and that the acetylcholine release occurs first, causing an initial phasic response and delaying and diminishing the release of substance P. The two mediators cause muscle contraction by actions on independent receptors.
Bimodal regulation of pancreatic exocrine function in vitro by somatostatin-28
Authors: Esteve J. P. , Vaysse N. , Susini C. , Kunsch J. M. , Fourmy D. , Pradayrol L. , Wunsch E. , Moroder L. , Ribet A.
Published: December 2017

The action of natural and synthetic somatostatin-(1--28), [Nle8]somatostatin-(1--28), somatostatin-(15--28), and somatostatin-(1--14) was examined in dispersed acini from guinea pig pancreas. At high concentrations, the 28-amino acid form of somatostatin increased amylase release, outflux of 45Ca, cellular cGMP, and to a lesser extent cellular cAMP. The increase in amylase release was suppressed by dibutyryl cGMP but was not modified by theophylline or atropine. Binding of 125I-labeled [Thr28, Nle31] cholecystokinin-(25--33) was inhibited by [Nle8]somatostatin-(1--28). These effects required the entire 28-amino acid peptide and appeared to result from occupation of cholecystokinin receptors. It is postulated that they involve interactions between the C-terminal and the N-terminal sequences of the molecule with the participation of the amino acid in position 8. At low concentrations, natural and synthetic forms of somatostatin-(1--28) and somatostatin-(15--28) inhibited secretin- and vasoactive intestinal peptide (VIP)-stimulated increases in cellular cAMP concentration. No difference was found between the potency of somatostatin peptides, indicating that the tetradecapeptide somatostatin-(15--28) is sufficient to exert an inhibitory action on secretin- and VIP-stimulated cellular cAMP concentration. By contrast, the somatostatin fragment S-(1--14) was inactive on pancreatic cellular function.
Stimulation of motilin release by bombesin in dogs
Authors: Poitras P. , Tasse D. , Laprise P.
Published: December 2017

Bombesin (BBS) was infused in conscious fasting dogs to document its effects on the release of motilin in the blood and on intestinal motility. When BBS was infused for 3 h (0.125 and 0.5 microgram X kg-1 X h-1), a specific pattern of myoelectric activity was induced: 1) the pacesetter potentials were increased in frequency but decreased in amplitude; 2) a moderate spike activity (weak phase II) was superimposed on this disorganized pacesetter activity, and activity fronts were abolished despite elevated motilin levels. A second experiment was performed in which motilin levels during BBS administration for a selected period of an interdigestive myoelectric complex (IDMC) could be compared with those obtained at a similar period of a preceding IDMC in which a saline solution had been infused. The motilin blood levels measured during BBS administration (0.25, 0.5, 1.0, and 2.0 micrograms X kg-1 X h-1 for 20 min each stepwise) were significantly higher than those obtained with saline. The administration of BBS synchronized with the IDMC was necessary to document its effect on motilin release, because when BBS was infused at an unknown period of the IDMC no rise of motilin levels over basal could be detected. Because of its contradictory effects on the release of motilin (stimulation of motilin release) and on the IDMC (inhibition of motilin effect), a physiological role of BBS as an endocrine regulator of motilin release is questionable. On the other hand, the possibility that BBS controls motilin release in a paracrine or neurocrine role cannot be excluded.
Contraction and [3H]QNB binding in collagenase isolated fundic smooth muscle cells
Authors: Seidel E. R. , Johnson L. R.
Published: December 2017

Smooth muscle cells from the guinea pig gastric fundus were isolated by successive collagenase digestions. Tritiated quinuclidinyl benzilate [( 3H]QNB) was used to study the binding characteristics of the muscarinic cholinergic receptors on these cells. Each cell bound 8.3 X 10(-19) mol of QNB, and a concentration of QNB of 0.19 nM was required to label one-half of the binding sites. This suggests a concentration of about 500,000 muscarinic cholinergic receptors per smooth muscle cell. The muscarinic cholinergic receptor antagonists atropine and scopolamine inhibited QNB binding with a 50% inhibiting concentration (IC50) in the nanomolar range, whereas the agonists acetylcholine (ACh), oxotremorine, and carbamylcholine had IC50S in the micromolar range. Hill coefficients (nH) for antagonists approached unity, but agonists displayed fractional nH. Exposure of cells to cholinergic muscarinic agonists resulted in dose-dependent decreases in cell length. The concentration of agonist required to induce half-maximal contractions (ED50) was 8.3 X 10(-12) M for ACh and 6.3 X 10(-13) M for oxotremorine. Atropine (10(-9) M) decreased the sensitivity to ACh, increasing the ED50 for ACh-induced contractions to 1.2 X 10(-10) M. These results suggest the existence of muscarinic receptor heterogeneity for cholinergic agonists but not for antagonists.
Ischemia-induced vascular changes: role of xanthine oxidase and hydroxyl radicals
Authors: Parks D. A. , Granger D. N.
Published: December 2017

The results of previous studies indicate that oxygen-derived free radicals are responsible for the increased vascular permeability produced by 1 h of intestinal ischemia. The aims of this study were 1) to test the hypothesis that the enzyme xanthine oxidase is the source of oxygen radicals in the ischemic bowel and 2) to assess the role of the hydroxyl radical in the ischemia-induced vascular injury. The capillary osmotic reflection coefficient was estimated from lymphatic protein flux data in the cat ileum for the following conditions: ischemia, ischemia plus pretreatment with allopurinol (a xanthine oxidase inhibitor), and ischemia plus pretreatment with dimethyl sulfoxide (a hydroxyl radical scavenger). The increased vascular permeability produced by ischemia was largely prevented by pretreatment with either allopurinol or dimethyl sulfoxide. These findings support the hypothesis that xanthine oxidase is the source of oxygen radicals produced during ischemia. The results also indicate that hydroxyl radicals, derived from the superoxide anion, are primarily responsible for the vascular injury associated with intestinal ischemia.
Some parameters of descending inhibition during colonic propulsion
Authors: Mancinelli R. , Marzio L. , Pescatori M. , Bertuzzi A. , Salinari S. , Serrao F. , Vulpio C. , Emanuele T.
Published: December 2017

Isolated segments of rabbit distal colon were stimulated by distension of intraluminal balloons, with the aim of investigating the electrophysiological pattern of descending inhibition (DI) during the peristaltic reflex. Incidence, duration, and latency of DI were studied by varying the parameters of stimulation. A linear correlation was found between stimulus duration and DI duration for stimuli up to 10 s long. DI duration increased with the distance of the recording site from the stimulus up to 3 cm. A more complex relation was found between balloon volume and DI duration. Propagation velocity decreased with the distance from the stimulus. The relation between ascending excitation and DI was also studied: ascending excitation could always be suppressed by DI. DI was examined after addition of anticholinergics, ganglionic blocking agents, and tetrodotoxin to the organ bath. The results show that DI parameters are partially related to the stimulus characteristics and that propagation of DI is neurally mediated through nonadrenergic inhibitory nerves.
Effects of cholecystokinin and secretin on intestinal structure and function
Authors: Fine H. , Levine G. M. , Shiau Y. F.
Published: December 2017

Cholecystokinin and secretin are believed to be trophic gastrointestinal hormones. Studies were designed to determine whether these hormones exert their effect through stimulation of endogenous secretion. First, four groups of parenterally nourished rats underwent bypass of the proximal two-thirds of the intestine. One group received secretin, another cholecystokinin octapeptide (CCK-OP), another CCK-OP plus secretin, while the fourth group served as control. After 1 wk, animals were killed; pancreas and segments of intestine were removed. First, mucosal weight, protein content, and fatty acid esterification activity were affected only in intestine in continuity with endogenous secretions after hormone administration. Second, the effects of these hormones were tested in chow-fed rats. The hormone-treated group, despite pancreatic hyperplasia, had similar indexes of intestinal mass compared with pair-fed controls. We conclude that CCK-OP and secretin mediate their trophic effects on the small intestine indirectly, probably through stimulation of pancreatic secretion. In addition, the effects of luminal nutrients have complex interactions with these hormones.
Restricted transport of cationic macromolecules across intestinal capillaries
Authors: Perry M. A. , Benoit J. N. , Kvietys P. R. , Granger D. N.
Published: December 2017

The charge-selective properties of intestinal capillaries were investigated by measuring steady-state lymph-to-plasma concentration ratios (L/P) of endogenous and exogenous macromolecules of comparable molecular size but different charge. The steady-state L/P values for endogenous lactate dehydrogenase isoenzymes (LD1-LD5) decreased with increasing isoelectric point. The osmotic reflection coefficient for LD1, the most negative isoenzyme studied, was 0.71 +/- 0.01; that for the most positive isoenzyme (LD5) was 0.95 +/- 0.01. The steady-state L/P for an exogenous molecule, neutral dextran, was 0.51 +/- 0.04; the L/P for the positively charged dextran of similar size was 0.25 +/- 0.04. The results indicate that intestinal capillaries behave as a positively charged barrier that reduces blood-lymph exchange of cationic macromolecules and enhances the exchange of anionic molecules.
Cl- requirement of acid secretion in isolated gastric glands
Authors: Malinowska D. H. , Cuppoletti J. , Sachs G.
Published: December 2017

The dependence of acid formation, as measured by aminopyrine (AP) accumulation, on medium and intracellular Cl- was investigated in resting (10(-4) M cimetidine) and stimulated (10(-3) M dibutyryl cAMP) gastric glands isolated from the rabbit stomach. Intracellular Cl- concentrations (Cli-) were measured by the steady-state distribution of 36Cl-. In Cl- -free conditions AP accumulation was absent. Medium Cl- induced AP accumulation (AP ratio = 125) in stimulated glands with a K0.5 of 10.4 +/- 1.1 mM, equivalent to 18.0 +/- 1.2 mM Cli-, and had a small effect on resting glands (AP ratio = 6). With normal Nai+ and Ki+ maintained, similar results were obtained in stimulated glands treated with 10(-5) M amphotericin (ampho) and 10(-4) M ouabain (ouab), where the basal-lateral membrane was confirmed to be short-circuited with respect to Cl- pathways, i.e., medium Cl- and Cli- were equal. The K0.5 for Cl-i was 17.5 +/- 2.5 mM. In resting glands treated with ampho and ouab, AP accumulation increased linearly (no saturation was observed) with increasing Cl- (AP ratio = 35). These results suggest that stimulation activates a Cl- component in the secretory membrane and not in the basal-lateral membrane of the parietal cell. The K+ requirement of AP accumulation at a physiological Cl-i of 60 mM was also investigated in ampho- and ouab-treated glands. On stimulation the K0.5 for Ki+ decreased from 19.5 to 12 mM, coupled with a large increase in AP accumulation, indicating that stimulation also activates a K+ component in the secretory membrane.(ABSTRACT TRUNCATED AT 250 WORDS)