bluuebunny/crossref_metadata_2025 huggingface dataset:
Lysolecithin-lipid interactions in disruption of the canine gastric mucosal barrier
Authors: Duane W. C. , McHale A. P. , Sievert C. E.
Published: December 2017

Lysolecithin has been implicated in the pathogenesis of gastric ulcer and reflux gastritis. By use of canine Heidenhain pouches, we examined effects of lysolecithin on the gastric mucosal barrier both at neutral (PO4 buffer, pH 7) and acidic (0.15 M HCl) pH with respect to interaction of lysolecithin with membrane lipids. At both pH values, 2 mM lysolecithin significantly increased forward diffusion of Na+ and backdiffusion of H+. Both solutions also caused significant efflux of membrane phospholipid and cholesterol. Saturation of neutral and acidic lysolecithin solutions with either lecithin or cholesterol significantly diminished or completely prevented disruption of the barrier to H+ backdiffusion and Na+ forward diffusion. In agreement with other reports, we also demonstrated formation of soluble lysolecithin-lecithin mixed micelles but formation of insoluble lysolecithin-cholesterol complexes. Finally, by use of [3H]polyethylene glycol and [14C]lysolecithin, we demonstrated more rapid mucosal uptake of lysolecithin at acidic than at neutral pH for any given experimental condition. Specifically, mean mucosal uptake of lysolecithin from acidic solutions saturated with lecithin (which did not disrupt the gastric mucosal barrier) was greater than uptake from neutral solutions without added lipid (which did disrupt the barrier). These studies suggest that lysolecithin-lipid interactions play an important role in lysolecithin-induced injury to the gastric mucosa. The most important of these interactions appears to occur in luminal lysolecithin micelles rather than within mucosal membranes.
Pancreatic tissue oxygenation during secretory stimulation
Authors: Harper S. L. , Pitts V. H. , Granger D. N. , Kvietys P. R.
Published: December 2017

Pancreatic acinar tissue O2 tension (PO2) was measured in anesthetized rats using recessed-tip microelectrodes (tip diam 1-2 micron). Pancreatic blood flow was measured using radioactive microspheres. Volume rate of pancreatic secretion, as well as protein concentration, was also measured. Average resting PO2 was 24.8 +/- 1.6 mmHg, with relatively little variation evident within a given pancreas. Bolus intravenous infusion of cholecystokinin octapeptide (CCK-OP, 4 micrograms X kg body wt-1) induced a reduction in tissue PO2 and profoundly increased protein output, while not directly affecting pancreatic blood flow. By contrast, secretin infusion (1.0 CU X kg body wt-1 iv bolus) affected neither tissue PO2 nor blood flow, although secretory rate increased by nearly sevenfold. This difference in PO2 response to the two compounds is interpreted in light of the fact that CCK-OP primarily stimulates acinar cell function, while secretin preferentially activates secretory epithelium. Pancreatic PO2 was found to be linearly related to resting blood flow at flows above 44 ml X min-1 X 100 g-1. No regional differences in blood flow were found in the head, body, and tail of the pancreas.
Active potassium secretion by rabbit proximal colon
Authors: Sullivan S. K. , Smith P. L.
Published: December 2017

Fluxes of K from mucosa to serosa or serosa to mucosa have been examined in stripped preparations of rabbit proximal and distal colon in vitro under short-circuit conditions in Ussing chambers. Results from these studies demonstrate that steady-state radioisotopic fluxes of K are achieved after 90 min and remain constant for at least 2 h. Determination of the K concentration dependence of the serosal-to-mucosal K flux revealed that this flux contains both saturable and nonsaturable components. Addition of ouabain (0.1 mM) abolished the saturable component of the serosal-to-mucosal K flux. The mucosal-to-serosal K flux is a linear function of K concentration between 1 and 20 mM under basal conditions. In paired tissues, serosal-to-mucosal K flux is always greater than mucosal-to-serosal flux under basal conditions resulting in net K secretion. However, addition of barium (2 mM) to the mucosal or serosal bathing solution had no significant effect on either unidirectional or net K fluxes. In addition, mucosal bumetanide (0.1 mM) or removal of Cl from both bathing solutions had no significant effect on unidirectional or net K fluxes. In rabbit distal colon, Cl removal from the bathing solutions significantly reduced serosal-to-mucosal K flux, resulting in net K absorption. These results indicate that rabbit proximal colon like rabbit distal colon actively secretes K. However, unlike distal colon the proximal colon does not possess an active K uptake mechanism at the apical cell membrane.(ABSTRACT TRUNCATED AT 250 WORDS)
Na+-H+ and Cl(-)-OH-(HCO3-) exchange in gastric glands
Authors: Paradiso A. M. , Negulescu P. A. , Machen T. E.
Published: December 2017

The pH-sensitive, fluorescent, cytoplasmic-trapped dye 2,7-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF) has been used to measure intracellular (pHi) and pH electrode to measure extracellular pH (pHo) in suspensions of gastric glands isolated from rabbit stomachs. The fluorescence of BCECF-loaded glands was calibrated in terms of pHi by equilibrating pHo and pHi using ionophores or digitonin and titrating pHo to different values. An APPENDIX is included that covers details of dye calibration and interpretation of fluorescence signals. Glands incubated in NaCl Ringer solution had pHi 7.11. Na+-free Ringer solution caused pHi to decrease reversibly to 6.80. Na+-dependent alkalinization of pHi followed a similar time course to the acidification of pHo. These changes were blocked by 1 mM amiloride. When gland cells were acidified (using two different techniques) realkalinization was completely Na+ dependent but was independent of the presence of Cl-; also, neither high extracellular K+ concentration ([K+]o) nor high [K+]o plus 10(-5) M valinomycin affected the rates of Na+-dependent alkalinization. A neutral Na+-H+ exchanger was implicated. Glands also exhibited Cl(-)-dependent changes of pHi that were blocked by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (2 X 10(-4) M). A Cl(-)-OH-(HCO3-) exchanger was indicated. Other studies showed that intracellular buffering capacity was approximately 45 mM (pH-1) and that the apparent proton conductance of gland cell membranes was small.
Relationships between duodenal motility and pancreatic secretion in fasted and fed dogs
Authors: Konturek S. J. , Thor P. J. , Bilski J. , Bielanski W. , Laskiewicz J.
Published: December 2017

A relationship between duodenal myoelectric or motor activity and exocrine pancreatic secretion as well as plasma gut hormone levels has been investigated in fasted dogs, fed dogs, and dogs that were stimulated with exogenous gut hormones. Pancreatic secretion showed typical periodicity in phase with the myoelectric or motor activity of the duodenum. Fasting pancreatic bicarbonate and protein secretion reached peaks during phase III of the interdigestive migrating motor complex (MMC) cycle that were significantly larger than nadir levels occurring during phase I of the cycle. These fasting bicarbonate and protein peaks reached, respectively, approximately 9 and 30% of the highest postprandial outputs and 4 and 14% of the maximal secretory capacity elicited by secretin or CCK. They were accompanied by a significant rise in plasma motilin, gastrin, and pancreatic polypeptide (PP), but only exogenous motilin given in physiological dose induced motility pattern and pancreatic secretion similar to those observed during phase III. Feeding interrupted both motor and secretory MMC cycle, increased the pancreatic secretion to approximately 40-60% of the maximal secretory capacity, and was accompanied by increments in plasma gastrin, cholecystokinin (CCK), secretin, and PP. None of these hormones applied alone in physiological dose was capable of reproducing the postprandial inhibition of MMC cycles. We conclude that the pancreatic secretion in fasted dogs fluctuates periodically in phase with duodenal motility, but the phase III peak secretory outputs represent only minute fractions of the maximal secretory capacity and can therefore be ignored in regular testing of pancreatic secretion.
Pentagastrin and gastric mucosal blood flow
Authors: Holm-Rutili L. , Berglindh T.
Published: December 2017

The effect of pentagastrin on mucosal microcirculation was studied in rats by use of intravital microscopy. The superficial mucosal vessels were videorecorded for off-line analysis of red cell velocities (VRBC) and vessel diameters, from which blood flow (QRBC) was calculated. Resting mucosal blood flow calculated from single microvascular flow data, and vessel distribution was 40 ml X min-1 X 100 g-1. Pentagastrin infused intravenously in a dose of 20 micrograms X kg-1 X h-1 resulted in submaximal acid secretion (approximately 60%) and a significant increase in QRBC by 47 +/- 14%. When given in a dose of 96 micrograms X kg-1 X h-1 iv, it resulted in maximal acid secretion and an increase in QRBC by 36 +/- 14%. In another series of experiments the results of QRBC measurements during infusion of pentagastrin (20 micrograms X kg-1 X h-1 iv) were compared with those of aminopyrine (AP) clearance or laser-Doppler flowmetry (LDF) in the same animals. Gastric mucosal blood flow determined by [14C]AP clearance increased by 309 +/- 115%, whereas QRBC increased by 34 +/- 11%. When determined by LDF, blood flow increased by 41 +/- 22%, a value similar to the increase in QRBC (50 +/- 19%). Thus, the percent increase in blood flow during pentagastrin infusion estimated by AP clearance was considerably higher than that observed by either direct microvascular measurements or by LDF.
Vagal nerve stimulation causes noncholinergic dilatation of gastric arterioles
Authors: Morishita T. , Guth P. H.
Published: December 2017

Vagal nerve stimulation causes prompt dilatation of gastric submucosal arterioles (the vessels that control gastric mucosal blood flow) in rats. In vivo microscopy was used to determine whether this direct vasodilator effect of vagal nerve stimulation on rat gastric submucosal arterioles is mediated by cholinergic fibers. Acetylcholine and atropine were topically applied to the submucosa. The distal end of the severed vagus nerve was electrically stimulated (8 V, 2 ms, 6 Hz, 20 s) subdiaphragmatically. Diameter changes of the submucosal arterioles were videotaped and measured with an image-splitting technique on playback of the videotapes. Acetylcholine, 10(-7) to 10(-5) M, dilated the arterioles dose dependently. Atropine prevented the acetylcholine-induced dilatation, 10(-5) M, nearly completely inhibiting the dilatation. Vagal nerve stimulation dilated the arterioles promptly, and this dilatation was not blocked by 10(-5) M atropine, a dose that blocked the acetylcholine-induced dilatation. These results indicate that vagal nerve stimulation causes atropine-resistant, noncholinergic dilatation of gastric submucosal arterioles in rats.
Blood flow limitation of stimulated gastric acid secretion in the rat
Authors: Leung F. W. , Kauffman G. L. , Washington J. , Scremin O. U. , Guth P. H.
Published: December 2017

Secretagogue-stimulated gastric acid output is reduced when gastric mucosal blood flow is below normal. We tested the hypothesis that the reduction in acid secretion associated with reduced mucosal blood flow was due to a decrease in the delivery of the secretagogue. Gastric acid output was determined by continuous gastric lavage with 0.15 M NaCl, and gastric corpus mucosal blood flow was measured by hydrogen gas clearance in anesthetized, pylorus-ligated rats before and during a period of hypovolemia-induced reduction in mucosal blood flow. A linear correlation between pentagastrin- and histamine-stimulated gastric acid output and gastric corpus mucosal blood flow during hypotension over a range of mucosal blood flow rates was found, and each was expressed as a percentage of the plateau values before hemorrhage. When the dose of pentagastrin was doubled or tripled, or when the stimulation of gastric acid secretion was vagus nerve stimulation, a stimulant of acid secretion that is independent of blood flow for secretatogue delivery, the reduction in gastric acid output by hypotension was not reversed. We conclude that stimulated gastric acid secretion during hemorrhagic hypotension is blood flow-limited and not related to inadequate delivery of secretagogue to parietal cells.
Processing of epidermal growth factor by suckling and adult rat intestinal cells
Authors: Rao R. K. , Thornburg W. , Korc M. , Matrisian L. M. , Magun B. E. , Koldovsky O.
Published: December 2017

Preparations of intestinal villus and crypt cells were isolated from jejunal segments of suckling (14-day-old) and adult (6- to 7-wk-old) rats. These cell preparations were incubated with 125I-labeled epidermal growth factor (EGF) at 37 degrees C to determine the extent of cellular processing of 125I-EGF in vitro. 125I-EGF bound specifically to both crypt and villus cells of suckling rats and was internalized and degraded to similar extents in both cell preparations. Analysis of the 125I radioactivity in the medium and cellular extract by gel filtration on Sephadex G-25 columns demonstrated the presence of [125I]iodotyrosine (24–31%) following 30 min of incubation. This degradation of EGF was accompanied by a loss in the capacity to bind to anti-EGF antibodies (34–52%) and A431 cells (28–48%). Binding, internalization, and processing of 125I-EGF by crypt cell preparations of adult rats was similar to that of suckling rats. In contrast, little degradation of 125I-EGF to iodotyrosine and loss of cell binding capability occurred following incubation with adult villus cells. However, a considerable loss in binding to anti-EGF antibody was detected (48%). The results indicate that isolated intestinal cells are capable of degrading 125I-EGF in vitro in a manner similar to that seen after oral feeding in vivo. They also indicate differences in the processing of 125I-EGF by isolated villus cells of adult compared with suckling rat.
Characterization of substance P effects on canine antral muscle
Authors: Mayer E. A. , van Deventer G. , Elashoff J. , Khawaja S. , Walsh J. H.
Published: December 2017

Synthetic substance P increased the frequency and amplitude of spontaneously occurring contractions of circular and longitudinal muscle strips from canine gastric antrum in vitro. In longitudinal muscle, ED50 values calculated for frequency and amplitude were 3.7 X 10(-9) M and 9.7 X 10(-7) M, respectively. The effect of substance P on frequency in both layers and on amplitude in the circular layer was myogenic and unrelated to receptors for acetylcholine, norepinephrine, serotonin, histamine, and enkephalins. In the longitudinal muscle the amplitude response was partially inhibited by tetrodotoxin, atropine, and hexamethonium. The effect on amplitude but not on frequency was dependent on extracellular calcium. When compared to other stimulants of antral muscle contraction, the biological potency of substance P was higher than that of acetylcholine but significantly lower than that of gastrin and bombesin. Two putative substance P antagonists ([D-Pro2,D-Phe7,D-Trp9]substance P and [D-Pro2, D-Trp7,9]substance P) did not block the response of longitudinal muscle to substance P. Only the chronotropic response to substance P showed consistent, prolonged desensitization. These findings suggest that the mechanisms mediating the response to substance P in the canine antrum are different from other reported tissues.
Choline evokes fluid secretion by perfused rat mandibular gland without desensitization
Authors: Murakami M. , Novak I. , Young J. A.
Published: December 2017

The secretomotor action of choline on salivary secretion has been studied in the isolated perfused mandibular gland of the rat. Choline made up in substituted Ringer solutions (Na concentrations of 40, 70, or 100 mM) was an effective secretomotor agonist in the concentration range of 1–100 mM and evoked secretory responses comparable with those of acetylcholine (0.05–1.0 microM) administered at similar Na concentrations. Continuous infusion of choline, in contrast to acetylcholine, did not lead to a fall off in the secretory response (desensitization or tachyphylaxis) until the choline concentration used exceeded approximately 80 mM. The secretomotor action of choline (46 mM) was blocked completely and reversibly by atropine (5 microM) but not by propranolol (2.5 microM) and phentolamine (2.5 microM) administered together. When acetylcholine (1.0 or 0.05 microM) was infused on a background of choline stimulation, a small additional secretory response was elicited whenever the choline stimulus was submaximal, and, regardless of the choline concentration employed, addition of acetylcholine always induced tachyphylaxis. The results suggest that choline and acetylcholine act on the same population of muscarinic receptors, but it is unclear why choline does not evoke tachyphylaxis. The response to choline allows us to exclude a number of the possible causes of tachyphylaxis that have previously been considered, so that an excessive buildup of cytosolic free Ca now remains as the most likely cause of the phenomenon.
Generation of phases I and II of migrating myoelectric complex in the dog
Authors: Lang I. M. , Sarna S. K. , Condon R. E.
Published: December 2017

The mechanisms of generation of most of the phases of the migrating myoelectric complex (MMC) are unclear. Except for phase III activity, this issue has not been investigated directly. We have qualitatively examined the relations between different phases of the MMC cycle in order to provide an objective basis for the formation of theories. Eight dogs of either sex were implanted with 10 bipolar electrodes distributed along the gastrointestinal tract. Myoelectric activity was recorded during the fasted state or after feeding until the return of the MMC cycle. The relations between phase I duration, phase II duration, phase III migration time, and phase III period were examined using simple linear-regression methods. We found that only phase I duration was highly correlated (r = 0.87, P less than 0.01) with phase III migration time and that only phase II duration was highly correlated (r = 0.90, P less than 0.01) with phase III period. In either the fed or fasted state, phase III activity that began in the midjejunum was accompanied concurrently with phase I activity of the duodenum and upper jejunum, where phase III activity had not occurred. Also, the position of phase III activity in the lower small intestine when phase I activity of the upper small intestine ended was 277 +/- 24 cm (83 +/- 5% of the small intestinal length) from the pylorus, and the coefficient of variation of this position was significantly smaller (P less than 0.01) than that of the other cycle variables.(ABSTRACT TRUNCATED AT 250 WORDS)
Postnatal development of protein absorption in conventional and germ-free mice
Authors: Heyman M. , Crain-Denoyelle A. M. , Corthier G. , Morgat J. L. , Desjeux J. F.
Published: December 2017

In the jejunal epithelium of adult animals, horseradish peroxidase (HRP) is transported via two functional pathways: a major route involving lysosomal degradation and a minor route allowing transport of the intact protein. The postnatal development of HRP absorption and the influence of conventional microflora were studied in vitro, using jejunal epithelium of conventional and germ-free suckling mice mounted in Ussing chambers. In conventional mice, tritiated peroxidase ([3H]HRP) transport from mucosa to serosa did not change with age except during days 3 and 4, when it increased fivefold. This increase was entirely due to the rise in intact HRP transport and was not related to a decrease in lysosomal cathepsin B and D activities. In germ-free mice, HRP transport developed similarly but decreased by 75% along both pathways. This reduced absorption was associated with lower cathepsin B and D activities. These results strengthen the existence of two transcellular pathways in nonimmunoglobulin protein absorption by the proximal gut with a limiting step situated before the lysosomal system, presumably at the brush-border membrane. Their development is not parallel and does not correlate with gut closure to immunoglobulin transfer.
Inhibitory effects of beta-adrenergic agonists on gastric acid secretion in dogs
Authors: Stevens M. H. , Thirlby R. C. , Richardson C. T. , Fredrickson M. A. , Unger R. H. , Feldman M.
Published: December 2017

We evaluated the effect of two beta-adrenergic agonists, isoproterenol (nonselective agonist) and terbutaline (selective beta 2-agonist), on gastric acid secretion stimulated by intravenous pentagastrin, bethanechol, or histamine in dogs with gastric fistulas. Intravenous infusion of isoproterenol or terbutaline inhibited pentagastrin-stimulated acid secretion to a significantly greater extent than they inhibited bethanechol- or histamine-stimulated acid secretion. For example, isoproterenol (12 micrograms X kg-1 X h-1) reduced mean pentagastrin-, bethanechol-, and histamine-stimulated acid output by 86, 63, and 14%, respectively. Percent inhibition of acid secretion with terbutaline (30 micrograms X kg-1 X h-1) averaged 60, 17, and 24% for pentagastrin, bethanechol, and histamine, respectively. Terbutaline also inhibited pentagastrin-stimulated acid secretion from vagally denervated fundic pouches in a dose-related manner. Plasma somatostatin-like immunoreactivity was significantly higher during infusion of terbutaline plus pentagastrin than during infusion of pentagastrin alone. However, an intravenous infusion of 0.3 microgram X kg-1 X h-1 somatostatin-14 had no effect on pentagastrin-stimulated acid secretion from the gastric fistula, even though this infusion increased plasma somatostatin-like immunoreactivity to the same extent as terbutaline plus pentagastrin infusion. Thus the amount of somatostatin released during terbutaline infusion was not sufficient to explain the inhibition of pentagastrin-stimulated acid secretion observed.
Hormonal regulation of postprandial induction of gastrointestinal ornithine decarboxylase activity
Authors: Seidel E. R.
Published: December 2017

The growth of gastrointestinal mucosa can be related to ingestion and digestion of diet, with fasting producing mucosal hypoplasia and hyperphagia producing mucosal hyperplasia. Experiments were designed to determine whether induction of polyamine metabolism following ingestion of a meal was related to mucosal growth. Activity of the enzyme ornithine decarboxylase (ODC) in both jejunum and ileum but not in duodenum was dependent on the presence of food in the gut; ODC activity was more than 200-fold greater in mucosa of fed rats than in fasted rats. Inhibition of ODC with difluoromethylornithine lead to mucosal atrophy in ileum but not in duodenum. Refeeding of fasted rats resulted in significant induction of ODC in duodenal, ileal, and colonic, but not fundic, mucosa. In addition, two hormones, epidermal growth factor and glucagon, were effective inducers of ileal ODC activity. Direct evidence for hormonal involvement in the postprandial rise in mucosal ODC activity was provided by experiments in rats that had undergone ileal bypass surgery. After refeeding of fasted rats mucosal ODC activity was induced in both ileum left in continuity and in the bypassed segment. Refeeding of elemental diets demonstrated that ingestion of carbohydrate alone was sufficient for maximal enzyme induction. Mixed amino acids or glyceryl trioleate were no more effective inducers than nonnutritive solutions of cellulose or saccharin. These data demonstrate that hormones which are released during ingestion and digestion of a meal are the stimuli for induction of mucosal polyamine metabolism, suggesting that food-induced mucosal growth is hormonally mediated.
Alteration of intracellular synthesis of surface membrane glycoproteins in small intestine of iron-deficient rats
Authors: Buts J. P. , Vamecq J. , van Hoof F.
Published: December 2017

We studied the activity and kinetic parameters of microvillous enzymes in intestinal villous cells and the concentration of the secretory component (SC) of p-immunoglobulin A in subcellular fractions of crypt cells in 35-day-old rats made iron deficient from birth and in controls. The aim of the study is to investigate the biochemical basis for the decreased activity of brush-border disaccharidases observed in growing animals with chronic iron deficiency. In rats made iron deficient, the specific (per unit protein) and the total (per total intestinal length) activities of sucrase, lactase, maltase, aminopeptidase, and diamine oxidase were decreased from -17 to -66% compared with the activities measured in the controls. The lower activity of sucrase in the brush-border membrane of the iron-deficient rats was associated with much slower enzyme synthesis rate than in control animals. Km of sucrase was identical in both iron-deficient rats and controls, but the maximum velocity of enzyme reaction was reduced proportionally to the enzymatic activity, indicating a lesser amount of enzyme rather than an inactivation. Electron microscopy of epithelial villous cells from iron-deficient rats revealed a marked rarefaction of secretory granules (transport vesicles) without apparent change in the morphology of the brush-border membrane or of cellular organelles. In villus and crypt cells isolated from the jejunum of iron-deficient rats, SC concentration was reduced to a level about half that of the controls. When SC concentration was measured in subcellular fractions of crypt cells, SC content in each fraction was two to three times lower in iron-deprived rats than in controls without evidence of accumulation of the protein at a given subcellular level.(ABSTRACT TRUNCATED AT 250 WORDS)
Microvascular actions of platelet-activating factor on rat gastric mucosa and submucosa
Authors: Whittle B. J. , Morishita T. , Ohya Y. , Leung F. W. , Guth P. H.
Published: December 2017

Intravenous infusion of platelet-activating factor (PAF or AGEPC) induces extensive acute hemorrhagic damage in the ra gastric mucosa. The effects of PAF have now been investigated on several microcirculatory parameters in the rat gastric mucosa. Infusion of PAF (25–100 ng X kg-1 X min-1 iv) dose-dependently reduced systemic arterial blood pressure and mucosal blood flow, as determined by hydrogen gas clearance. Microscopic observation likewise indicated a dose-dependent slowing of mucosal capillary blood flow, as determined by red blood cell velocity after PAF infusion with stasis of flow at the highest dose. These actions were not the consequence of vasoconstriction, since there was no significant change in arteriolar and venular vessel diameter in the submucosa during PAF infusion, although a dose-related slowing and stasis of blood flow was observed. There was no capillary leakage of plasma protein in the gastric mucosa during PAF infusion, as determined by a fluorescence marker (FITC-BSA) technique. The precursor and breakdown product, lyso-PAF (200 ng X kg-1 X min-1) had no significant action on any of these microcirculatory parameters. These observations support the suggestion that microvascular changes leading to stasis may contribute to the ulcerogenic actions of PAF.
Neurotensin stimulates [3H]oleic acid translocation across rat small intestine
Authors: Armstrong M. J. , Parker M. C. , Ferris C. F. , Leeman S. E.
Published: December 2017

The effect of neurotensin (NT) on the translocation of intraluminally administered lipid across the duodenum as well as across the entire length of the small intestine was studied in the rat. In the first series of experiments, the appearance in the lymph of [3H]oleic acid instilled as a bolus into a segment of the duodenum was followed for 3 h. Infusion of NT (0.6 pmol X kg-1 X min-1) via the superior mesenteric artery resulted in a significant increase in the appearance of label in the lymph when compared with saline infusion (17.3 +/- 3.1 vs. 8.6 +/- 1.4%, P less than 0.01, respectively). In the second series of experiments, lipid was infused into the entire length of the small intestine over 4 h, and the accumulation of label in the lymph was measured. The infusion of NT (1.0 pmol X kg-1 X min-1) into the femoral vein also significantly increased the appearance of label when compared with animals infused with saline (49.0 +/- 2.0 vs. 34.2 +/- 5.2%, P less than 0.05, respectively). In this study, the specific activity of the triglyceride recovered in the lymph was higher in the rats given NT than in the controls (P less than 0.05). No significant changes in lymph flow were observed as a consequence of NT infusion. These results indicate that NT infusion into the circulation increases the translocation of oleic acid from the intestinal lumen into the lymph of rats.
The relationship of ornithine decarboxylase and thymidine kinase to mirex-induced liver growth
Authors: Yarbrough J. D. , Grimley J. M. , Karl P. I.
Published: December 2017

To investigate the sequence of events that occur in the liver during mirex-induced adaptive liver growth, [3H]thymidine incorporation into DNA, thymidine kinase (TK), and ornithine decarboxylase (ODC) were studied in intact and adrenalectomized (ADX) mirex-dosed rats, and the responses were compared with experimental groups receiving corticosterone. In intact mirex-dosed rats (a response that is both hyperplastic and hypertrophic) there was a 36-h peak in ODC activity, and a 48-h peak in both [3H]thymidine incorporation into DNA and TK activity. This was accompanied by a 72% increase in relative liver weight (RLW). In contrast, in ADX mirex-dosed rats (a predominately hyperplastic response), there was a biphasic ODC response (18- and 36-h peaks), a 36-h TK peak, and a 48-h peak in [3H]thymidine incorporation into DNA. Both TK activity and [3H]thymidine incorporation into DNA were significantly elevated for the remainder of the 96-h study period. There was a 38% increase in RLW. Corticosterone supplements to mirex-dosed intact rats resulted in a biphasic peak of TK activity (30- and 48-h peaks), a reduced ODC peak at 36 h, and a 48-h peak in [3H]thymidine incorporation into DNA. RLW response was similar to the response in intact mirex-dosed rats. Corticosterone supplements to mirex-dosed ADX rats eliminated the 48-h peak of [3H]thymidine incorporation into DNA, reduced TK activity and shifted the peak to 30 h, and eliminated the ODC biphasic response. The RLW increase was similar to the response in intact mirex-dosed rats with a maximum 80% increase at 72 h postmirex dose.
Homologous desensitization to prostaglandins in rabbit ileum
Authors: Musch M. W. , Field M. , Miller R. J. , Stoff J. S.
Published: December 2017

Prostaglandins (PG's) increase short-circuit current (Isc), inhibit NaCl absorption, and stimulate Cl secretion in rabbit ileum. These changes occur with the following PGs; E2, E1, nitrilo-I2 and, to a lesser extent, with A2, D2, and F2 alpha. Arachidonic acid (AA) also stimulates secretion. The PG- or AA-stimulated Isc does not persist, however, and on prolonged exposure tachyphylaxis develops. Resensitization of the Isc response to PGE2 is rapid, being essentially complete in 15 min after the PG is removed. Desensitization to AA is not reflected by diminished PG generation. PGE2 release from the mucosa after AA addition is constant, although the AA-stimulated Isc decreases. Isc measurements indicate that PGE2 at slightly below its EC50 partially desensitizes and a near-maximal concentration completely desensitizes to PGE2 but does not, however, inhibit the subsequent change in Isc caused by theophylline or vasoactive intestinal peptide (VIP). Adenosine 3',5'-cyclic monophosphate (cAMP) measurements suggest that desensitization applies to cAMP production. PGE2 (10(-5) M) increases mucosal cAMP three- to sevenfold, but this elevation is transient; a second challenge dose, which fails to elicit a Isc change, also fails to increase mucosal cAMP. Adenylate cyclase measurements from untreated and PGE2-treated enterocytes demonstrate a decrease in stimulation by PGE2 but not in stimulation by VIP, fluoride, or 5-guanylylimidodiphosphate.
Flow across the canine ileocolonic junction: role of the ileocolonic sphincter
Authors: Kruis W. , Phillips S. , Zinsmeister A.
Published: December 2017

The role of the canine ileocolonic sphincter (ICS) in influencing transit of fluids and absorption of water in the ileum was assessed in loops with or without the ICS. Two sets of four dogs each were equipped with isolated ileal loops 40 cm long, attached to the intact bowel through a neuromuscular bridge. In one set, the loop included the ICS and it terminated in an end colostomy; in the other, the loop ended immediately proximal to the ICS, as an ileostomy. Electrical and mechanical signals were recorded from serosal electrodes and strain gauges, respectively, during perfusion of loops with an isotonic solution at rates from 0.7 to 10.0 ml/min. Loops without an ICS propelled fluid by steady, continuous flow at all rates of perfusion; loops with the ICS in place moved fluids in this way only at 10 ml/min. At greater rates of perfusion, fasting cycles of motility were inhibited in all loops and a random pattern of motility developed; this presumably facilitated more steady flow of fluids. At the slowest rate of perfusion, transit times were longer when the ICS was present, but at faster rates both loops showed similar transit times. Presence of the ICS was associated with increased volumes of fluid in the loop and increased absorption of water, especially when loops were perfused slowly. The canine ICS influences flow of saline and absorption in the terminal ileum, but only when flow rates are low.
Coordination of electrical activities in muscle layers of the pig colon
Authors: Huizinga J. D. , Chow E. , Diamant N. E. , el-Sharkaway T. Y.
Published: December 2017

Simultaneous recording of electrical activities from the circular and longitudinal muscle layers of the pig colon was performed in vitro to study possible coordination of activities. The electrical activity of both muscle layers consisted of electrical oscillations with superimposed spikes. The frequency range of the electrical oscillations in the circular muscle was 0.5-3.5 cycles per minute (cpm) and in the longitudinal muscle 24-42 cpm. Coordination of the activities of both muscle layers occurred consistently only after stretch or cholinergic stimulation. Then it occurred in a unique fashion. Each oscillation in the circular muscle layer occurred at the same time as the onset of a burst of oscillations in the longitudinal muscle. In addition, multiple simultaneous recordings of the electrical activities from each muscle layer were obtained showing that within the circular muscle layer electrical oscillations were phase locked in the circumferential direction and along the long axis of the colon. They appeared to propagate in either the oral or aboral direction. In tetrodotoxin (with stretch as stimulus) and also in presence of carbachol, bursts of oscillations in the longitudinal muscle layer were phase locked circumferentially (in the different taeniae) and longitudinally. This study shows that the muscle layers in the colon, which have different myogenic electrical activities, can obtain a high level of coordination.
Effects of luminal salt concentration on electrical pathways in Necturus antrum
Authors: Soybel D. I. , Ashley S. W. , Swarm R. A. , Moore C. D. , Cheung L. Y.
Published: December 2017

By use of microelectrode techniques the electrical resistances of the cell membranes and paracellular pathways of surface epithelium in Necturus antrum were determined under control conditions (Ringer solutions containing 106.6 mM Na+, 91.4 mM Cl-) and during exposure to mucosal solutions containing high Na+ and Cl- concentrations. Resistances were determined by briefly exposing tissues to mucosal solutions containing 10(-4) M amiloride, a reversible inhibitor of Na+ conductances. Under control conditions in eight tissues, measurements obtained by exposure to amiloride were not significantly different from those obtained by an independent method, intraepithelial cable analysis, thus indicating the validity of the measurements obtained by the amiloride method. In 10 tissues, high luminal NaCl concentrations (Ringer salts + 125 mM NaCl) increased the apical cell membrane resistance from 5,778 +/- 267 to 7,714 +/- 422 omega X cm2 (P less than 0.01) and the basolateral membrane resistance from 2,973 +/- 186 to 3,869 +/- 335 omega X cm2 (P less than 0.01). The resistance of the paracellular pathway decreased from 625 +/- 13 to 505 +/- 13 omega X cm2 (P less than 0.001). Similar alterations in these resistances were observed when Na+ or Cl- were increased individually, when added as salts of isethionate- and N-methyl-D-glucamine+, respectively. These effects were not attributable to increases in luminal osmolarity, since mucosal solutions made equally hyperosmotic with 250 mM sucrose elicited increases in paracellular pathway resistance and decreases in resistances of the cell membranes.(ABSTRACT TRUNCATED AT 250 WORDS)
Ontogeny of rat gastric H+-K+-ATPase activity
Authors: Hervatin F. , Moreau E. , Ducroc R. , Garzon B. , Avril P. , Millet P. , Geloso J. P.
Published: December 2017

Gastric H+-K+-ATPase activity was examined in subcellular fractions (P1, 1,000 g; P2, 20,000 g; P3, 100,000 g) obtained from fundic mucosae of fetal, newborn, and adult rats. Depending on the tissue secretory state the distribution of this enzyme activity predominates in P3, i.e., resting adult, or in P2, i.e., stimulated adult, while total enzyme activity (P2 + P3) remains constant. Enzyme activity was detected as soon as day 19 of gestation and P2 + P3 reached 2.2 +/- 0.2 mumol Pi X mg prot-1 X h-1 at parturition. H+-K+-ATPase activity steadily decreased from 4.0 +/- 0.7 mumol Pi X mg prot-1 X h-1 on day 6 after birth to approximately 0 on day 12. This activity recovered as soon as day 13 (3.5 +/- 0.6 mumol Pi X mg prot-1 X h-1) and continued to rise slowly until adulthood. Incubation of subcellular fractions with 0.1 mM omeprazole resulted in a total loss of H+-K+-ATPase activity at all the stages of development examined. These studies of functional relationship during the development between gastric acid secretion and distribution of gastric H+-K+-ATPase activity among P2 and P3 fractions indicate that this last could be considered as an index of the secretory state of the parietal cell. This enzyme's pattern of development in P2 + P3, correlated with the one previously observed for stimulated H+ secretion in intact tissue, suggest that the H+-K+-ATPase is the limiting step in response to secretagogues during postnatal period.
Gastrin is not a physiological regulator of pancreatic exocrine secretion in the dog
Authors: Kohler E. , Beglinger C. , Eysselein V. , Grotzinger U. , Gyr K.
Published: December 2017

The role of gastrin as a regulator of exocrine pancreatic secretion has not been proven adequately. In the present study we therefore compared the relative molar potencies of sulfated and unsulfated gastrin 17 with structurally related CCK peptides (synthetic CCK-8 and natural porcine CCK-33) in stimulating exocrine pancreatic secretion in conscious dogs. Dose response curves were constructed for pancreatic and gastric acid secretion. Plasma gastrin levels after exogenous gastrin 17-I and -II were compared with postprandial gastrin concentrations (meal: ground beef 20 g/kg body wt). The molar potency estimates calculated with synthetic CCK8 as standard (potency = 1.00) for pancreatic protein secretion were natural porcine 50% pure CCK-33 1.60, gastrin 17-I 0.12, and gastrin 17-II 0.16. All four peptides induced a dose-dependent increase in pancreatic bicarbonate output. However, the blood concentrations needed to stimulate pancreatic secretion were above the postprandial gastrin levels. Our data indicate that both gastrin 17 peptides are not physiological regulators of pancreatic enzyme secretion in dogs.
Regulation of transmembrane electrical potential gradient in rat hepatocytes in situ
Authors: Fitz J. G. , Scharschmidt B. F.
Published: December 2017

The transmembrane electrical potential gradient (Em) has been measured in hepatocytes from intact anesthetized rats using conventional intracellular microelectrodes under a variety of conditions. Em measurements in control animals were normally distributed around a mean of -35.5 +/- 4.6 mV (SD) with a coefficient of variation (CV) of 13.1% and a range of -26 to -54 mV. In individual livers, however, measurements of Em at a given point in time exhibited little cell-to-cell variation (cv of 4.5%). The Em was noted to fluctuate spontaneously over time and to change consistently in response to a variety of physiological stimuli including fasting (depolarization to -28.5 +/- 3.8 mV) and infusion of glucagon in physiological amounts (hyperpolarization to -45.0 +/- 1.8 mV). Hepatocyte Em abruptly depolarized (2-5 mV) after an intravenous bolus of taurocholate (3 mumol) or alanine (45 mumol), suggesting that both solutes exhibit electrogenic uptake. The Em returned to or below preinfusion values within 5 min. Continued infusion of alanine (10.8 mumol/min), but not taurocholate (810 nmol/min), caused a sustained and unexpected hyperpolarization of Em of 8.2 +/- 3.1 mV that lasted at least 60 min. In separate studies, alanine administration did not alter the biliary excretion of a taurocholate load. Taken together, these observations demonstrate that rat hepatocytes in situ are tightly coupled electrically and that physiological stimuli, including fasting, glucagon, and sodium-coupled solute uptake can change Em considerably over time. The late hyperpolarization of Em caused by alanine appears to offset the rise in intracellular Na+ associated with alanine uptake and preserve the Na+ electrochemical gradient such that Na+-coupled taurocholate transport is maintained.
Liver cell membrane solubilization may control maximum secretory rate of cholic acid in the rat
Authors: Yousef I. M. , Barnwell S. , Gratton F. , Tuchweber B. , Weber A. , Roy C. C.
Published: December 2017

The factors modulating the maximum secretory rate of cholic acid were investigated. Rats were infused intravenously with cholic acid in measured stepwise increasing doses (1, 2, 3, and 4 mumol X min-1 X 100 g body wt-1). Each dose was infused for 30 min and bile samples were collected every 10 min. Bile flow, bile acid, cholesterol, individual biliary phospholipids, and the fatty acid profiles of the biliary phospholipids were determined. Microsomal and bile canalicular membrane-enriched fractions were isolated from cholic acid-treated rats at the end of the experiment. Membranes were analyzed for cholesterol, phospholipid, and phospholipid fatty acid composition. During cholic acid infusion, the secretion rates of bile acid, cholesterol, phospholipid, and bile flow initially increased and then declined. No evidence of liver cell damage was observed by light or electron microscopy. Maximum phospholipid secretion rate (13.5 nmol X min-1 X g-1) occurred before peak bile flow and bile acid secretory rate maximum (4.72 microliter X min-1 X g-1 and 375 nmol X min-1 X g-1). When phospholipid output declined, the proportion of sphingomyelins and phosphatidylethanolamine relative to phosphatidylcholine increased. This was also reflected in the fatty acid composition. Cholic acid infusion caused a decline in microsomal and bile canalicular membrane phospholipid content without affecting their phospholipid composition. Depletion of membrane phospholipid resulted in an increase in the cholesterol:phospholipid ratio, which is suggested to be the underlying mechanism for modulating cholic acid secretion.
Pressure and length adaptations in isolated cat stomach
Authors: Schulze-Delrieu K. , Shirazi S. S.
Published: December 2017

Correlations were made between the adaptation of gastric pressure and longitudinal muscle tension. Isolated cat stomachs were filled with physiological solution and longitudinal strips marked in five segments over the lesser and the greater curvature (LC and GC). Strip length changed the most in the proximal segments of GC. Volume changes led to triphasic changes in gastric pressure. On filling, there was a pressure peak and pressure accommodation to a new base-line pressure. On emptying there was an initial pressure nadir that was followed by a pressure recovery. When isolated longitudinal strips were stretched and released to their lengths at specific gastric volumes, they generated triphasic tension adaption and recovery. Strips from the proximal greater curvature generated the highest base-line tension, highest peak tension, and largest amplitude of tension adaptations. Addition of KCl, carbachol, or physostigmine increased base-line tension and tension adaptations in parallel, whereas atropine reduced them. Tetrodotoxin had no effect. The base-line tension of the isolated cat stomach is maintained by a tonic cholinergic neurosecretion but its tension adaptations do not require neural control.
Calcium transport by rat duodenal villus and crypt basolateral membranes
Authors: Walters J. R. , Weiser M. M.
Published: December 2017

Rat duodenal cells were isolated sequentially to give fractions enriched for villus and crypt cells. From each of these fractions, basolateral-enriched membrane vesicles were prepared and ATP-dependent calcium uptake was studied. Calcium uptake was sensitive to temperature, was inhibited by vanadate and by A23187, and was lower in vitamin D-deficient animals. In normal animals, calcium transport was approximately twofold greater in villus-tip than in crypt cell-fraction basolateral membranes though the affinity of the uptake for calcium was similar (Km = 0.3 microM). In vitamin D-deficient animals, the crypt-to-villus gradient was reduced, and in all fractions, calcium transport was similar to or lower than that in the crypts of normal animals. Six hours after vitamin D-deficient animals were repleted with 1,25-dihydroxycholecalciferol, a significant increase in calcium transport by everted gut sacs was present; however, basolateral calcium transport was significantly increased in only the mid-villus fractions, and no change was seen in the villus-tip fractions. Thus vitamin D appears necessary for the development of increased basolateral membrane calcium pump activity in duodenal villus cells, but not all cells in vitamin D-deficient rats are able to respond to 1,25-dihydroxycholecalciferol.
Intestinal blood flow and oxygen uptake in the neonatal piglet during reduced perfusion pressure
Authors: Nowicki P. T. , Hansen N. B. , Menke J. A.
Published: December 2017

The effect of reduced perfusion pressure on neonatal intestinal blood flow, vascular resistance, arterio-venous oxygen content (a-v O2), and oxygen uptake was studied in nine fasted newborn piglets, aged 5-6 days. Successive reductions of intestinal perfusion pressure were achieved by a clamp on the thoracic aorta. Intestinal blood flow decreased after each reduction of perfusion pressure. Intestinal vascular resistance increased and Gf, a measure of flow control, was negative after all but the final, most severe reduction of perfusion pressure. However, intestinal a-v O2 increased after each pressure reduction and intestinal oxygen uptake was thus maintained at greater than or equal to 95% of its baseline value until perfusion pressure was reduced to less than or equal to 70% of its base-line value. The neonatal intestine maintains tissue oxygen uptake during moderate hypotension, and this is accomplished by regulation of a-v O2, rather than by regulation of blood flow.