bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of substance P on colonic mechanoreceptors, motility, and sympathetic neurons
Authors: Krier J. , Szurszewski J. H.
Published: December 2017

Intracellular recording techniques were used in vitro to analyze the effects of substance P (SP) on synaptic transmission and electrical properties of sympathetic neurons in the inferior mesenteric ganglion (IMG) of the guinea pig. Intraluminal pressure-recording techniques were used to study the effects of SP on colonic motility. Superfusion of the ganglia with SP (10(-7) to 10(-6) M) depolarized the cell soma (2--12 mV) and increased cell input resistance (8--11 M omega). These effects converted synchronous excitatory postsynaptic potentials, in response to electrical stimulation of preganglionic nerves, and asynchronous excitatory postsynaptic potentials, in response to activation of colonic mechanoreceptors, to action potentials. Administration of SP to only the colon increased basal intraluminal pressure and the frequency and amplitude of phasic changes in intraluminal pressure. These changes increased mechanoreceptor synaptic input to neurons in the IMG. We conclude that SP facilitates synaptic transmission along noradrenergic pathways and increases colonic motility.
Does calcium mediate slowing of gastric emptying by fat in humans?
Authors: Hunt J. N.
Published: December 2017

The relative potencies of 47 compounds in slowing gastric emptying in one subject are given. The majority of the most effective compounds are detergent, but all detergents do not slow gastric emptying. It is proposed that the property common to those detergents that slow gastric emptying is the binding of ionized calcium. Disodium edetate (EDTA) is not a detergent. It has a high affinity for calcium, and it slows gastric emptying strongly. Reasons are given for proposing that decreasing the volumes of the lateral intercellular spaces of the luminal half of the duodenal villi mediates the slowing of gastric emptying by carbohydrate, protein, fats, and acids. Osmotic stimuli in the duodenal lumen, or in the enterocytes, reduce the flux of water into the lateral intercellular spaces. Anions of fatty acids and hydrogen ions displace calcium from a site on the tight junctions at the luminal border of the enterocytes. As a result, the tight junctions become more permeant to water and the lateral intercellular spaces shrink as their content drains into the duodenal lumen. Shrinking of the lateral intercellular space is proposed as the final common event in the transduction of the duodenal stimuli that slow gastric emptying.
Action of thiocyanate on pH gradient formation by gastric microsomal vesicles
Authors: Reenstra W. W. , Forte J. G.
Published: December 2017

The effects of thiocyanate anion (SCN-) on proton accumulation and ATP hydrolysis by hog gastric microsomal vesicles have been investigated. The addition of SCN- to vesicles in the presence of KC1 and valinomycin reduced ATP-dependent proton accumulation in a dose-dependent manner. Inhibition was most pronounced in the presence of internal SCN-, which was obtained by preincubation of vesicles with SCN- or by the addition of K+-valinomycin, which facilitates entry of SCN-. SCN- does not appear to act by inhibition of the vesicular H+ pump because 1) there were minimal effects of SCN- on the rate of ATP hydrolysis, and 2) the initial rate of pH gradient formation was greater with 20 mM SCN- than with 20 mM Cl-. In the presence of K+ and valinomycin, external SCN- inhibited ATP-dependent pH gradient formation by increasing the rate of proton efflux. Preformed pH gradients (acid interior) were rapidly dissipated by internal, but not external, SCN-. These results suggest that SCN- acts to increase the rate of passive proton loss from the vesicle interior and do not support a direct inhibition of ATP-dependent H+ translocation. The results are consistent with the formation of the permeant hydrothiocyanic acid within the vesicles, increasing the rate of proton loss. The data also lend support to the HSCN backflux hypothesis of Sanders et al. [Am. J. Physiol. 234 (Endocrinol. Metab. Gastrointest. Physiol. 3): E120-E128, 1978] for inhibition of gastric acid secretion by SCN-.
Differential effect of taurocholic acid on hepatic arterial resistance vessels and bile flow
Authors: Lautt W. W. , Daniels T. R.
Published: December 2017

The "hepatic arterial buffer response" hypothesis states that the hepatic artery is not controlled by liver parenchymal cell metabolic activity. Bile salts stimulate liver metabolism (elevate bile formation) and dilate the hepatic artery. The present data show that the vascular and metabolic effects in cats anesthetized with pentobarbital sodium are independent. Low doses of taurocholate (1 microM . min-1 . kg-1) produce metabolic but not vascular responses. At higher doses both the hepatic artery and superior mesenteric artery dilate with equal sensitivity. Taurocholate into the portal vein produced elevated bile flow and hepatic arterial dilation; infusion via the hepatic artery resulted in equal metabolic responses but much greater vascular effects. In addition, the time course of onset and termination of the metabolic and vascular responses supports the conclusion that the effects of taurocholic acid on hepatic bile flow and hepatic arterial flow are independent actions. This adds further support for the hepatic arterial buffer response being controlled by factors other than local hepatic metabolic demands.
Uptake of iopanoic acid by isolated rat hepatocytes in primary culture
Authors: Barnhart J. L. , Witt B. L. , Hardison W. G. , Berk R. N.
Published: December 2017

Uptake of iopanoic acid (IOP) was studied in 3-day primary cultures of rat hepatocytes isolated by the collagenase perfusion method. 125I activity of cells after incubation with 125I-IOP (1.0–100 microM) was used as a measure of uptake. At each IOP concentration uptake was linear for the first 45 s. The initial uptake velocity was directly proportional to IOP concentration and was nonsaturable up to 100 microM. The calculated uptake rate constant was 0.67 nmol . mg prot-1 . min-1 . microM-1. Uptake was only slightly reduced when the incubation was performed at 4 degrees C and was independent of sodium concentration. Albumin in the medium reduced IOP uptake. Uptake, however, was always greater than that predicted from the unbound IOP concentration alone. The data indicate that the hepatocyte uptake of IOP occurs by both a passive process and a saturable process. The saturable uptake component depends on an albumin-IOP-hepatocyte interaction. The influence of albumin on uptake occurs possibly by an undefined specific cell surface phenomenon of albumin that promotes uptake of IOP or by enhancement of the diffusibility of IOP across the unstirred layer.
Bombesin-induced tachyphylaxis markedly enhances gastrin response to a meal
Authors: Larson T. , Sanchez J. , Taylor I. L.
Published: December 2017

This study was designed to determine whether a bombesinlike peptide mediated the gastrin response to food. Tachyphylaxis of gastrin release was induced in six dogs by prolonged infusion of bombesin (500 ng X kg-1 X h-1) before ingestion of a meal. An impaired postprandial gastrin response during bombesin tachyphylaxis would be indirect evidence that a bombesinlike peptide mediated the gastrin response to food. Serum gastrin concentrations peaked (74 +/- 18 pM) 1 h after commencement of the bombesin infusion and then fell significantly (P less than 0.01), reaching a nadir of 15 +/- 1 pM at 4 h. Dogs were then fed the standard meal (15 g/kg Prime dog food), and the serum gastrin response was compared with that observed in response to the meal ingested during saline infusion. There was sixfold enhancement (P less than 0.01) of meal-stimulated gastrin release during bombesin infusion compared with saline infusion. Stopping the bombesin infusion before ingestion of the meal still resulted in significant (P less than 0.05) enhancement of the meal response. Although pancreatic polypeptide responses to bombesin also exhibited tachyphylaxis, prolonged infusion of bombesin did not enhance the pancreatic polypeptide response to food. We conclude that a bombesinlike peptide does not mediate the gastrin response to food in dog. We speculate that bombesin stimulates both secretion and synthesis of gastrin but that only secretion is subject to tachyphylaxis. The enlarged secretory pool produces an enhanced response when the G cell is exposed to stimulants other than bombesin.
Effect of secretin and caerulein in canine pancreas: relation to prostaglandins
Authors: Homma T. , Malik K. U.
Published: December 2017

We investigated the effect of secretin and caerulein on pancreatic circulation and exocrine secretion and its relation to prostaglandin (PG) synthesis by studying the effect of these peptides on the pancreatic blood flow and the flow rate of pancreatic exocrine secretion in the isolated blood-perfused pancreas of pentobarbital-anesthetized dogs without or with pretreatment with the cyclooxygenase inhibitors, indomethacin and meclofenamate. Intra-arterial administration of secretin (0.1–0.3 U/kg) produced an initial vasoconstriction followed by vasodilation. On the other hand, caerulein (50–200 ng/kg) produced vasodilation and increased pancreatic blood flow in a dose-related manner. Both secretin and caerulein increased the flow rate of pancreatic exocrine secretion. In animals pretreated with either indomethacin or meclofenamate, the ability of secretin to produce an initial vasoconstriction was abolished and the subsequent vasodilator component of the response as well as caerulein-induced vasodilation were reduced in duration. The effect of caerulein but not of secretin to stimulate the flow rate of pancreatic exocrine secretion was reduced by indomethacin and meclofenamate. Administration of PGI2 and PGE2 into the pancreas caused vasodilation, whereas PGF2 alpha and PGD2 produced a biphasic effect, i.e., an initial vasoconstriction followed by vasodilation. Infusion of either PGI2 or PGE2 but not that of PGF2 alpha or PGD2 minimized the effect of cyclooxygenase inhibitors to reduce the duration of vasodilator response elicited by secretin and caerulein. Prostaglandins neither altered the basal nor the rise in flow rate of pancreatic exocrine secretion produced by secretin and caerulein. These data indicate that in the canine pancreas prostaglandins contribute to the effects of secretin and caerulein to increase pancreatic blood flow but not to their effect on pancreatic exocrine secretion.
Simultaneous estimation of arteriolar, capillary, and shunt blood flow of the gut mucosa
Authors: Dinda P. K. , Buell M. G. , DaCosta L. R. , Beck I. T.
Published: December 2017

Microspheres of 15 and 9 microns diameter were injected simultaneously into the left ventricle of the dog, and the entrapment of these microspheres in different layers of the gut wall was measured under resting conditions, vasoconstriction, and subsequent vasodilation. Results show that some of the 9-microns spheres passed into the portal blood through all layers of the gut wall, whereas 15-microns spheres were completely entrapped in the tissue. The pattern of entrapment of 15-microns spheres during vasoconstriction and during subsequent vasodilation suggests that these microspheres measure adequately the arteriolar inflow of the muscularis, submucosa, and mucosa (i.e., villus plus crypt) but, due to series arrangement between the arterioles of the villus and the crypt, cannot measure the arteriolar flow of the villus and crypt separately. The entrapment of 9-microns microspheres in the muscularis, submucosa, crypt, and villus that occurred during vasoconstriction did not change during subsequent vasodilation. This suggests that these microspheres became lodged in the precapillary sphincter or capillary and therefore measured the capillary flow of these layers. Accordingly, the difference between the arteriolar (measured by 15 microns) and the capillary (measured by 9 microns) flow of the muscularis, submucosa, and mucosa may provide an estimate of the noncapillary (shunt) flow of these layers.
Determinants of flow across isolated gastroduodenal junctions of cats and rabbits
Authors: Schulze-Delrieu K. , Wall J. P.
Published: December 2017

The resistance generated by the gastroduodenal junction was measured in isolated cat and rabbit preparations. Cannulas were tied into the antrum and duodenum. Yield pressures were determined by increasing the pressure in one of the cannulas until flow occurred. The junctional segment of the cat maintained a high yield pressure. Yield pressures were similar in the antroduodenal and the duodenogastric direction (12.5 +/- 5.7 vs. 14.8 5.8 cmH2O) and increased on both sides to the same degree following exposure of the preparation to 100 mM [K+] and to 10(-6) M carbachol. These experimental manipulations also led to the occurrence of pressure waves in the antral cannula. Yield pressures were diminished but not abolished by exposure of the preparation to 0 [Ca2+] solution or 10(-6) M isoproterenol. Junctional segments from the rabbit did not maintain a yield pressure. Resistance across the junctional segment of both species was also measured by channeling the outflow of one of the cannulas to a flowmeter. Over a wide range of pressures, flow rates across the junctional segment of the rabbit exceeded those across the junctional segment of the cat. Carbachol and 100 mM [K+] decreased the base-line flow and increased the amplitude of intermittent decreases of flow. Isoproterenol and 0 [Ca2+] had opposite effects. Inflation of a balloon decreased the flow rate across the rabbit but not the cat junctional segment. Flow rates across the junctional segment did not differ in the antroduodenal and duodenogastric direction. The gastroduodenal junction does not act as an unidirectional valve. Pyloric resistance relates to the structure of the pyloric segment and to phasic and tonic activity of its musculature.
Effect of luminal somatostatin on pentagastrin-stimulated gastric acid secretion in the rat
Authors: Morz R. , Prager-Petz J. , Pointner H.
Published: December 2017

The perfused rat stomach was used to investigate the effect of intragastrically administered somatostatin (S-14) on basal and pentagastrin-stimulated gastric acid secretion. Intravenous injection of pentagastrin (10 micrograms/kg body wt) induced a peak acid output (PAO) of 6.3 +/- 0.45 mu eq H+. With luminal perfusion of the stomach by S-14 (100 micrograms X kg-1 X min-1), no significant inhibition of gastric acid secretion was observed (PAO: 5.9 +/- 0.6 mu eq H+). The same dose of S-14 administered intravenously significantly inhibited acid secretion (PAO: 1.7 +/- 0.4 mu eq H+) as did intravenous injection of neutralized S-14-containing gastric perfusate obtained by perfusion from a different rat stomach (PAO: 1.9 +/- 0.5 mu eq H+). Intravenous injection of a saline gastric perfusate containing no S-14 did not alter gastric acid secretion (PAO: 6.3 +/- 0.7 mu eq H+). It is concluded that S-14 does inhibit gastric acid secretion when administered systemically but not by intraluminal application.
Dietary-induced rapid decrease of microvillar carbohydrase activity in rat jejunoileum
Authors: Goda T. , Yamada K. , Bustamante S. , Koldovsky O.
Published: December 2017

Activities of several carbohydrases and peptidases were determined in proximal, middle, and distal thirds of the jejunoileum of female 16-wk-old rats that were fed a high-starch (70 cal%), low-fat (7 cal%) diet for 2 wk and also in rats that (after this introductory period) were fed an isocaloric low-starch (5 cal%), high-fat (73 cal%) diet for 1, 2, and 3 days. The body weight changes, food intake, amount of protein per intestinal segment, and rate of enterocyte migration were practically the same in all groups during these experimental periods. The decreased intake of starch was followed by a rapid decrease (40-80%) of carbohydrases (lactase, sucrase, maltase, and glucoamylase) within the first 24 h in total intestinal homogenates--and as studied in cryostat serial sections--in all regions of the jejunal villus-crypt columns, and mainly in proximal and middle segments. In contrast, the activities of leucylnaphthylamidase and L-phenylalanylglycine hydrolase exhibited little change except for a slight temporary decrease of activity on the 1st day in the proximal segment only (25-30%). Thus these data show that a decrease of starch content in an isocaloric diet evokes a rapid decrease in the activity of microvillar carbohydrases and that activity of these enzymes both in mature and immature enterocytes is capable of reacting to a change (decrease) of dietary carbohydrate content.
Pentagastrin potentiates nonadrenergic inhibitory neuromuscular transmission in orad stomach of the dog
Authors: Schmalz P. F. , Morgan K. G. , Szurszewski J. H.
Published: December 2017

Mechanical and intracellular electrical activities were recorded separately from circular muscle of the orad corpus of the canine stomach. In normal Krebs solution, transmural electrical nerve stimulation produced excitatory and inhibitory responses. The excitatory response was blocked by atropine; the inhibitory response was unaffected by phentolamine or propranolol alone or in combination. Both responses were blocked by tetrodotoxin. In the presence of pentagastrin, the inhibitory response to electrical nerve stimulation was potentiated in a dose-dependent manner. The threshold concentration for this potentiating effect was 3 X 10(-11) M. Intracellular recordings showed that hyperpolarization of the resting membrane potential in response to inhibitory nerve stimulation was greater in the presence of pentagastrin than in its absence. These data suggest that, in addition to a direct stimulatory effect on the muscle, pentagastrin also potentiates the effect of ongoing activity of intramural inhibitory nerves. This latter effect is only apparent when the inhibitory neural network is active. Thus, the in vivo effect of pentagastrin on motor activity of the corpus will depend on the degree of ongoing activity of intramural inhibitory nerves.
Differing effects of norcholate and cholate on bile flow and biliary lipid secretion in the rat
Authors: O'Maille E. R. , Kozmary S. V. , Hofmann A. F. , Gurantz D.
Published: December 2017

The effects of norcholate (a C23 bile acid that differs from cholate in having a side chain containing four rather than five carbon atoms) on bile flow and biliary lipid secretion were compared with those of cholate, using the anesthetized rat with a bile fistula. Norcholate and cholate were infused intravenously over the range of 0.6-6.0 mumol X min-1 X kg-1. Both bile acids were quantitatively secreted into bile; norcholate was secreted predominantly in unconjugated form in contrast to cholate, which was secreted predominantly as its taurine or glycine conjugates. The increase in bile flow per unit increase in bile acid secretion induced by norcholate infusion [17 +/- 3.2 (SD) microliters/mumol, n = 8] was much greater than that induced by cholate infusion (8.6 +/- 0.9 microliters/mumol, n = 9) (P less than 0.001). Both bile acids induced phospholipid and cholesterol secretion. For an increase in bile acid secretion (above control values) of 1 mumol X min-1 X kg-1, the increases in phospholipid secretion [0.052 +/- 0.024 (SD) mumol X min-1 X kg-1, n = 9] and cholesterol secretion (0.0071 +/- 0.0033 mumol X min-1 X kg-1, n = 9) induced by norcholate infusion were much less than those induced by cholate infusion (0.197 +/- 0.05 mumol X min-1 X kg-1, n = 9, and 0.024 +/- 0.011 mumol X min-1 X kg-1, n = 9, respectively; P less than 0.001 for both phospholipid and cholesterol). The strikingly different effects of norcholate on bile flow and biliary lipid secretion were attributed mainly to its possessing a considerably higher critical micellar concentration than cholate.
Relation between intestinal motility and mesenteric blood flow in the conscious dog
Authors: Fioramonti J. , Bueno L.
Published: December 2017

Blood flow in a mesenteric artery and electrical activity of the corresponding segment of jejunum or ileum were simultaneously measured in eight conscious dogs. Each was fitted chronically with an electromagnetic flow probe and transparietal electrodes. In some dogs an intestinal cannula was placed cephalad to the segment investigated. Continuous 24-h records were obtained in each dog receiving a daily meal. Jejunal blood flow increased after the meal, decreased progressively during the postprandial period (7-12 h), and then exhibited cyclic variations associated with the occurrence of migrating myoelectric complexes (MMCs) during the next 6-10 h. The ileal blood flow increased, then remained high and nearly constant during the postprandial disorganization of the MMC pattern, and exhibited cyclic variations associated with all MMCs even when the dog was fasted for 48 h. Cyclic variations in blood flow were abolished when the intestinal content was drained through the cannula. It is concluded that in the conscious dog the blood flow profile in a mesenteric artery is associated with the motor profile of the segment. This association is due to the presence of digestive matter, probably nutrients in the jejunum and bile in the ileum.
Evidence for an opiate-mediated pyloric sphincter reflex
Authors: Reynolds J. C. , Ouyang A. , Cohen S.
Published: December 2017

The purpose of this study was to determine the mechanism by which the feline pylorus contracts in response to duodenal acidification. Simultaneous intraluminal pressures and serosal electrical activity were recorded from the antrum, pylorus, and duodenum of the anesthetized cat. The pylorus demonstrated a narrow zone of tonically increased pressure. Duodenal but not antral acidification increased the frequency and amplitude of phasic spike-associated pyloric contractions (P less than 0.001). This response was antagonized by tetrodotoxin, intraluminal (ethyl aminobenzoate), or naloxone. Bilateral cervical vagotomy, atropine, phentolamine, propranolol, cinanserine, diphenhydramine, or cimetidine had no effect on the pyloric response to duodenal acidification. Duodenal spike activity was also increased by duodenal acidification but was antagonized by atropine and not by naloxone. Leucine- or methionine-enkephalin intra-arterially produced dose-dependent increases in phasic pyloric contractions. The EDmax for leucin-enkephalin was 1.0 microgram/kg. The enkephalins inhibited duodenal spike activity in a dose-dependent fashion. These studies suggest that the pyloric spike-associated, high-amplitude phasic contractions in response to duodenal acidification involve local neural pathways that may be mediated through an opioid peptide. The pyloric response to duodenal acidification is distinguished from that of the duodenum, which is cholinergic.
Differing effects of hydroxy-7-oxotaurine-conjugated bile acids on bile flow and biliary lipid secretion in dogs
Authors: Danzinger R. G. , Nakagaki M. , Hofmann A. F. , Ljungwe E. B.
Published: December 2017

The effects on bile flow and biliary lipid secretion of two taurine-conjugated 7-oxo bile acids, 3 alpha-hydroxy-7-oxocholanoyltaurine (I) and 3 alpha,12 alpha-dihydroxy-7-oxocholanoyltaurine (II), were measured in the unanesthetized, chronic bile fistula dog. Each synthetically prepared compound, or cholyltaurine as control, was infused intravenously at a physiological rate of 1 mumol X kg-1 X min-1 for randomized 90-min periods. Bile samples were collected and analyzed for biliary lipids (bile acids, phospholipid, and cholesterol) and bile acid composition. Both compounds were secreted efficiently in bile, recovery averaging 90%. The trisubstituted compound (II) induced a greater choleresis and less phospholipid and cholesterol secretion than the disubstituted compound (I) or cholyltaurine. Each oxo compound was partially reduced during hepatic passage: about 47% of I (to mostly chenodeoxycholyltaurine) and about 30% of II (to mostly cholyltaurine). The effect of the individual bile acids on biliary lipid secretion was then calculated by assuming that a) the infused bile acid induced biliary lipid secretion after its hepatic biotransformation and b) each bile acid or its biotransformation product exerted an independent effect on biliary lipid secretion (expressed as a linkage coefficient, e.g., phospholipid secretion/bile acid secretion). For phospholipid, the calculated linkage coefficient for I was 0.31; for II, 0.07. For cholesterol, the calculated linkage coefficient for I was 0.014; for II, 0.003. In vitro studies indicated that the critical micellar concentration (CMC) in 0.15 M Na+ was 22 mM for I and 40 mM for II (compared with 6 mM for cholyltaurine.(ABSTRACT TRUNCATED AT 250 WORDS)
cAMP-mediated effects of ouabain and theophylline on paracellular ion selectivity
Authors: Bakker R. , Groot J. A.
Published: December 2017

We studied the effects of theophylline and ouabain on isolated intestinal mucosa of the goldfish. From continuous recordings of the intracellular potential difference, we concluded that theophylline has no considerable effect on the Cl- conductance of the apical membrane. Theophylline increased transepithelial conductance and bidirectional Cl- fluxes, while Na+ fluxes did not change appreciably. Both streaming potentials and NaCl dilution potentials were immediately reduced by theophylline. Moreover, we found a striking similarity between the effects of theophylline and ouabain. Ouabain initially increased transepithelial conductance, increased bidirectional Cl- fluxes, and instantly abolished NaCl dilution potentials. Determinations of cellular cAMP levels revealed that both theophylline and ouabain increase cAMP. The phosphodiesterase inhibitor theophylline amplified the ouabain-induced rise in cAMP, suggesting that ouabain stimulates adenylate cyclase. Since elevated extracellular K+ did not affect cAMP levels, it can be ruled out that depolarization of the cell membrane due to ouabain increases cAMP. We conclude that in this epithelium both theophylline and ouabain increase the Cl- permeability of the paracellular pathway by a cAMP-dependent mechanism.
Origin of sensation in the esophagus
Authors: Christensen J.
Published: December 2017

The sensory innervation of the esophagus is important both to physicians, for whom esophageal sensation can cause clinical confusion, and to physiologists, who wish to understand the regulation of esophageal motion. Sensory mechanisms in the gut in general are not well understood. Mechanoreceptive reflexes and their pathways, both parasympathetic and sympathetic, have been studied in the esophagus, and thermoreceptive reflex pathways that are parasympathetic have recently been described. The terminal sensory innervation of the esophagus contains several structures that may be receptors to such stimuli. Esophageal striated muscle contains muscle spindles like those of somatic muscle. Within the myenteric plexus, the bodies of certain ganglion cells themselves may be mechanoreceptive. Also, complex subcapsular laminar arborizations that arise from cells of the nodose ganglion have been described in ganglia of the esophageal myenteric plexus. Similar laminar arborizations have been found on vessels of the submucosa in the midesophagus. In the esophageal mucosa, the terminal innervation ends in structures of diverse form located both superficially and deep in the squamous epithelium. Thus, a variety of specific neural structures that seem to represent the terminals of sensory nerves exist in the esophagus and may serve the mechanoreceptive and thermoreceptive reflexes that modify esophageal motility.
Influence of enteric cholinergic neurons on mucosal transport in guinea pig ileum
Authors: Cooke H. J.
Published: December 2017

Electrical field stimulation was used to activate enteric neurons in the guinea pig ileum in order to determine the involvement of intramural cholinergic motor neurons in the control of mucosal sodium and chloride transport. Rectangular, bipolar stimulus pulses evoked a tetrodotoxin-sensitive biphasic increase in short-circuit current (Isc) that was due to an increase in active chloride secretion without any effect on active sodium absorption. During activation of enteric neurons, atropine, in concentrations of 5 X 10(-8) M or higher, reversibly abolished the rapid phase of the Isc and reduced the maximum sustained response to 40-50% of control values. Atropine reduced chloride secretion evoked by electrical stimulation and had no effect on sodium fluxes. Basal rates of sodium and chloride transport and tissue conductances were not altered by atropine. When muscarinic receptors were maximally stimulated with 10(-5) M carbachol, activation of enteric nerves increased Isc to 46% of control values. Bethanechol and eserine increased base-line Isc, and this effect was blocked by atropine but not by tetrodotoxin. The increase in Isc evoked by bethanechol was due to an increase in active chloride secretion. These results show that acetylcholine released by activation of enteric cholinergic motor neurons acts as muscarinic receptors on enterocytes to stimulate chloride secretion.
Effects of lactose on calcium absorption and secretion by rat ileum
Authors: Favus M. J. , Angeid-Backman E.
Published: December 2017

The direct effects of lactose on net intestinal calcium absorption were determined by measuring unidirectional steady-state calcium fluxes in vitro under short-circuited conditions in segments of rat ileum. The isosmotic mucosal additions in segments of rat ileum. The isosmotic mucosal addition of lactose (160 mM) increased net calcium absorption (J net) by increasing the absorptive flux from mucosa to serosa (Jm----s) and reducing the secretory flux from serosa to mucosa (Js----m). Lactose also reduced tissue conductance and short-circuit current and reversed tissue polarity. 1,25-Dihydroxyvitamin D3 administration (50 ng/day for 4 days) increased J net from secretion to no net flux (Jm----s = Js----m), and lactose increased J net further to net absorption. Removal of sodium from the medium, like lactose addition, increased J net by increasing Jm----s and reducing Js----m. The replacement of medium sodium with choline abolished a further increase of J net by lactose. These results show that lactose increases net calcium absorption in the absence of transepithelial electrochemical or osmotic gradients. Transcellular calcium transport may be stimulated by lactose by hyperpolarization of the brush border as a result of reduced mucosal sodium.
Effects of peptides on gastric emptying
Authors: Mangel A. W. , Koegel A.
Published: December 2017

The effects of peptides on gastric emptying of a liquid meal were studied in rats. Gastric emptying was found to be delayed following intraperitoneal injection of the octapeptide of cholecystokinin (CCK-8). Vasoactive intestinal peptide did not effect emptying, while substance P and neurotensin caused a moderate acceleration in gastric emptying. After oral administration of a solution containing the amino acids tryptophan and phenylalanine, but not glycine, a statistically significant inhibition of gastric emptying was observed. Our results suggest an involvement of CCK in the regulation of gastric emptying.
Induction of rat hepatic and intestinal alkaline phosphatase activity produced by bile from bile duct-ligated animals
Authors: Komoda T. , Kumegawa M. , Yajima T. , Tamura G. , Alpers D. H.
Published: December 2017

Bile duct ligation caused a threefold elevation of not only hepatic but also intestinal alkaline phosphatase. The increase was transient in intestinal mucosa and peaked at 12 h. Hepatic phosphatase levels reached a plateau by 36 h. Intraperitoneal injection of bile from ligated animals into normal rats produced qualitatively similar results. Studies were performed to further characterize the induction of phosphatase activity in both tissues. The addition of bile from ligated animals to organ explants of liver and intestine produced a two- and threefold rise in activity, respectively. Therefore, neural and hormonal factors are not essential in producing this induction. The increased activity produced in vitro in both tissues was due to heat-stable and dialyzable factor(s) and was blocked by inhibitors of protein synthesis. In the intestine activity occurred over the entire brush border as demonstrated by electron microscopic histochemistry. In the liver, increased activity was noted over the entire plasma membrane and was not localized to the canalicular membrane. Tunicamycin treatment of liver and intestinal explants markedly suppressed the induced phosphatase activity. Simultaneous treatment with protease inhibitors restored some of the phosphatase activity. These findings suggest that glycosylation of the alkaline phosphatase might provide at least partial protection from proteolysis.
Regulation of digestion. I. Effects of glucose and lysine on pancreatic secretion
Authors: Grendell J. H. , Tseng H. C. , Rothman S. S.
Published: December 2017

Previous cell-free studies have shown that glucose selectively elicits the release of amylase from pancreatic zymogen granules, whereas lysine promotes the selective release of trypsinogen. To investigate the expression of these effects in situ, glucose or lysine was injected into the celiac artery of anesthetized rats, either alone or together with the pancreatic secretagogue cholecystokinin, to evaluate their effects on the secretion of amylase and trypsinogen by the pancreas. When given alone neither substance significantly changed the output of either enzyme. However, when given with cholecystokinin, each altered the effect observed with injection of cholecystokinin alone. The injection of glucose resulted in a twofold increase in both peak and total amylase output without significantly increasing trypsinogen secretion, whereas lysine increased both peak and total trypsinogen output by about 50%, leaving amylase output unchanged. These findings provide in situ confirmation for the selective enzyme release produced by glucose and lysine in cell-free studies and suggest that such end products of digestion can regulate the digestive process by modifying the secretory response of the pancreas to cholecystokinin.
Supramaximal caerulein stimulation and ultrastructure of rat pancreatic acinar cell: early morphological changes during development of experimental pancreatitis
Authors: Watanabe O. , Baccino F. M. , Steer M. L. , Meldolesi J.
Published: December 2017

Rats infused with a supramaximally stimulating dose of the cholecystokinin-pancreozymin analogue caerulein develop acute interstitial pancreatitis (M. Lampel and H.F. Kern. Virchows Arch. A 373: 97-117, 1977). We have studied the early (30-180 min) morphological changes in pancreatic acinar cells induced by infusing caerulein (2.5 micrograms X kg-1 X h-1). The techniques of thin-section electron microscopy, freeze fracture, and enzyme and immunocytochemistry were employed. Shortly (30 min) after the onset of caerulein infusion, large vacuoles appeared in the Golgi area. After longer periods of infusion, these vacuoles further enlarged (probably by fusion with other such vacuoles as well as autophagic vacuoles) and became more widely distributed in the cytoplasm. These large vacuoles were found to be acid phosphatase positive and to be labeled by antibodies directed against digestive zymogens as well as the lysosomal enzyme cathepsin D. These observations indicate that the large vacuoles contain both digestive zymogens and lysosomal hydrolases. During caerulein infusion, morphological evidence of exocytosis at the luminal plasmalemma was reduced or absent, and evidence of basolateral exocytosis was not noted. These studies suggest that secretagogue hyperstimulation with caerulein interferes with the processes involved in condensing vacuole maturation, which normally lead to the separation of digestive zymogens and lysosomal hydrolases. As a result, both types of enzymes remain within the same compartment. This may lead to the intracellular activation of digestive enzymes by lysosomal hydrolases and be an important step in the development of acute pancreatitis.
Modulation of jejunal ion and water absorption by endogenous angiotensin after hemorrhage
Authors: Levens N. R.
Published: December 2017

In the pentobarbital sodium-anesthetized rat, hemorrhage of blood equivalent to 1% body weight (18.4% blood volume) increases plasma renin activity and plasma aldosterone concentration and also markedly elevates jejunal ion and water absorption. Infusion of angiotensin II (AII) also stimulates jejunal absorption, and in a manner similar to hemorrhage. The elevation of jejunal absorption in response to hemorrhage is not affected by removal of the adrenals but is totally inhibited by the converting enzyme inhibitor captopril and by bilateral nephrectomy. Thus, increased jejunal absorption following hemorrhage is mediated by the renin-angiotensin system and is not secondary to aldosterone release. Further experiments demonstrated that norepinephrine released from enteric sympathetic nerves controls jejunal absorption through activation of alpha-adrenergic receptors. The stimulation of jejunal absorption by tyramine was unaffected by propranolol but was totally abolished by phentolamine and by peripheral sympathectomy was 6-hydroxydopamine (intact adrenal medulla). The increase in jejunal absorption in response to hemorrhage also was unaffected by propranolol but was inhibited totally by phentolamine, prazosin, and peripheral sympathectomy. It is proposed that AII generated by hemorrhage facilitates norepinephrine release from enteric sympathetic nerves. The norepinephrine released by AII stimulates jejunal absorption by enhancing transepithelial transport processes or by altering the balance of Starling forces governing fluid absorption across enteric capillaries.
Systemic acid-base disorders and intestinal electrolyte transport
Authors: Charney A. N. , Feldman G. M.
Published: December 2017

Disorders of systemic acid-base balance have recently been shown to markedly alter intestinal electrolyte transport. These studies were based on earlier acid balance studies in humans and animals, data suggesting the presence of intestinal mucosal Na+-H+ and Cl-HCO-3 exchange processes and the reported effects of acid-base variables on other epithelia. In vivo studies have shown that intestinal net sodium and chloride absorption is markedly affected by systemic pH and carbon dioxide tension (Pco2). Specifically, systemic acidemia (in the rat ileum) and hypercapnia (in the rat colon) increase sodium and chloride absorption, while alkalemia and hypocapnia decrease absorption. In addition, net bicarbonate secretion (in both segments) varies directly with the plasma HCO3 concentration. The rabbit ileum has been studied both in vivo and in vitro and is affected in a similar way. The rat jejunum and rabbit distal colon and gallbladder do not respond to changes in blood pH and Pco2, consistent with the apparent absence of a mucosal Na+-H+ exchange process in these segments. Evidence suggests important roles for cellular carbonic anhydrase activity and the intracellular concentrations of hydrogen, bicarbonate, and calcium ions and calcium-calmodulin in mediating or modulating the effects of the systemic acid-base disorders. In addition, systemic pH may alter the effects of the neural and humoral mediators of intestinal transport.
Role of spontaneous portal-systemic shunting in hyperinsulinism of cirrhosis
Authors: Bosch J. , Gomis R. , Kravetz D. , Casamitjana R. , Teres J. , Rivera F. , Rodes J.
Published: December 2017

The possible contribution of hepatocellular damage and portal-systemic shunting to hyperinsulinism in cirrhosis was studied in 23 cirrhotics, 8 of whom had a surgical portacaval shunt, and 16 controls by measuring insulin and the connecting peptide (C-peptide) concentrations in simultaneous samples of peripheral arterial and hepatic venous blood. The fractional hepatic insulin extraction (0.48 +/- 0.06, mean +/- SE) was normal in cirrhosis. The hepatic insulin elimination rate was directly related to arterial insulin levels (r = 0.91, P less than 0.001) even at very high circulating levels. Extrahepatic insulin metabolism was measured across the kidney and lower limb. There were no significant differences between cirrhotics and control subjects in relation to renal (0.25 +/- 0.05 vs. 0.23 +/- 0.04) and lower limb insulin extraction (0.14 +/- 0.07 vs. 0.19 +/- 0.04). While in the control group hepatic venous insulin (0.143 +/- 0.018 pmol/ml) markedly exceeded the peripheral insulin concentration (0.083 +/- 0.009 pmol/ml, P less than 0.01), the contrary was found in cirrhotics with end-to-side portacaval shunt in whom all the pancreatic venous effluent is shunted to the systemic circulation (hepatic venous insulin, 0.130 +/- 0.028 pmol/ml; peripheral, 0.234 +/- 0.037 pmol/ml; P less than 0.01). Portal-hypertensive cirrhotics without a surgical portacaval shunt also had hepatic venous insulin levels (0.132 +/- 0.029 pmol/ml) below peripheral arterial insulin concentrations (0.205 +/- 0.041 pmol/ml, P less than 0.01). The study suggests that hyperinsulinism in cirrhosis is not the result of an intrinsic defect of hepatic insulin metabolism but of the spontaneous shunting of portal blood to the systemic circulation.
Effect of polycythemia on gastrointestinal blood flow and oxygenation in piglets
Authors: Nowicki P. T. , Oh W. , Yao A. , Hansen N. B. , Stonestreet B. S.
Published: December 2017

Gastrointestinal blood flow and oxygenation were measured before and after the induction of polycythemia in newborn piglets. Sixty minutes after exchange transfusion with age-matched packed red blood cells, hematocrit and in vitro whole blood viscosity increased, while 51Cr-measured blood volume did not change. Cardiac output and total gastrointestinal blood flow (the sum of stomach, jejunum, ileum, and colon blood flows) decreased a similar degree after exchange transfusion, although the reduction in total gastrointestinal blood flow was not uniform in all regions of the gastrointestinal tract. Specifically, blood flow to the stomach and mucosa-submucosa layer of the small bowel decreased, whereas that to the colon and muscularis-serosa layer of the small bowel remained unchanged. Gastrointestinal O2 delivery increased after exchange transfusion because of the increase in arterial O2 content consequent to polycythemia. The arteriovenous O2 content difference remained unchanged following exchange transfusion, and gastrointestinal O2 consumption thus decreased 49 +/- 2%. After a test meal, postprandial values for gastrointestinal blood flow and oxygenation in polycythemic piglets increased to levels similar to postprandial values reported previously in normal newborn piglets.
Gastrin release from isolated perfused rat stomach after vagotomy
Authors: Pederson R. A. , Kwok Y. N. , Buchan A. M. , McIntosh C. H. , Brown J. C.
Published: December 2017

Postvagotomy hypergastrinemia persists in the isolated perfused rat stomach, but its cause is unknown. The possible role of cholinergic nervous pathways was investigated in the isolated vascularly perfused rat stomach after vagotomy. Atropine and hexamethonium, but not propranolol, inhibited postvagotomy hypergastrinemia. A nervous mechanism involving acetylcholine was further suggested by the inhibitory action of methionine-enkephalin on gastrin release after vagal section. Methacholine, a muscarinic receptor agonist, only weakly stimulated gastrin release from vagotomized stomachs when compared with shamoperated controls, indicating that a cholinergic drive was already in place. Immunocytochemical studies of antral tissue following vagotomy indicated that numbers of gastrin-containing cells (G-cells) were not increased after vagotomy but exhibited reduced intensity of gastrin staining when compared with control stomachs. It was concluded that basal hypergastrinemia may result from increased stimulation of a normal G-cell population by a cholinergic mechanism at the ganglionic level.
Chymotrypsin, ileal chloride transport, and neurotransmitters
Authors: Hubel K. A.
Published: December 2017

Electrical field stimulation (EFS) depolarizes nerves and causes chloride secretion by mucosa of rabbit ileum mounted in a flux chamber. To test the hypothesis that the transmitter is a peptide, we determined whether the EFS response was prevented by the endopeptidase chymotrypsin (CT). Serosal, but not mucosal, addition of CT (200 micrograms/ml) reduced the short-circuit current (Isc) response to EFS by 90% or more. CT also reduced Cl absorption by decreasing the mucosal-to-serosal flux, but it did not affect net Na absorption. CT prevented the response to vasoactive intestinal polypeptides, but the response returned when CT activity was eliminated. The response to EFS did not return, however, implying that CT damaged cells that released transmitter or epithelial target cells. CT reduced the Isc response to serotonin by 69% and to A23187 by 10% and did not affect the theophylline response. We conclude that 1) the effects of CT on cell function limit its usefulness in identifying peptide neurotransmitters in epithelium, 2) CT irreversibly inhibits ion transport responses to EFS and to serotonin, and 3) CT reduces absorption of Cl probably by affecting a calcium pathway that modifies Cl transport.
Pressure activity patterns in the canine proximal stomach: response to distension
Authors: Azpiroz F. , Malagelada J. R.
Published: December 2017

The stomach accommodates to distension with a minimal rise in intragastric pressure, but the effects of gastric accommodation on overall gut motor activity are unknown. In four conscious fasted dogs, constant gastric distension (0, 10, 20, 40, 80, 160, 320, and 640 ml) was produced by an air-filled intragastric bag; intrabag and gastrointestinal pressure activities (fundus, antrum, and proximal intestine) were recorded for 4 h. With the bag empty (or without bag), the proximal stomach exhibited a fasting cyclic motor pattern synchronized with that in the antrum and upper intestine. During periods of activity the fundus generated powerful phasic pressure waves. Increasing intrabag volumes up to 80 ml gradually lengthened phase II of the intestinal interdigestive motor cycle. At 160 ml or more, gut cyclic motor activity disappeared and was replaced by continuous irregular activity, although the intrabag pressure increased to less than 7 mmHg. We concluded that gastric distension markedly alters gut motor activity even though gastric accommodation prevents a major increase in intragastric pressure.
Sympathetic stimulation and intestinal capillary fluid exchange
Authors: Granger D. N. , Barrowman J. A. , Harper S. L. , Kvietys P. R. , Korthuis R. J.
Published: December 2017

Sympathetic nerve stimulation is generally considered not to alter intestinal capillary pressure or filtration rate because of appropriate adjustments in the pre-to-postcapillary resistance ratio. To directly assess this possibility, we measured lymph flow, capillary pressure, capillary filtration coefficient, and the transcapillary oncotic pressure gradient in the cat small intestine. Measurements were taken under control conditions and during the steady-state phase of periarterial nerve stimulation, i.e., following completion of the escape phase. Venous outflow pressure was held constant (0 mmHg) during the entire experiment. Nerve stimulation resulted in a significant reduction of lymph flow (by 65%), capillary filtration coefficient (by 75%), and capillary pressure (by 15%). Interstitial fluid pressure, calculated from the measured parameters in the Starling equation, was also reduced (from -0.74 to -2.53 mmHg) by nerve stimulation. The results of this study indicate that intestinal capillary pressure and capillary filtration rate are not "autoregulated" during sympathetic nerve stimulation. Capillary derecruitment appears to be largely responsible for the dramatic reduction in filtration rate associated with adrenergic stimulation.