bluuebunny/crossref_metadata_2025 huggingface dataset:
Histamine, cAMP, and activation of piglet gastric mucosa
Authors: Machen T. E. , Rutten M. J. , Ekblad E. B.
Published: December 2017

The involvement of cAMP as a second messenger for histamine-induced H+ secretion was studied in a physiologically active, in vitro preparation of piglet gastric mucosa. During the first 5--10 min of stimulation with either histamine or the cAMP phosphodiesterase inhibitor 3-isobutyl-1,4-methylxanthine (IBMX), increases (greater than or equal to 5-fold) in tissue cAMP content [(c-AMP]) were well correlated with the characteristic decrease in transepithelial resistance (R); these changes precede H+ secretion by several minutes. Control experiments indicate that, during these treatments, tissue [cAMP] is dominated by the [cAMP] of oxyntic cells alone; change in R and H+ are also related to activity of these cells alone. At the steady state (45 min), histamine and IBMX caused equivalent increases in H+ and decreases in R, but [cAMP] was markedly different in the two cases. With IBMX [cAMP] was elevated at least fivefold, whereas with histamine [cAMP] was less than or equal to 50% above resting levels. The tissue is also stimulated by exogenous additions of dibutyryl cAMP. A histamine-sensitive adenylate cyclase was present in isolated, purified oxyntic cells. The histamine sensitivity of the cyclase was very similar to that which the intact tissue exhibits for histamine-induced changes in H+ and R. The cyclase activity was blocked by cimetidine but not by promethazine. We conclude that during stimulation histamine activates a histamine (H2)-sensitive adenylate cyclase of oxyntic cells, and there is a rapid increase in cellular [cAMP] that is involved in activation of H+ transport and other associated changes of oxyntic cells. An active phosphodiesterase is responsible for reducing [cAMP] to a level much below the "peak" value. Other cellular factors (e.g. protein kinases and Ca2+-calmodulin) must also be involved in the maintenance of the stimulated state of oxyntic cells.
Gastroduodenal HCO3(-) transport: characteristics and proposed role in acidity regulation and mucosal protection
Authors: Flemstrom G. , Garner A.
Published: December 2017

Gastric HCO3(-) transport (basal) studied in isolated amphibian mucosa and mammalian stomach in vivo amounts to 2-10% of maximal H+ secretion. Duodenal mucosa, devoid of Brunner's glands, transports HCO3(-) at a greater rate (per unit surface area) than either stomach or jejunum in vitro and in vivo. Gastric (but not duodenal) HCO3(-) transport is stimulated by dibutyryl cGMP, carbachol, and cholecystokinin and duodenal (but not gastric) transport by dibutyryl cAMP and gastric inhibitory peptide. Glucagon and E- and F-type prostaglandins stimulate, whereas histamine, gastrin, and secretin are without effect in both stomach and duodenum. Gastric transport very probably occurs by Cl--HCO3(-) exchange at the luminal membranes of the surface epithelial cells. In addition to this mechanism, the duodenum also transports HCO3(-) electrogenically. Lowering the luminal pH increases transport in both the stomach and duodenum. This response, probably mediated via both local production of prostaglandins and tissue-specific humoral agents, may be important in mucosal protection against acid. Metabolism-dependent transport of HCO3(-), stimulated by acid, seems quantitatively sufficient to account for all of the duodenal and most of the gastric mucosa's ability to remove luminal acid.
Relation between intestinal blood flow and oxygen uptake
Authors: Kvietys P. R. , Granger D. N.
Published: December 2017

In autoperfused and pump-perfused preparations of canine ileum, arterial pressure, venous outflow pressure, blood flow, and arteriovenous oxygen difference were measured while blood flow was altered either mechanically or by graded intra-arterial infusions of isoproterenol, adenosine, or 2,4-dinitrophenol. In pump-perfused preparations, mechanical alterations in blood flow resulted in opposite changes in arteriovenous oxygen difference, so that ileal oxygen uptake was independent of blood flow over the range of 30-140 ml.min-1.100 g-1. Only at flow rates below 30 ml.min-1.100 g-1 was oxygen uptake dependent on blood flow. Isoproterenol, adenosine, and dinitrophenol produced dose-dependent increases in blood flow under free-flow conditions and decreases in perfusion pressure under constant-flow conditions. Ileal oxygen uptake was not affected by isoproterenol, decreased by adenosine, and increased by dinitrophenol. The effects of these drugs on intestinal oxygen uptake are in accord with their effects on oxygen consumption in vitro. These results suggest that vasodilators will not alter intestinal oxygen uptake in autoperfused preparations in which oxygen uptake is independent of blood flow, unless they exert an effect on oxidative metabolism.
Human parotid saliva protein composition: dependence on physiological factors
Authors: Oberg S. G. , Izutsu K. T. , Truelove E. L.
Published: December 2017

The relative concentrations of the major proteins in human parotid saliva as measured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis varied greatly between the six individuals included in this study but were remarkably constant for a given individual. Individual relative parotid protein concentrations differed in salivas collected under unstimulated and stimulated conditions but were at least partially independent from circadian and feeding effects. In addition, the relative concentrations of certain salivary proteins decreased with continued lemon-drop stimulation. A total of 29 different bands was composited from the six subjects. Five of the bands had mobilities corresponding with those of calibration proteins selected for their known occurrence in parotid saliva. Only those proteins comprising at least 0.75% of the total protein concentration were detected. Relative protein concentrations of parotid saliva samples collected 12 mo apart from given individuals were identical.
Mucosal gastrin receptor. VII. Up- and downregulation
Authors: Speir G. R. , Takeuchi K. , Peitsch W. , Johnson L. R.
Published: December 2017

A series of experiments were performed to examine the long-term upregulation of the gastrin receptor and to explore the possibility of a short-term down regulation with regard to the time course of the trophic action of gastrin. Vagotomy or fasting was used to examine upregulation. Elevated serum gastrin levels observed postvagotomy are accompanied by an increase in gastrin binding capacity. Conversely, fasting caused a decline in serum gastrin and receptor levels; refeeding restored both values to normal levels. Cycloheximide was used to study the role of protein synthesis in the upregulation of gastrin receptors in vagotomized and refed rats, and it prevented the rise of gastrin binding capacity to either normal or above-normal values. This indicates that protein synthesis may play an integral part of receptor upregulation. Following the injection of gastrin-17, there was a short-term induction of downregulation. These results coupled with the maximal reduction of gastrin receptor 3 h after cycloheximide injection indicate that the gastrin receptor has a short half-life. Following the gastrin receptor interaction, the cellular response occurs at discrete periods and manifests itself as both down- and upregulation.
Mechanism of Cl- translocation across small intestinal brush-border membrane. II. Demonstration of Cl--OH- exchange and Cl- conductance
Authors: Liedtke C. M. , Hopfer U.
Published: December 2017

The mechanisms of Cl- transport across the brush-border membrane from rat small intestine were investigated in vitro in isolated vesicles and in vivo in ileal and jejunal segments. A Cl--OH- exchange mechanism was demonstrated in isolated vesicles by observing concentrative Cl- uptake driven by a pH gradient (extravesicular pH less than intravesicular pH). A Cl- conductance pathway was demonstrated by concentrative Cl- uptake driven by a K+ diffusion potential. The K+ diffusion potential was generated by a K+ concentration gradient in the presence of valinomycin (extravesicular K+ concentration greater than intravesicular K+ concentration). Furosemide and stilbene 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonate (SITS) strongly inhibited the Cl--OH- exchange but did not affect the Cl- conductance pathway, Na+-dependent glucose transport, and Na+-Na+ exchange. Under isotope exchange conditions at equilibrium, SITS inhibited Cl- transport up to 63%, indicating that this portion of Cl- transport is mediated by the Cl--OH- exchange transporter, with the remainder presumably due to the Cl- conductance pathway. In perfused small intestinal segments, Na+, Cl-, HCO3(-), and water were absorbed from the lumen in the absence of SITS. The presence of 5 mM SITS inhibited NaCl absorption and decreased HCO3(-) and water absorption in both jejunum and ileum but did not affect glucose absorption. The inhibition of in vivo salt absorption by SITS suggests that the Cl--OH- exchange mechanism plays a major role in NaCl absorption in intact enterocytes.
Determinants of biliary secretion in isolated perfused skate liver
Authors: Reed J. S. , Smith N. D. , Boyer J. L.
Published: December 2017

In the isolated perfused liver of the little skate, Raja erinacea, bile flow averaged 5.07 +/- 0.58 (mean +/- SE) microliters.h-1.g liver-1 in 21 experiments at a perfusion pressure of 5.0 cm Ringer compared to 3.79 +/- 0.32 in 38 experiments at 2.5 cm (P less than 0.05). [14C]inulin readily entered skate bile. Bile-to-plasma [14C]inulin ratios corrected for delay in transit time, averaged 0.46 +/- 0.07 at 1 h and rose to 0.74 +/- 0.06 by 4 h, although bile flow remained constant. In experiments in which [14C]inulin reached equilibrium between bile and plasma, the bile-to-plasma ratio conformed to the theoretical relationship between bile flow, solvent drag, and inert solute diffusion predicted at extremely low bile flows, but demonstrated that the skate biliary tree is more permeable to inulin than that of the rat. Electron microscopic studies demonstrated that ionic lanthanum could traverse the tight junctions. However, freeze-fracture studies of junction structure did not differ qualitatively from similar studies in the rat. Partial dependence of bile flow on perfusion pressure, high bile-to-plasma inulin ratios, and permeability of the canalicular tight junctions to ionic lanthanum all suggest that the paracellular pathway may be an important component of bile formation in the skate.
Effect of choleretics on canalicular transport of protoporphyrin in the rat liver
Authors: Avner D. L. , Berenson M. M.
Published: December 2017

The major route of protoporphyrin elimination is biliary secretion. To clarify the nature of the secretory process, maximal canalicular secretion of protoporphyrin was determined under basal conditions and after treatment with various choleretics. The maximal secretion of protoporphyrin under basal conditions was 0.07 +/- 0.01 micrograms.min-1.100 g body wt-1. Infusion of physiological amounts of sodium taurocholate increased protoporphyrin secretion 13-fold (0.90 +/- 0.02), primarily by increasing the biliary protoporphyrin concentration. Biliary protoporphyrin secretion tended to plateau in spite of a continued rise in both biliary bile acid secretion and concentration. Infusion of sodium dehydrocholate increased protoporphyrin secretion, but to only 35% of that achieved by sodium taurocholate. Ethacrynic acid and phenobarbital increased bile flow over controls but failed to enhance protoporphyrin transport. Thus, canalicular secretion of protoporphyrin was maximally enhanced by micelle-forming bile acids and unaffected by nonbile acid choleretics. The observed limitation of protoporphyrin secretion may be related to achievement of a canalicular transport maximum or to a toxic effect of protoporphyrin on the transport process.
Escherichia coli heat-stable toxin: its effect on motility of the small intestine
Authors: Mathias J. R. , Nogueira J. , Martin J. L. , Carlson G. M. , Giannella R. A.
Published: December 2017

Escherichia coli heat-stable enterotoxin is a low-molecular-weight substance that has been shown to induce the active secretion of fluid and electrolytes in the small intestine. In this study, we have characterized the effects of purified E. coli heat-stable toxin (ST, strain 18D, serotype 042:K86:H37) on the motility of rabbit small intestine by using myoelectric recording techniques. Substances, such as cholera toxin, that activate the adenylate cyclase-cAMP system induced predominantly migrating action-potential complex activity. E. coli ST, a toxin that activates the guanylate cyclase-cGMP system, was infused into isolated in vivo ileal loops of New Zealand White rabbits. Inactivated toxin was also studied by exposing the ST to 1 mM dithiothreitol for 90 min. Active E. coli ST induced only repetitive bursts of action potentials. When the toxin was inactivated with dithiothreitol, no alteration in myoelectric activity was observed. We speculate that repetitive bursts of action-potential activity may represent a virulent factor of the bacterium, altering motor activity to slow transit and allowing for bacterial proliferation and invasion.
Receptors on smooth muscle cells: characterization by contraction and specific antagonists
Authors: Bitar K. N. , Makhlouf G. M.
Published: December 2017

Smooth muscle cells were isolated from the stomach of the guinea pig, and the kinetics, stoichiometry, and specificity of contraction in response to the C-terminal octapeptides of cholecystokinin (CCK-OP), gastrin-17, and acetylcholine were examined. All three agonists elicited dose-dependent peak contraction that did not depend on the presence of extra-cellular calcium. The potencies of CCK-OP and gastrin-17 were equal (D50, 10(-11) M) and 10 times greater than the potency of acetylcholine (D50, 10(-10) M). A combination of low doses of acetylcholine and CCK-OP was synergistic; however, its effect did not exceed the maximal responses to either agonists alone or to high extracellular concentrations of calcium. The specificity of the receptors was established by the use of atropine and the two CCK-receptor antagonists dibutyryl cGMP and proglumide. The span of the dose-response curves was wide, suggesting the existence of receptor heterogeneity. It is concluded that gastric smooth muscle cells of the guinea pig possess distinct, high-affinity receptors for CCK-gastrin and acetylcholine; the receptors mediate contraction that is not immediately dependent on the presence of extracellular calcium.
Maximal lymphatic triglyceride transport rate from the rat small intestine
Authors: Tso P. , Buch K. L. , Balint J. A. , Rodgers J. B.
Published: December 2017

In previous studies, we demonstrated that the hydrophobic surfactant Pluronic L-81 blocks lymphatic triglyceride transport from the small intestine and leads to accumulation of triglyceride in the mucosa. The onset of action of Pluronic L-81 is rapid and quickly reversed once its administration is discontinued. We have taken advantage of these effects of Pluronic L-81 on intestinal lipid transport in order to determine the apparent maximal triglyceride transport capacity of the proximal half of the rat small bowel using lymph fistula rats infused intraduodenally with a phosphate-buffered, taurocholate-stabilized emulsion containing 40 mumol [3H]triolein and 0.5 mg Pluronic L-81 at 3 ml/h for 8 h to load the proximal small bowel with lipid. Studies were done in one group of rats in order to be certain that only the proximal half of the small bowel contained 3H-lipid after this period of infusion. In other rats treated similarly, the 8 h of lipid-Pluronic L-81 infusion were followed by infusion of 3 ml/h of 0.15 M salt solution for 5 h. Lymphatic transport of lipid was determined throughout the entire period of infusion. During lipid-Pluronic L-81 infusion, transport of 3H-triglyceride fatty acid into lymph was only 22-27 mumol/h but rose steadily after substitution of saline and reached a maximal transport rate of 109 +/- 6.2 mumol/h (means +/- SE) after 3.5 h. During this 3.5-h period, the amount of 3H-lipid in the proximal mucosa declined from 530 to 263 mumol. While Pluronic L-81 was infused, only very low-density-lipoprotein-sized particles were seen in lymph by electron microscopy, whereas, at the peak of triglyceride transport during saline infusion, chylomicrons of up to 6,000 A were observed in lymph.
Effect of ethanol on peptidases of hamster jejunal brush-border membrane
Authors: Dinda P. K. , Beck I. T.
Published: December 2017

This study was undertaken to investigate the effect of ethanol on the brush-border activity of the small intestine. Brush-border membrane isolated from hamster jejunum was incubated with L-phenylalanylglycine (Phe-Gly), L-leucylglycine (Leu-Gly), or glycyl-L-tyrosine (Gly-Tyr) in the absence and presence of 1-5% (wt/vol) ethanol, and the L-amino acids liberated were determined. Ethanol was found to depress the hydrolysis of all peptides in a dose-dependent manner. The inhibitory effect of ethanol on the peptidases does not appear to be time dependent. The ethanol-induced inhibition of peptidase activity is completely reversible. Kinetic studies indicate that ethanol caused a decrease in the Vmax of the enzymes responsible for the hydrolysis of the Phe-Gly and Gly-Tyr but did not have any effect on their Km. In the hydrolysis of Leu-Gly, two enzymes were involved, and ethanol depressed the Vmax of both without affecting the Km of either. These findings suggest that ethanol produces conformational changes of the peptidases involved in the hydrolysis of these three dipeptides.
Gastrin and growth of the alimentary tract in the streptozotocin-diabetic rat
Authors: Schedl H. P. , Wilson H. D. , Ramaswamy K. , Lichtenberger L.
Published: December 2017

Mucosal growth in small intestine of the streptozotocin-diabetic rat is increased; insulin treatment decreases growth toward normal. Gastrin is trophic to the alimentary tract. Therefore, we measured gastrin and growth of the alimentary tract in controls, diabetics, and insulin-treated diabetics. Mucosal growth of the small intestine increased at 10 days of diabetes and increased further by 20 days. Serum and antral gastrin did not respond to diabetes at 10 days. At 20 days, mean antral gastrin was increased in all diabetic groups, but the increase was significant only for a hyperphagic ad libitum-fed diabetic group, which also showed increased serum gastrin. Insulin treatment decreased serum gastrin but only partly reversed the increased mucosal growth in diabetics. We conclude that 1) gastrin is not the primary cause for increased small intestinal mucosal growth in diabetes, inasmuch as gastrin did not respond to diabetes at 10 days when mucosal growth was increased, and decreased serum gastrin in insulin-treated groups was associated with increased mucosal growth; and 2) diabetes appears to increase gastrin.
Actions of Gila monster venom on dispersed acini from guinea pig pancreas
Authors: Raufman J. P. , Jensen R. T. , Sutliff V. E. , Pisano J. J. , Gardner J. D.
Published: December 2017

Venom from Gila monster (family Helodermatidae) contains a pancreatic secretagogue. In dispersed acini from guinea pig pancreas, the venom increased enzyme secretion to the same extent as did vasoactive intestinal peptide, secretin, or PHI. The abilities of vasoactive intestinal peptide and Gila monster venom to stimulate enzyme secretion were not altered by boiling but were abolished by incubation with trypsin or chymotrypsin. Like vasoactive intestinal peptide, secretin, and PHI, the venom caused a 50- to 60-fold increase in cellular cAMP and inhibited binding of 125I-vasoactive intestinal peptide to its membrane receptors on pancreatic acini. The action of venom on enzyme secretion was inhibited by [Gln9]secretin-(5-27), a vasoactive intestinal peptide receptor antagonist, but was not altered by atropine, a cholinergic receptor antagonist, or by dibutyryl cGMP, a cholecystokinin receptor antagonist. Gila monster venom contained no immunoreactive vasoactive intestinal peptide by radioimmunoassay. These results indicate that venom from Gila monster contains a peptide that can stimulate pancreatic enzyme secretion by interacting with vasoactive intestinal peptide receptors on pancreatic acinar cells and thereby activating adenylate cyclase and increasing cellular cAMP.
beta 1- and beta 2-adrenoceptor agonists have different effects on rat parotid acinar cells
Authors: Henriksson R.
Published: December 2017

To determine whether beta 1- and beta 2-adrenoceptors have similar functions in salivary glands, Sprague-Dawley rats were chronically treated with either the beta 1-selective (prenalterol), beta 2-selective (terbutaline), or the nonselective beta-agonist isoproterenol. All three agonists increased parotid and submandibular gland weight and acinar cell size. Isoproterenol and prenalterol caused marked quantitative and qualitative alterations in the granule population, whereas terbutaline had no effect. A single injection of isoproterenol caused a significant amylase release and accumulation of cAMP. Prenalterol was as potent as isoproterenol with regard to amylase release but was without effect on the cAMP content. In contrast, terbutaline had a minimal effect on amylase release but had the same effect as isoproterenol on cAMP accumulation. The in vitro perifusion experiments confirmed these in vivo results with respect to the effects of the selective beta-agonists. Thus, the present investigation using both morphological and biochemical methods suggests that beta 1- and beta 2-adrenoceptors may have different functions in rat parotid acinar cells. In addition, the stimulus-growth coupling seems to be unrelated to stimulus-secretion coupling.
Effect of acute respiratory alkalosis and acidosis on intestinal ion transport in vivo
Authors: Feldman G. M. , Charney A. N.
Published: December 2017

The effects of acute respiratory alkalosis and acidosis on intestinal electrolyte transport were studied in adult Sprague-Dawley rats. During in situ intestinal perfusion, anesthetized animals were ventilated with 0, 3, or 8% CO2, creating states of alkalosis (pH 7.64 +/- 0.01), normocapnia (pH 7.45 +/- 0.01), or acidosis (pH 7.26 +/- 0.01), respectively. The plasma bicarbonate concentration decreased 2.0 mM during alkalosis and increased 2.1 mM during acidosis. The jejunum did not respond to the acid-base disturbances. In both the ileum and colon, alkalosis decreased the net absorption of water (-16%), sodium (-23%), and chloride (-42%) and the net secretion of bicarbonate (-33%), whereas acidosis had the opposite effect, i.e., the net absorption of water (41%), sodium (39%), and chloride (32%) increased as did net bicarbonate secretion (33%) (ileal values given). Changes in sodium chloride movement could be correlated with changes in systemic pH and CO2 tension (PCO2), and bicarbonate secretion paralleled changes in the plasma bicarbonate concentration. The acid-base disorders had no effect on ileal and colonic net potassium secretion and transmural potential difference. These studies suggest that systemic pH and/or PCO2 regulate sodium chloride absorption, and the plasma bicarbonate concentration regulates bicarbonate secretion.
Metabolism of arachidonic acid by pancreatic acini: relation to amylase secretion
Authors: Stenson W. F. , Lobos E.
Published: December 2017

Isolated guinea pig pancreatic acini were incubated with exogenous [14C]arachidonic acid (10 microM) at 37 degrees C for 3 min. The lipids were extracted and separated by thin-layer chromatography. Radiolabeled metabolites were identified by comigration with standards: 0.024% of the recovered radioactivity comigrated with prostaglandin E2 (PGE2), 0.016% comigrated with PGF2 alpha, 4.9% was incorporated into triglycerides, 1.8% was incorporated into phospholipids, and 93.2% remained as arachidonic acid. The synthesis of PGE2 and PGF2 alpha was inhibited by indomethacin (ID50, 30 nM). Simultaneous addition of carbachol or caerulein with the [14C]arachidonic acid did not alter the metabolism of the arachidonate. Further studies were done on the role of arachidonate metabolites in the secretion of amylase. Exogenously added PGE2 and PGF2 alpha (0.3-100 nM) did not induce amylase secretion from isolated acini. Incubation of isolated acini with indomethacin (0.1-28 microM) did not inhibit the release of amylase induced by carbachol or caerulein. From these data, we conclude that isolated guinea pig pancreatic acini are capable of converting a small percentage of exogenous arachidonate to PGE2 and PGF2 alpha. However, there is no evidence for a role of these compounds in stimulus-secretion coupling.
Regulation of oxygen uptake in resting and pentagastrin-stimulated canine stomach
Authors: Perry M. A. , Bulkley G. B. , Kvietys P. R. , Granger D. N.
Published: December 2017

The relation between oxygen uptake and blood flow in the isolated dog stomach was investigated under resting conditions and during intra-arterial infusion of isoproterenol or pentagastrin. Blood flows above and below control values were achieved by pump perfusion and partial arterial occlusion, respectively. In the resting stomach oxygen uptake increased from 0.4 to 1.5 ml.min-1.100 g-1 as blood flow increased from 4 to 40 ml.min-1.100 g-1 and then remained constant for blood flows up to 100 ml.min-1.100 g-1. Isoproterenol did not significantly alter the relation between oxygen uptake and blood flow. In pentagastrin-stimulated stomachs oxygen uptake was maintained at 2.5 ml.min-1.100 g-1 at blood flows between 40 and 100 ml.min-1.100 g-1 and decreased at blood flows below 40 ml.min-1.100 g-1. The results indicate that pentagastrin increases oxidative metabolism in the stomach. Despite this increase in oxygen consumption with pentagastrin, the general shape of the relation between blood flow and oxygen uptake remained the same and was simply displaced vertically above the control data.
Gastric vascular actions of prostanoids and the dual effect of arachidonic acid
Authors: Kauffman G. L. , Whittle B. J.
Published: December 2017

The effects of several prostanoids and arachidonic acid on gastric vascular perfusion pressure were studied in dogs. A chambered segment of gastric fundus in anesthetized, heparin-treated dogs was perfused at constant flow (10 ml.min-1) with femoral arterial blood. Changes in perfusion pressure were measured after intra-arterial injection of each agent, at a point from which it reached the stomach in 3 s. Prostacyclin, prostaglandin E2 (PGE2), and PGE1 (5-40 ng) reduced perfusion pressure by 10-35 mmHg and were equipotent. 6-oxo-PGE1, the endoperoxide PGH2, and two stable prostacyclin analogues carbacyclin and 6 beta-PGI1 were less potent vasodilators, whereas 6-oxo-PGF1a was inactive. The epoxymethano endoperoxide analogues (U-46619 and U-44069) were equipotent vasoconstrictors, doses of 10-100 ng causing increases in perfusion pressure of 10-35 mmHg. PGF2a and noradrenaline also had vasoconstrictor actions. PGD2 had inconsistent actions. The effect of arachidonic acid on perfusion pressure varied with the length of time in contact with blood. Close (3 s incubation) intra-arterial injection (25-200 micrograms) produced vasodilation, whereas distal intra-arterial injection, which allowed 30 s of contact with blood before reaching the stomach, produced vasoconstriction as evidenced by dose-related increases in perfusion pressure (10-65 mmHg). These observations suggest that arachidonic acid, given by close intraarterial injection, is converted in the stomach mainly to vasodilator substances, presumably PGI2 or PGE2, but is converted mainly to a vasoconstrictor substance, presumably thromboxane A2, when allowed to mix with blood for 30 s.
Mechanism of cycling of migrating myoelectric complexes: effect of morphine
Authors: Sarna S. , Northcott P. , Belbeck L.
Published: December 2017

Morphine was injected intravenously at various phases of the migrating myoelectric complex (MMC) cycle to study the oscillatory characteristics of MMCs by the premature initiation of phase IIIs. All injection timings were represented as a percentage of the normal MMC period at the most proximal duodenal electrode. During the initial 20% of the MMC cycle, the mechanism of initiation of MMCs was in an absolutely refractory state in the sense that a supramaximal dose of morphine (200-300 micrograms/kg) did not initiate a premature phase III. During the remainder of the MMC cycle, the control mechanism was in a relatively refractory state. As this state progressed, premature phase III activity was initiated with diminishing doses of morphine. This was called the relatively refractory state. The initiation of a premature phase III by morphine did not affect the phase III already in progress, except that its propagation velocity was increased. Truncal vagotomy did not affect the refractory characteristics of MMCs or the action of morphine. Only large doses of naloxone (2 mg/kg) blocked the above action of morphine. The study shows that the MMC cyclic phenomenon has the characteristics of relaxation oscillators that may result from enteric neural biological clocks. The period of these oscillators can be altered by stimulants such as morphine.
Pancreatic circulation: intrinsic regulation
Authors: Kvietys P. R. , McLendon J. M. , Bulkley G. B. , Perry M. A. , Granger D. N.
Published: December 2017

The purpose of the present study was to characterize the intrinsic mechanisms involved in the regulation of blood flow and oxygenation in the totally isolated, perfused canine pancreas. Arterial pressure, venous outflow pressure, blood flow, arteriovenous oxygen difference, and capillary filtration coefficient were measured during graded arterial pressure reductions and venous pressure elevation. Reductions in arterial pressure caused pancreatic blood flow and vascular resistance to decrease, whereas venous pressure elevation resulted in a decreased blood flow and increased vascular resistance. The reductions in blood flow produced by arterial and venous pressure alterations were associated with increases in oxygen extraction and capillary filtration coefficient. During the same pressure perturbations, oxygen uptake remained constant between blood flows of 40-100 ml.min-1.100 g-1, yet decreased progressively as blood flow was reduced below 40 ml.min-1.100 g-1. Arterial occlusion resulted in a postocclusive reactive hyperemia, the magnitude of which was related to the duration of occlusion. The findings of this study suggest that intrinsic regulation of pancreatic blood flow can be attributed to both metabolic and myogenic mechanisms. Resistance and exchange vessels both appear to play a role in the regulation of oxygen delivery to the pancreatic parenchyma.
Chloride transport by intact rat liver and cultured rat hepatocytes
Authors: Scharschmidt B. F. , Van Dyke R. W. , Stephens J. E.
Published: December 2017

Chloride is the predominant inorganic anion in bile, and it has been proposed that active chloride transport, possibly via a sodium-coupled mechanism, may contribute to that portion of canalicular bile formation not directly related to bile acid transport (bile acid-dependent bile formation or BAIBF). We have therefore examined the anion specificity of BAIBF using the isolated perfused rat liver and have studied sodium-chloride flux coupling and the sodium dependence of intracellular chloride content using 22Na and 36Cl transport by cultured rat hepatocytes. BAIBF by the isolated rat liver was unaltered by replacement of chloride with nitrate or benzenesulfonate but was significantly reduced by replacement of chloride with sulfate or thiocyanate. In cultured hepatocytes, sodium entry rate was reduced when chloride in the incubation medium was replaced by cyclamate, benzenesulfonate, or sulfate and mannitol but was unaffected when chloride was replaced by nitrate, gluconate, or thiocyanate. Conversely, chloride entry rate was decreased when sodium was replaced with choline but was unaffected when sodium was replaced by lithium or when ouabain was added to the medium. Thus no consistent evidence of sodium-chloride flux coupling was observed. Steady-state exchangeable intracellular chloride in the cultured hepatocytes was unaffected by ouabain or by replacement of sodium with choline and was increased when sodium was replaced by lithium. These findings indicate that basal BAIBF exhibits no specific chloride requirement. Although they do not exclude the possible existence in rat liver of sodium-coupled chloride transport, they provide no evidence that such a mechanism accounts for a major portion either of chloride transport by individual rat hepatocytes or of basal BAIBF by intact rat liver.
Incremental and decremental kinetics of gastric responses to infused gastrin in dogs
Authors: Hirschowitz B. I.
Published: December 2017

Acid and pepsin secretion was stimulated by graded doses of synthetic human gastrin I (G-17-I) and pentagastrin (G-5) in six conscious gastric fistula dogs, three with intact vagi and three with fundic vagotomy. Metabolic clearance rate of G-17 was 15.2 ml.kg-1.min-1 and volume of distribution was 15.8%. Gastrin levels decayed in two slopes: t1/2 of 6.8 min and 25-35 min, respectively. These were compared with other published data. Vmax was higher in intact stomachs and at doses or blood levels of gastrin about three to four times smaller. G-17 was almost four times more potent (molar basis) than G-5. Responses were log linearly related to G-17 dose and to serum G-17 during infusion (incremental) and after stopping infusion (decremental). Normalized decremental curves were congruent in all dogs but displaced fivefold (625 vs. 130 pmol/l) to the right at midpoint. Vagotomy changed only association (incremental) kinetics (Km = 352 pmol/l). The previously undescribed difference between blood concentration-effect relationship during drug administration and withdrawal may be important in situations in which blood levels are used as therapeutic guide.
Role of gastrin in gastrointestinal adaptation after small bowel resection
Authors: Dembinski A. B. , Johnson L. R.
Published: December 2017

Gastrin is a trophic hormone for the mucosa of the oxyntic gland area of the stomach, the proximal small intestine, and the colon. It also has trophic effects on the pancreas. All these tissues undergo hyperplasia to some extent following distal small bowel resection. This study evaluates the role of gastrin in postresectional hyperplasia by examining the growth of these tissues in antrectomized rats following intestinal resection. Antrectomy itself caused atrophy of the oxyntic gland mucosa, colonic mucosa, and the pancreas but had no effect on ileal mucosa. Resection by itself stimulated growth of all tissues and significantly increased serum gastrin levels. After resection in antrectomized animals, all tissues underwent an adaptational response. The increase in total DNA content after resection in antrectomized rats was as great in all tissues, except the colon, as it was in animals with intact antrums and normal gastrin levels. These results indicate that gastrin plays no role in the postresectional hyperplasia observed in the various tissues of the gastrointestinal tract.
Effect of liquid meals on duodenogastric reflux in humans
Authors: Sonnenberg A. , Muller-Lissner S. A. , Weiser H. F. , Muller-Duysing W. , Heinzel F. , Blum A. L.
Published: December 2017

In humans duodenogastric reflux and gastric emptying were measured simultaneously by a two-marker technique that avoids transpyloric intubation. The duodenal marker consisted of 99mTc-labeled Hepatobida and was infused intravenously at a constant rate. Hepatobida was cleared almost exclusively by the liver and entered the duodenum at a constant rate via the bile. The gastric marker consisted of 51CrCl2 and was used to measure total intragastric volume by the double-sampling technique. Duodenogastric reflux occurred both after meals and under fasting conditions. Reflux rate was on the average 13 times smaller than emptying rate. It was higher with a lipid than with a protein meal and was independent of the rate of gastric emptying. The gastric concentration and total amount of duodenal contents were higher after lipid than protein meals. Since gastric emptying of a protein meal was faster than emptying of a lipid meal, the increased gastric concentration and accumulation of duodenal contents after lipid meals are due to a slowed gastric clearing and increased reflux of duodenal contents. Under fasting conditions, the reflux was lower and the gastric concentration of duodenal contents was higher than with both types of meals. Hence regurgitated duodenal contents may cause more damage to the gastric mucosa under fasting conditions than postprandially.
Regulation of pancreatic protein synthesis by cholecystokinin and calcium
Authors: Korc M.
Published: December 2017

The effect of cholecystokinin (CCK) on [3H]phenylalanine and [14C]tyrosine incorporation into protein was studied in isolated rat pancreatic acini. CCK8, the biologically active octapeptide of CCK, had a biphasic effect on amino acid incorporation. The magnitude of the stimulatory effect (maximal at 10(-10) to 3 X 10(-10) M CCK8) was greater in diabetic rats, whereas the magnitude of the inhibitory effect (maximal at 10(-8) M CCK8) was greater in normal rats. Omission of extracellular Ca2+ from the incubation media did not diminish the stimulatory action of CCK8. Addition of 10(-4) M EGTA to media containing no added Ca2+ lowered basal incorporation, abolished CCK's stimulatory effect and enhanced its inhibitory effect. Stimulation was restored in the presence of Ca2+. The stimulatory effect of the cholinergic analogue carbachol (10(-5) M) on amino acid incorporation was also abolished by removal of extracellular Ca2+, whereas the stimulatory effect of insulin (1.67 X 10(-8) M) remained intact. These findings suggest that CCK and other pancreatic secretagogues enhance pancreatic protein synthesis via Ca2+, whereas stimulation by insulin occurs via another mechanism.
Does calcium mediate the slowing of gastric emptying in primates?
Authors: Hunt J. N. , McHugh P. R.
Published: December 2017

Disodium edetate (EDTA, 1 g/l) in test meals of water slowed gastric emptying strongly in one human and in four rhesus monkeys. When the binding sites of the EDTA were loaded with calcium before it was given in the test meal, there was little effect on gastric emptying. It is suggested that EDTA takes up calcium from the “tight junctions” of the duodenal epithelium. As a result a signal is set up that slows gastric emptying. It is postulated that the anions of fatty acids produced during the digestion of triglycerides in the duodenum also slow gastric emptying by the same mechanism. We explain how fats, carbohydrates, and proteins could all slow gastric emptying by operating on the same receptor.
Does Na+-K+-atpase have any role in bile secretion?
Authors: Erlinger S.
Published: December 2017

In this review, I have attempted to summarize the evidence supporting the view that Na+-K+-ATPase (the enzymatic basis for the sodium pump) plays a key role in bile secretion. First, experiments in the isolated perfused liver, in isolated and cultured hepatocytes, and more recently in hepatocyte membrane vesicles strongly suggest that bile acid uptake by the hepatocyte is a secondary active transport that is energized by the Na+ gradient maintained by the Na+-K+-ATPase. Thus, Na+-K+-ATPase appears important in coupling the energy from ATP to transport activity, resulting in the so-called bile acid-dependent bile flow. Second, experiments with liver plasma membranes have shown a correlation between Na+-K+-ATPase activity in these preparations and the so-called bile acid-independent bile flow. In view of the recognized sinusoidal-lateral localization of the Na+-K+-ATPase in the liver cells, several possibilities are proposed to explain how the enzyme activity could be coupled to ion transport and secretion into bile. These possibilities include Na+ movement from the intercellular space into the canalicular lumen through the paracellular pathway and movement of another ion using the Na+ gradient.
Role of histamine H1- and H2-receptors in postprandial intestinal hyperemia
Authors: Chou C. C. , Siregar H.
Published: December 2017

Studies were conducted in anesthetized dogs to assess whether histamine H1- and/or H2-receptors play a role in post-prandial intestinal hyperemia. The vascular and metabolic responses of jejunal segments to intra-arterial infusion of histamine and luminal placement of food before and after administration of tripelennamine, an H1-receptor antagonist, metiamide, an H2-receptor antagonist, and the combination of both antagonists were compared. Administration of the antagonists had no effect of jejunal blood flow and intestinal oxygen uptake (VO2). Tripelennamine or metiamide alone attenuated while the combination of both blocked the histamine-induced increases in blood flow and VO2. Metamide alone had no effect on the food-induced increases in flow and VO2. Tripelennamine significantly attenuated the food-induced increase in flow and blocked the increase in VO2. A 30% increase in flow was reduced to 15% after tripelennamine. The effects of tripelennamine plus metiamide were statistically the same as those of tripelennamine alone. It is concluded that endogenous histamines may play a role in postprandial intestinal hyperemia, and the effect is primarily mediated by the H1-receptors.
Aminopyrine accumulation by mammalian gastric glands: an analysis of the technique
Authors: Sack J. , Spenney J. G.
Published: December 2017

Isolated gastric glands from rabbits and parietal cells from dogs have recently become useful in studying the control and enzymatic mechanisms of gastric H+ secretion. The present studies were performed to determine the experimental variables that account for widely differing aminopyrine accumulation reported in various publications. We found that two principle factors were responsible for wide differences in aminopyrine accumulation. First, we found that commercially available aminopyrine contained an unidentified impurity that increased with storage. A procedure for purification is included. The contaminant is not accumulated in secreting gastric glands and thereby reduces the aminopyrine ratio that can be achieved. Mixing of glands appeared to be the second important variable. It was found that incubation in 1.5-ml capped conical polypropylene centrifuge tubes in the horizontal position with shaking in the long axis of the tubes gave aminopyrine ratios that were more than double the results obtained by other mixing techniques. In addition a gland density of 1--2 mg dry wt/ml glands and a mixing rate of 110 cycles/min gave the best results. Calculations indicate that, at high gland densities, even modest amounts of impurity in the aminopyrine will significantly reduce aminopyrine ratios. With optimal conditions our greatest aminopyrine ratio was 1,050, which suggests an H+ concentration of approximately 67 mM in the canaliculi and tubulovesicular membrane system of the parietal cell. Such a level of function approaches that of the intact in vivo organ.
Comparison of binding and removal of remnants of triglyceride-rich lipoproteins of intestinal and hepatic origin by rat liver in vitro
Authors: Cooper A. D. , Shrewsbury M. A. , Erickson S. K.
Published: December 2017

Chylomicrons were isolated from intestinal lymph and very low-density lipoproteins (VLDL) from the perfusate of isolated perfused livers. In vivo the initial phase of clearance of these particles was very rapid. Chylomicrons appeared to be cleared more quickly than VLDL (t1/2 = 3.7 +/- 1.4 vs. 10.6 +/- 4.0 min). Remnants were prepared from these particles in eviscerated rats and isolated using conditions under which contamination of particles from one organ by particles from the other organ was minimal. The removal of these remnant particles by isolated perfused livers was studied. VLDL remnants were removed more rapidly than the nascent VLDL. The removal of 125I-labeled VLDL remnants was inhibited by the presence of unlabeled VLDL remnants or chylomicron remnants in the perfusate. A 15- to 20-fold excess of either particle inhibited about 50% of the uptake of the labeled lipoprotein. The two types of remnants had comparable potency as competitors of uptake. Similarly, the two types of remnants inhibited uptake of a trace of labeled chylomicron remnants. The binding of these particles to rat liver plasma remnants. The binding of these particles to rat liver plasma membranes was also investigated. Both labeled chylomicron remnants and VLDL remnants bound specifically to the membranes, and either type of remnant displaced the binding of the other with equal potency. Taken together, these results indicate that chylomicron and VLDL remnants share the same hepatic removal mechanism and suggest that the rate of removal of a remnant is not a function of the organ of origin of the precursor lipoprotein.
Cholecystokinin-induced contraction of dispersed smooth muscle cells
Authors: Collins S. M. , Gardner J. D.
Published: December 2017

Isolated smooth muscle cells were prepared from the fundus of guinea pig stomach by incubation with collagenase. Incubating the cells with the C-terminal octapeptide of cholecystokinin induced contraction, which was measured by micrometry and expressed as percent decrease in mean cell length. Cholecystokinin-induced contraction was maximal within 30 s and reduced cell length by approximately 37%. The threshold concentration of cholecystokinin was 0.1 pM, and the maximally effective concentration was 0.3 nM. Contraction caused by cholecystokinin could be inhibited by proglumide and by glucagon. Inhibition by proglumide was competitive and resulted in a parallel rightward shift of the cholecystokinin dose-response curve. In contrast, inhibition by glucagon was noncompetitive and resulted in a reduction in the efficacy of cholecystokinin without a change in its potency. Furthermore, proglumide-induced inhibition was specific for cholecystokinin, whereas glucagon-induced inhibition of contraction was nonspecific and reduced the contraction caused by carbamylcholine and the calcium ionophore A23187.
Inhibition of acid secretion in isolated gastric glands by substituted benzimidazoles
Authors: Fellenius E. , Elander B. , Wallmark B. , Helander H. F. , Berglindh T.
Published: December 2017

A new class of gastric acid inhibitors, substituted benzimidazoles (H 83/69 and H 149/94), have been tested in an isolated rabbit gastric gland preparation. Acid formation in the glands was stimulated by histamine, dibutyryl cAMP (DBcAMP), and high extracellular K+ concentrations, and the glandular secretory response was measured by changes in oxygen consumption and in accumulation of the weak base [14C]aminopyrine (AP). The substituted benzimidazoles inhibited AP accumulation induced by all stimulants in a dose-dependent noncompetitive manner. In contrast, cimetidine only inhibited histamine-induced AP accumulation. Basal AP accumulation, not affected by cimetidine, was also inhibited by the substituted benzimidazoles, as was the increase in glandular oxygen consumption produced by the addition of histamine and DBcAMP. Basal oxygen consumption was inhibited by about 15%. The substituted benzimidazoles, like AP, are weak bases and were also found to accumulate in the glands. Semiquantitative morphological studies of glands stimulated by histamine plus theophylline did not show any change in the enlarged secretory surface area after stimulation in the presence of inhibitory concentrations of H 149/94 (10(-4) M). The results suggest that substituted benzimidazoles have a mechanism of action different from that of H2-receptor antagonists and indicate a very distal site of action in the events leading to acid formation.