bluuebunny/crossref_metadata_2025 huggingface dataset:
Protective effects of prostaglandins against gastric mucosal damage: current knowledge and proposed mechanisms
Authors: Miller T. A.
Published: December 2017

Recent evidence indicates that prostaglandins (PGs) possess potent gastric antiulcer properties independent of their known inhibitory effects on acid secretion. The mechanism underlying this cytoprotective property, as it has been called, has remained elusive. Although exogenously administered PGs can prevent disruption of the gastric mucosal barrier, enhance gastric mucosal blood flow, and stimulate mucus and bicarbonate secretion, as well as a number of cellular transport processes, evidence for and against each of these proposed mechanisms for cytoprotection has been demonstrated. Thus, it is doubtful whether any of these effects of PGs on gastric epithelium is the mechanism responsible for cytoprotection, if indeed a single, common mechanism exists. In addition, an association between alterations in endogenous PGs and gastric mucosal injury induced by a variety of damaging agents has also been observed, but the importance of this association in terms of mediating gastric damage needs further clarification. Finally, the phenomenon of adaptive cytoprotection in which mild irritants protect the gastric mucosa against the damaging effects of various necrotizing agents may also be PG mediated since it can be blocked by indomethacin, an inhibitor of PG synthesis, but a clear association between changes in endogenous PGs and adaptive cytoprotection remains to be demonstrated. Despite being inconclusive, these findings suggest that PGs may play a significant role in the pathogenesis of gastric ulceration and may serve an important function in maintaining normal gastric mucosal integrity.
Activity fronts in fed dogs: effect of a beta-adrenergic agonist
Authors: Yanda R. , Summers R. W.
Published: December 2017

The effect of the beta-adrenergic agonist isoproterenol on intestinal myoelectric activities was studied in fed dogs. A 15-min isoproterenol infusion (0.5 micrograms X kg-1 X min-1) initiated activity fronts after a meal in 14 of 16 experiments. The phase III motor activity was of similar duration and migrated aborally at the same rate as spontaneous fronts occurring in the interdigestive period; however, the activity fronts usually originated in the midjejunum and seldom migrated to the terminal ileum. The isoproterenol-induced fronts were blocked by pretreatment with propranolol (1 mg/kg). Activity fronts were not induced by sodium nitroprusside (10 micrograms X kg-1 X min-1), even though it inhibited myoelectric activity and induced hypotension and tachycardia to a degree similar to that caused by isoproterenol. The effects of isoproterenol were not blocked by vagotomy. Longer isoproterenol infusions of 2 h produced one but not more activity fronts and infusions in the fasted state did not induce premature fronts. These results do not support the hypothesis that the effect of isoproterenol is due to a neural reflex, and further studies are necessary to determine which of several potential mechanisms is responsible for this effect.
Effect of transport inhibitors on secretion by perfused rat submandibular gland
Authors: Martinez J. R. , Cassity N.
Published: December 2017

Ouabain (10(-3) M) caused a 95.8% reduction in the volume of saliva secreted during a 60-min period by the isolated, perfused submandibular gland of the rat exposed to acetylcholine (10(-6) M) and modified salivary cation (Na and K) concentrations but not salivary Cl concentrations. Furosemide (10(-3) M) caused a 74.9% reduction in saliva volume and significantly reduced salivary Cl concentrations but did not modify salivary Na or K. Ethacrynic acid (10(-4) M) resulted in a 58.6% reduction in saliva volume, increased salivary Na and Cl concentrations, and reduced salivary K+ concentrations at low rates of flow. The results suggest that an ouabain-sensitive Na+-K+-ATPase and a furosemide-sensitive NaCl cotransport system contribute to acetylcholine-induced fluid secretion in the rat submandibular gland. The Na+-K+-ATPase probably provides the energy or driving force for the NaCl cotransport system by maintaining a Na+ gradient in the salivary cells. The lesser effect of ethacrynic acid on saliva volumes may result from a quantitatively smaller action on the same NaCl cotransport affected by furosemide. An ouabain-sensitive pump present in salivary ducts regulates transductal transport of Na and K.
Dantrolene and basal ileal sodium and chloride transport: involvement of calcium stores
Authors: Donowitz M. , Cusolito S. , Battisti L. , Sharp G. W.
Published: December 2017

The effect of dantrolene on active ion transport in rabbit ileum was determined using the Ussing chamber short-circuiting technique. Dantrolene prevents the release of calcium from intracellular stores in skeletal muscle and was used to probe the role of intracellular calcium stores in intestinal ion transport. A saturated solution of dantrolene (approx 25 microM) decreased ileal short-circuit current and potential difference, increased conductance and mucosal-to-serosal and net Na and Cl fluxes, but did not alter serosal-to-mucosal Na and Cl fluxes. The dantrolene stimulation of active Na and Cl absorption was specific since it did not alter glucose-dependent Na absorption, transport changes caused by Ca2+ ionophore A23187, or the increase in short-circuit current caused by dibutyryl cAMP or theophylline. These effects were associated with an increase in total ileal calcium content and a decreased rate of 45Ca2+ efflux without any change in 45Ca2+ influx from the serosal or mucosal surfaces. These findings are consistent with an effect of dantrolene to stimulate active ileal Na and Cl absorption by a mechanism involving lowered cytosol Ca2+ levels and compatible with trapping calcium in intracellular stores. It thus appears as if intracellular calcium stores have an important role in the control of basal ion transport in the intestine.
Systems analysis of intestinal hemodynamics and oxygenation
Authors: Granger D. N. , Granger H. J.
Published: December 2017

A systems analysis of intrinsic regulation of intestinal blood flow and oxygenation is presented. The model is based on current concepts of metabolic control of tissue oxygen delivery and incorporates recent data from the literature regarding the influence of oxygen availability-to-demand ratio on intestinal vascular resistance and perfused capillary density. The model was used to evaluate the relative importance of resistance and exchange vessels in preventing cellular hypoxia during reductions in oxygen delivery or increments in oxygen demand. The model predicted that capillary recruitment is of greater quantitative significance than blood flow autoregulation in preventing cellular hypoxia when intestinal perfusion pressure is reduced. However, the combination of capillary recruitment and blood flow autoregulation provides a large margin of safety against tissue hypoxia in the intestine. Simulation results also predict that oxygen extraction plays a greater role than blood flow in providing additional oxygen to the hypermetabolic intestine irrespective of which control system (resistance or exchange vessel) is operating.
Role of tight-junctional pathways in bile salt-induced increases in colonic permeability
Authors: Freel R. W. , Hatch M. , Earnest D. L. , Goldner A. M.
Published: December 2017

The effects of a dihydroxy bile salt, taurochenodeoxycholate (TCDC), on the permeability and conductance of isolated, short-circuited segments of the rabbit descending colon were examined using conventional Ussing chamber techniques. Increasing concentrations of TCDC (1℃4 mM) produced dose-dependent increases in sodium backflux (JNas leads to m) and tissue conductance (Gt) when applied to either the mucosal or serosal salines. However, mucosal addition was twice as potent in increasing JNas leads to m and Gt at 4 mM. Tracer experiments indicated that the transepithelial serosal-to-mucosal fluxes of sodium and mannitol are via an aqueous, unrestricted, free-solution pathway, while albumin movements are restricted through this pathway both in the absence and presence of mucosal TCDC. The changes in JNas leads to m, JMans leads to m, and Gt caused by 4 mM mucosal TCDC were largely reversed by rinsing the mucosal chamber with fresh buffer. It was also observed that osmotically induced volume flows in the serosal-to-mucosal direction could offset or reverse the changes in Gt produced by 2 mM mucosal TCDC, suggesting that the enhanced conductance pathway is in series with the lateral intercellular spaces. Taken together, these results suggest that low concentrations of TCDC alter the integrity of tight-junctional complexes between the epithelial cells of the rabbit colon.
Evidence for a direct action of acetylcholine on the gastric oxyntic cell of the amphibian
Authors: Ruiz M. C. , Michelangeli F.
Published: December 2017

The possibility of a direct action of acetylcholine (ACh) on the oxyntic cell not mediated by histamine release was studied in resting isolated gastric mucosae. H+ secretion and histamine release, and their relationship, were studied under ACh stimulation and other conditions. ACh released histamine from mucosal stores and stimulated H+ secretion. H2-receptor blocker cimetidine largely inhibited ACh-induced stimulation of H+ transport but not histamine release. Atropine inhibited the cholinergic response in both histamine release and H+ secretion. The dose-response curves to ACh showed nonparallel increases in H+ secretion and histamine release. When dose-response curves to exogenous and endogenous histamine (released by ACh) were compared, it was found that ACh increased Vmax for endogenous histamine. Comparison of the effects of ACh with other experimental conditions such as tetragastrin treatment, K+ depolarization, or Na+-free nutrient solution showed that the amount of histamine released by ACh was insufficient to explain the observed rates of secretion. Stimulation by ACh was faster, greater, and more transitory compared with that by histamine. In mucosae maximally stimulated by histamine, ACh induced a further increase in H+ secretion. In the presence of cimetidine, potentiation between ACh and dibutyryl cAMP or isobutyl-methylxanthine was found. The results are consistent with ACh having a dual action on oxyntic and histamine-releasing cells. The action of ACh on the oxyntic cell would potentiate the effect of released histamine. It is suggested that ACh and released histamine act on the oxyntic cell through different second messengers, resulting in the potentiated response.
Transferrin and iron uptake by rat hepatocytes in culture
Authors: Page M. A. , Baker E. , Morgan E. H.
Published: December 2017

Hepatic iron and transferrin metabolism was studied using rat transferrin doubly labeled with 59Fe and 125I and adult rat hepatocytes in primary monolayer culture. Iron uptake was linear for 48 h while transferrin uptake was biphasic. Total transferrin and iron uptake increased in a linear manner as the transferrin concentration was raised up to at least 130 microM. This indicates that transferrin and iron are taken up primarily by nonspecific processes, possibly by endocytosis (absorptive or fluid) and by the action of iron chelators. However, some evidence indicated the presence of receptors for diferric transferrin on hepatocytes: the molar ratio of iron to transferrin accumulation increased with incubation time, transferrin and iron uptake was proportional to the iron saturation of the transferrin, apotransferrin displaced bound apotransferrin but had no effect on the binding of diferric transferrin, and the molar ratio of iron to transferrin uptake decreased with increasing transferrin concentrations.
A rat model for studying the intestinal circulation
Authors: Anzueto L. , Benoit J. N. , Granger D. N.
Published: December 2017

A preparation is described that allows for whole-organ studies on the rat intestinal microcirculation. The preparation is an in situ autoperfused segment of small intestine. An arterial perfusion circuit is established between the carotid and superior mesenteric arteries and a venous circuit between the superior mesenteric and jugular veins. This model allows for measurements of superior mesenteric arterial and venous pressures, blood flow, arteriovenous oxygen difference, lymph flow, capillary pressure, capillary reflection coefficient, and the capillary filtration coefficient. Preliminary studies using this model indicate a resting blood flow of approximately 120 ml X min-1 X 100 g-1. Resting intestinal oxygen consumption is approximately two to three times the value reported for dogs and cats. Experiments were performed to assess the responses of the preparation to commonly employed physiological perturbations, including pressure-flow autoregulation, functional hyperemia, and response to venous pressure elevations. The observed responses are consistent with intrinsic control of resistance and exchange vessels. The model should prove useful for future studies regarding the physiology and pathology of intestinal hemodynamics, oxygenation, and capillary fluid exchange.
Proglumide inhibition of trophic action of pentagastrin
Authors: Johnson L. R. , Guthrie P. D.
Published: December 2017

Proglumide, a glutaramic acid derivative, inhibits the acid secretory effects of gastrin and is said to be a specific gastrin receptor blocking agent. In the current study we have shown that proglumide inhibits the binding of gastrin to its receptor in rat oxyntic gland mucosa and tested whether this receptor is also responsible for the trophic effect of gastrin. In the first study 400 mg/kg proglumide injected with 250 micrograms/kg pentagastrin every 8 h for 48 h totally prevented the trophic effects of pentagastrin in rat oxyntic gland mucosa. Parameters measured included DNA synthesis and DNA, RNA, and protein content. In a second study the lowest maximally effective dose of proglumide was determined to be 100 mg/kg. The trophic effect of pentagastrin was inhibited in duodenal mucosa, colonic mucosa, and pancreas as well as oxyntic gland mucosa. These data demonstrate that proglumide blocks the trophic action of exogenous gastrin and suggest that the trophic effect of gastrin is mediated by the gastrin receptor.
Albumin influences sulfobromophthalein transport by hepatocytes of each acinar zone
Authors: Gumucio D. L. , Gumucio J. J. , Wilson J. A. , Cutter C. , Krauss M. , Caldwell R. , Chen E.
Published: December 2017

To determine whether profiles of decreasing concentration were generated among hepatocytes of the liver acinus during the transport of sulfobromophthalein sodium (BSP), rat livers were perfused with various concentrations of this dye (10 microM to 1 mM) in the presence and absence of albumin. After steady-state conditions for the biliary secretion of BSP had been attained, pieces of liver were rapidly frozen. Following the alkalinization of cryostat-cut sections, the relative concentration of BSP in hepatocytes of each zone and the effect of albumin on this localization were quantitated by microspectrophotometry. The results showed that BSP, perfused in the absence of albumin, was efficiently extracted by the liver (95% on a single pass), generating distinct profiles of decreasing cellular concentration from zone 1 to zone 3 at every concentration of BSP. However, the addition of albumin to the perfusate greatly reduced the extraction of BSP from the sinusoidal compartment and resulted in the abolition of the differences in BSP content between hepatocytes of zone 1 and zone 3. These results represent a direct demonstration that, as predicted by mathematical modeling, binding of BSP to albumin indeed results in a more homogeneous distribution of BSP within the liver acinus. A simple and direct microspectrophotometric method is therefore available to follow the changes in the relative concentration of BSP among the hepatocytes of the various acinar zones.
Insulinlike growth factors bind to specific receptors in isolated pancreatic acini
Authors: Williams J. A. , Bailey A. , Humbel R. , Goldfine I. D.
Published: December 2017

Recently we have demonstrated the existence of specific receptors for insulin on pancreatic acini. Employing 125I-labeled insulinlike growth factors (IGFs) and insulin, we report the existence of distinct receptors for IGF-I and IGF-II on mouse pancreatic acini. Insulin competes with 125I-IGF-I with 1,000-fold less potency. By contrast, insulin increases the binding of 125I-IGF-II to its receptor. IGF in turn inhibits 125I-insulin binding to its receptor but with 250-fold less potency. Thus, distinct receptors exist on acini for IGF-I, IGF-II, and insulin. Moreover, IGF, like insulin, stimulates sugar transport by acini. The mechanism of IGF stimulation may be similar to insulin, as the effect of maximal concentrations of the two peptides when added together is not additive. These results raise the possibility, therefore, that IGFs may be a new class of physiological regulators of pancreatic acinar cell function.
Development of nutrient transport systems in chick jejunum
Authors: Shehata A. T. , Lerner J. , Miller D. S.
Published: December 2017

Glutamate, beta-alanine, choline, and myoinositol transport was characterized in jejunal slices and brush-border membrane vesicles from 2- and 21-day chicks. Carrier-mediated, i.e., competitor-inhibitable, transport in slices (wet weight basis) and vesicles (protein basis) declined with age for the two amino acids but increased with age for myo-inositol; transport of choline did not change. These findings, along with previous data for the hexose system, cannot be explained solely by nonspecific changes in brush-border membrane architecture or permeability or by changes in the electrochemical sodium gradient that drives cotransport. They indicate that each specific brush-border membrane transport mechanism follows separate developmental time tables.
Determination of short-circuit current in the in vivo perfused rat colon
Authors: Knauf H. , Haag K. , Lubcke R. , Berger E. , Gerok W.
Published: December 2017

Current pulses (I) were injected into the lumen of proximal colonic segments in vivo, and the corresponding voltage deflections (delta PD) superimposed on the transcolonic PD were recorded. From the exponential decay of delta PD along the colon axis, the electrical length constant (lambda) was determined. Based on cable analysis the input resistance (= delta PD x = 0/I) and lambda made it possible to calculate the specific resistance (Rm) of the colonic epithelium as 128 +/- 16 omega X cm2. As Rm proved to be an ohmic resistor, the extrapolation from open-circuit PD (8-12 mV, lumen negative) to zero PD was feasible and made the calculation of short-circuit current (= PD/Rm) equal to 70 +/- 16 microA/cm2. In the presence of amiloride short-circuit current decreased to about 50%, whereas with theophylline it increased by about 30%. Substitution of luminal Na+ with choline or Cl- with cyclamate was associated with a marked increase of Rm. The rheogenic component of net Na+ transport was estimated to be only 8%. Electroneutral Na+ absorption functionally coupled with Cl- absorption displayed the characteristic feature of ion transport in the rat proximal colon.
Interaction between stimulants of exocrine pancreatic secretion in dogs
Authors: Beglinger C. , Grossman M. I. , Solomon T. E.
Published: December 2017

We measured bicarbonate and protein secretory responses to graded doses of intravenous caerulein and bethanechol and intraduodenal L-phenylalanine alone or with background secretin; graded doses of secretin alone or with background caerulein or L-phenylalanine; and background secretin plus graded doses of caerulein or L-phenylalanine plus background atropine sulfate. Potentiation (more-than-additive response) occurred for bicarbonate secretion between secretin and caerulein, between secretin and L-phenylalanine, but not between secretin and bethanechol. The only potentiating interaction for protein secretion was between secretin and low doses of caerulein. Atropine abolished the potentiated bicarbonate response to secretin plus L-phenylalanine but had no effect on the response to secretin plus caerulein. Potentiation between secretin and cholinergic mechanisms and cholecystokinin for pancreatic bicarbonate secretion may be an important regulatory mechanism, while potentiation of protein secretion with these stimulants does not appear to be important in dogs. A cholinergic mechanism mediates much of the bicarbonate potentiation between secretin and intestinal L-phenylalanine.
Effect of pH on phosphate transport into intestinal brush-border membrane vesicles
Authors: Danisi G. , Murer H. , Straub R. W.
Published: December 2017

The effect of pH on the rate of phosphate (Pi) uptake was studied in rabbit duodenal brush-border membrane vesicles. Pi uptake was found to be sodium dependent at all pH values tested (5.7-8.1). Further, the rate of Pi uptake depended on pH; for instance, with 100 mM external sodium, reducing the pH from 8.1 to 6.8 or 5.7 doubled the rate of Pi influx. At 100 mM external sodium, experiments under initial rate conditions, carried out with varying Pi concentrations and at pH values of 6, 6.8, or 7.6, showed that sodium-dependent Pi uptake was saturable at the three pH values tested; the apparent Km expressed in function of total Pi was not dependent on pH. Vmax was not affected between pH 6 and 6.8 but was significantly reduced at pH 7.6. Lowering external sodium lowered Vmax at all pH values investigated. At acid and alkaline pH the rate of Pi uptake was a sigmoidal function of the external sodium concentration. Hill coefficients, calculated from these experiments, exceeded unity and were unaffected by pH. At saturating sodium concentrations, the rate of Pi uptake was higher at pH 6 than at pH 7.6. The [Na]0.5 was lower at pH 7.6 than at pH 6. Further, sodium-dependent Pi uptake appeared to be electrogenic at acid and alkaline pH. It is concluded that the pH dependence of intestinal Pi transport is not an expression of preferential transport of monovalent or divalent phosphate. The pH dependence appears to reflect properties of the sodium-phosphate cotransport mechanism and is in part related to changes in the affinity of the transport system for sodium.
Effect of chloroquine on low-density lipoprotein catabolic pathway in rat hepatocytes
Authors: Hornick C. A. , Jones A. L. , Renaud G. , Hradek G. , Havel R. J.
Published: December 2017

Injection of 125I-low-density lipoprotein (LDL) into estradiol-treated rats substantially increases the volume of the multivesicular body compartment in hepatocytes. When these animals were additionally given chloroquine 60 and 120 min before injection of 125I-LDL, the amount of 125I retained by the liver increased threefold and the amount of label in multivesicular bodies increased fivefold, as determined by quantitative analysis of autoradiograms. Lamellar inclusions that appeared after chloroquine also contained a substantial fraction of 125I, whereas the fraction of 125I in secondary lysosomes was reduced. From these data it is concluded that the multivesicular bodies comprise an intermediate endocytic compartment, the conversion of which to secondary lysosomes is impeded by chloroquine.
Somatostatin metabolism: differences in clearance of N-terminal and central portions of molecule during perfusion of rat liver
Authors: Sacks H. S. , Terry L. C. , Wright R. K. , Stentz F. B.
Published: December 2017

Clearance of cyclic somatostatin (SRIF) from a plasma-free recirculating medium containing human erythrocytes and a bovine albumin fraction was measured with site-specific N-terminal (sheep B) and central core-directed (R101) radioimmunoassays during perfusion of the isolated rat liver (3-4 g). With the N-terminal radioimmunoassay (RIA), the t 1/2, hepatic clearance, and extraction of somatostatinlike immunoreactivity (SLI) were 20.9 +/- 2.0 (SE) min, 2.82 +/- 0.27 ml/min, and 35.2 +/- 3.4%. Corresponding values for the centrally directed assay were 51.0 +/- 6.3 min, 1.16 +/- 0.14 ml/min, and 14.4 +/- 1.8%. Clearances of immunoprecipitable 125I-Tyr-SRIF and [125I-Tyr11]SRIF were 6.56 and 1.06 ml/min, respectively, and were not saturable by 1 microM Tyr-SRIF and SRIF, respectively. SRIF (1.26 +/- 0.09 nM) and SRIF-28 (1.34 +/- 0.14 nM) clearances determined by R101 RIA were similar. After SRIF-28 perfusion, high-performance liquid chromatographic analysis of SLI showed 86% to be retained with the SRIF-28 peak and 14% with the SRIF peak, suggesting no major conversion of SRIF-28 to SRIF. Des-(Ala1,Gly2)-N3-Ac-SRIF and dihydrosomatostatin were cleared more rapidly than SRIF. Clearance of SLI by the perfusate without the liver was 12-43% of liver clearance, depending on the peptide examined. These results support the hypothesis that aminopeptidase and endopeptidase activities are involved in SRIF clearance by the intact liver. The activities appear to function independently. The intrachain disulfide bond of SRIF may confer relative stability during its hepatic metabolism.
Pancreatic polypeptide inhibits exocrine pancreatic responses to six stimulants
Authors: Beglinger C. , Taylor I. L. , Grossman M. I. , Solomon T. E.
Published: December 2017

We determined the effects of three different doses of pancreatic polypeptide (50, 200, and 800 pmol X kg-1 X h-1) on pancreatic responses to graded doses of intravenous secretin, caerulein, and bethanechol and intraduodenal HCl, L-phenylalanine, and sodium oleate in dogs. The two lowest doses of pancreatic polypeptide (PP), which produced blood levels lower than measured after a meal, significantly inhibited the pancreatic responses to secretin, caerulein, HCl, and L-phenylalanine; the highest dose of PP inhibited the responses to bethanechol and sodium oleate. There was no difference in the degree of inhibition of bicarbonate or protein secretion caused by pancreatic polypeptide. With secretin, caerulein, bethanechol, and sodium oleate, inhibition was most pronounced against lower doses and was surmountable with higher doses of these stimulants. Inhibition of responses to HCl and L-phenylalanine was observed at all doses of these stimulants. Inhibition of the exocrine pancreatic secretory responses to six different stimulants by PP suggests that this hormone may play an important role in regulation of postprandial pancreatic secretion.
Derivatives of CCK-(26-32) as cholecystokinin receptor antagonists in guinea pig pancreatic acini
Authors: Gardner J. D. , Knight M. , Sutliff V. E. , Tamminga C. A. , Jensen R. T.
Published: December 2017

In the present study we synthesized cholecystokinin-(26-32)-amide [CCK-(26-32)-NH2], N-acetyl-cholecystokinin-(26-32) [Ac-CCK-(26-32)], and N-acetyl-cholecystokinin-(26-32)-amide [Ac-CCK-(26-32)-NH2]. None of these peptides altered amylase secretion from dispersed acini prepared from guinea pig pancreas, but each peptide inhibited the stimulation of amylase secretion caused by the C-terminal octapeptide of cholecystokinin [CCK-(26-33)]. Half-maximal inhibition of CCK-(26-33)-stimulated amylase secretion occurred with 10 microM CCK-(26-32)-NH2, with 25 microM Ac-CCK-(26-32)-NH2, and with 100 microM Ac-CCK-(26-32). Ac-CCK-(26-32) caused a parallel rightward shift in the dose-response curve for CCK-(26-33)-stimulated amylase secretion. Ac-CCK-(26-32)-NH2 inhibited the stimulation of amylase secretion caused by CCK-(26-33), caerulein, or gastrin-(2-17) but did not alter the stimulation caused by carbachol, bombesin, physalaemin, A23187, vasoactive intestinal peptide, secretin, or 8-bromoadenosine 3',5'-cyclic monophosphate. There was a close correlation between the abilities of derivatives of CCK-(26-32) to inhibit binding of 125I-cholecystokinin (125I-CCK) to pancreatic acini and their abilities to inhibit the stimulation of amylase secretion caused by CCK-(26-33). Half-maximal inhibition of binding of 125I-CCK occurred with 5 microM CCK-(26-32)-NH2, with 7 microM Ac-CCK-(26-32)-NH2, and with 70 microM Ac-CCK-(26-32). These findings indicate that each of the three derivatives of CCK-(26-32) is a specific competitive antagonist of the interaction of cholecystokinin with its cell surface receptors on pancreatic acini.(ABSTRACT TRUNCATED AT 250 WORDS)
Radioreceptor and biological characterization of cholecystokinin and gastrin in the chicken
Authors: Vigna S. R.
Published: December 2017

Radioimmunoassay, radioreceptor assays, and bioassays were used to demonstrate that chicken brain and antrum extracts contain cholecystokinin (CCK)-like and gastrinlike peptides, respectively. C-terminal-specific radioimmunoassay of partially purified chicken CCK and gastrin gave dilution curves parallel to those of the mammalian peptides. Mouse cerebral cortical and rat pancreatic membrane radioreceptor assays were used to differentiate CCK- from gastrinlike peptides on the basis of the different CCK versus gastrin specificities of the two receptors. Confirmation of the biological activity of chicken brain CCK was obtained by stimulation of amylase secretion from rat pancreatic lobules in vitro. The specificity of this response was demonstrated by the inhibition of chicken CCK-stimulated amylase secretion by the specific CCK receptor antagonist dibutyryl cGMP. Chicken antral gastrin stimulated gastric acid secretion from the rat stomach in vivo. In contrast to previous hypotheses, it is proposed that chickens have significant amounts of an antral gastrinlike peptide and that therefore it is possible that gastrin is involved in the physiological regulation of gastric acid secretion in chickens.
Mechanisms of folate homeostasis
Authors: Steinberg S. E.
Published: December 2017

Recent work has provided information that allows the delineation of the mechanisms by which folate homeostasis is maintained. Dietary folates are converted to monoglutamates in the gut, absorbed by an active process, and distributed to tissues by the enterohepatic cycle, possibly utilizing folic acid binding proteins. During short periods of dietary deprivation, supply is maintained in the monoglutamate pools in the enterohepatic cycle as well as within cells. A net increase in available folate results from a decrease in tissue uptake and in subsequent polyglutamate synthesis, coupled with a fixed rate of conversion of polyglutamate to monoglutamate and release from the cell. The liver exerts substantial regulatory effect because of its mass, relatively rapid folate turnover, and the large folate flux through the enterohepatic cycle. In addition, there is a substantial, if more long-term, contribution from tissues that die and release folates (e.g., red blood cells), and a pathway exists that is capable of salvaging this folate and returning it to the liver for subsequent redistribution to actively proliferating cells.
Chronic electrical activity of cat intestine
Authors: Bortoff A. , Sillin L. F. , Sterns A.
Published: December 2017

Spontaneous electrical activity was recorded with bipolar electrodes from the gastrointestinal tracts of unanesthetized fasted cats (upper and lower cut-off frequencies: 35 and 3 Hz). In addition to slow waves (SWs) and spike potentials (SPs), the following three patterns of activity were recorded that are not observed in vitro. 1) Intense bursts of SPs (migrating spike complexes, MSCs) migrate caudally at a velocity of approximately 1 mm/s. MSCs resemble migrating myoelectric complexes (MMCs) in their velocity and by their traversal of intestinal anastomoses. SWs are usually suppressed during and immediately after the MSC, and, on their return, propagate at a higher velocity than they do prior to the MSC. Unlike its effect on MMCs, motilin does not appear to elicit MSCs, a finding consistent with the fact that MSCs occur infrequently in the duodenum and not at all in the antrum. 2) Bursts of SPs are found in the absence of recorded SWs. The SP bursts are of variable duration and occur virtually simultaneously at several recording sites, or propagate at 1-2 cm/s in either direction along the jejunum. The more usual caudally propagating SPs occur when SWs reappear. 3) "Minute rhythms," periods of spiking SWs, occur simultaneously over long lengths of upper bowel, sometimes including antrum, at intervals of about 1-2 min. It is proposed that, despite their differences, the cat MSC may be the functional counterpart of the MMC, that cat SWs are not omnipresent, and that the minute rhythms described here are of central origin.
Histamine action on guinea pig ileal mucosa
Authors: Cooke H. J. , Nemeth P. R. , Wood J. D.
Published: December 2017

Nerve-mediated and direct actions of histamine on mucosal transport function in the guinea pig ileum were investigated. Addition of histamine to the serosal side of flat sheet preparations in Ussing chambers evoked a transient increase in base-line short-circuit current that was due primarily to an increase in active chloride secretion. The mucosal response to histamine was mimicked by the H1-receptor agonist 2-methylhistamine, but not by the H2-receptor agonist dimaprit. The histamine-evoked response was prevented by the H1-receptor blocker pyrilamine, but not by the H2-receptor antagonist cimetidine. Thirty percent of the mucosal response to histamine was inhibited by tetrodotoxin. Intracellular electrical recording showed that histamine activated AH/type 2 myenteric neurons, and this response was abolished in the presence of pyrilamine. Local anesthetic action of pyrilamine was ruled out by direct electrical recording from myenteric neurons in the presence and absence of pyrilamine. Electrical field stimulation evoked a biphasic increase in short-circuit current. Histamine and 2-methylhistamine did not alter the sustained phase of the short-circuit current response to electrical field stimulation, although pyrilamine reduced the electrically evoked response by 22%. Muscarinic blockade with atropine reduced the stimulus-evoked response by 55%. When muscarinic receptors were blocked and electrical field stimulation applied, histamine increased the stimulus-evoked mucosal response by 22.3%. These results suggest that histamine increases short-circuit current and chloride secretion by acting at H1-receptor sites on both the enteric innervation of the mucosa and on the enterocytes.
Evidence for cardiac volume-receptor regulation of feline jejunal blood flow and fluid transport
Authors: Sjovall H. , Redfors S. , Biber B. , Martner J. , Winso O.
Published: December 2017

The aim of the study was to investigate the role of cardiac mechanoreceptors in the reflex regulation of intestinal blood flow and fluid transport. Feline cardiac mechanoreceptor activity was modified with two noninvasive techniques: positive-pressure ventilation (PPV) and inspiratory resistance breathing (IRB). A jejunal segment with intact vascular and nervous supply was isolated and exposed to cholera toxin as a model for intestinal secretion. The results revealed that PPV induced a pronounced intestinal vasoconstriction and a marked inhibition of choleraic secretion. IRB had the opposite effects. The responses were well correlated with changes in central blood volume and either markedly reduced or abolished by vagotomy, intestinal alpha-adrenoreceptor blockade, or postganglionic mesenteric denervation. The results indicate that cardiac mechanoreceptors with vagal afferents may mediate the observed reflex responses, and hence this receptor station may be of importance in the normal reflex control of intestinal hemodynamics and fluid transport.
Cholecystokinin receptor antagonists
Authors: Gardner J. D. , Jensen R. T.
Published: December 2017

Since 1979 three classes of cholecystokinin receptor antagonists have been described: 1) derivatives of cyclic nucleotides, 2) derivatives of amino acids, and 3) C-terminal fragments or partial sequences of cholecystokinin. These various antagonists share a number of common features, such as their specific, reversible, and competitive actions, but they vary in the potency with which they inhibit the actions of cholecystokinin.
Ontogeny of gastric mucosal muscarinic receptor and sensitivity to carbachol
Authors: Seidel E. R. , Johnson L. R.
Published: December 2017

Development of the muscarinic cholinergic receptor and sensitivity of oxyntic gland mucosa to a muscarinic agonist were studied in rats of various ages. The gastric lumen of the fetal rat at the 20th day of gestation contained a statistically significant amount of basal pepsin, which increased log linearly over the first 30 days of life. Carbachol was effective in stimulating the secretion of pepsin as early as 12 h after birth. Basal acid could be measured in the gastric lumen 12 h after birth. The secretion of basal acid increased log linearly over the first 30 days of life. Carbachol was an effective secretagogue even in the fetal rat. The density of the muscarinic cholinergic receptor of the adult rat oxyntic gland mucosa was 99.3 fmol/mg protein with an apparent equilibrium dissociation constant for quinuclidinyl benzilate of 0.40 nM. The receptor was well developed even in the fetal rat, which bound 79.6 fmol/mg protein with an apparent equilibrium dissociation constant of 0.26 nM. Except for immediately after birth, receptor density was maintained between 70 and 90% of the adult level over the first 30 days of life. These results suggest that cholinergic regulation of gastric acid and pepsin secretion is probably functional by either late gestation or at least immediately after birth.
Effects of epidermal growth factor on gastrointestinal secretions
Authors: Konturek S. J. , Cieszkowski M. , Jaworek J. , Konturek J. , Brzozowski T. , Gregory H.
Published: December 2017

Epidermal growth factor (EGF) has been reported to stimulate epithelial cell proliferation and to inhibit gastric H+ secretion, but no details of the latter effect have been studied. This paper reports the effects of EGF on gastric and pancreatic secretions induced by various stimulants in vivo on conscious dogs and in vitro on isolated rabbit gastric glands. EGF was found to be an effective inhibitor of H+ secretion induced from the fully innervated and vagally denervated portions of the stomach stimulated by secretagogues activating receptors of the parietal cells (pentagastrin, histamine, and urecholine) and by natural stimulants such as sham or ordinary feeding. It appears to act directly on the parietal cells, as the inhibitory effect in vivo was not accompanied by any change in postprandial serum gastrin level. In addition, EGF was found to suppress H+ formation in the isolated gastric glands, both under resting conditions and after stimulation with histamine, carbachol, or dibutyryl cAMP. EGF failed to affect pancreatic response to exogenous hormones (secretin and cholecystokinin) but reduced postprandial secretion probably because of inhibition of H+ secretion from the subsequent reduction in duodenal acid loads. We conclude that EGF is a potent, specific, and direct inhibitor of H+ secretion from the parietal cells and that it does not affect alkaline gastroduodenal or pancreatic secretion.
Ion transport by rabbit descending colon: mechanisms of transepithelial potassium transport
Authors: McCabe R. D. , Smith P. L. , Sullivan L. P.
Published: December 2017

In vitro preparations of rabbit descending colon were studied under steady-state short-circuit conditions to determine 1) the K concentration dependence of unidirectional K fluxes; 2) the effects of the K channel blocker barium and the diuretic agent furosemide; and 3) the steady-state tissue specific activity of 42K when added to the luminal bathing solution. Results from these studies reveal that 1) labeling of cellular K from the mucosal solution is less than 25% of that from the serosal solution; 2) both unidirectional K fluxes are composed of saturable and nonsaturable components; 3) the serosal-to-mucosal saturable component is abolished by ouabain, and subsequent addition of 2,4-dinitrophenol abolishes the saturable component of the mucosal-to-serosal K flux; 4) luminal or serosal barium alters K transport in a manner consistent with the presence of barium-sensitive K conductances at both membranes; 5) luminal furosemide did not alter K transport; and 6) there is no shunt selectivity for K. We conclude that the majority of both unidirectional K fluxes follow a transcellular pathway and that both the apical and basolateral membranes possess active K uptake mechanisms and barium-sensitive K exit mechanisms.
Rabbit proximal colon: a distinct transport epithelium
Authors: Sellin J. H. , DeSoignie R.
Published: December 2017

Rabbit proximal colon (PC), examined in vitro, exhibits transport characteristics distinct from distal colon. Unlike distal colon, PC does not demonstrate amiloride-inhibitable electrogenic Na absorption. Additionally, neither amphotericin nor "stimulatory" anions induce Na absorption in PC. Electrical measurements and radioisotopic flux studies under short-circuit conditions indicate that PC is a moderately leaky epithelium with a conductance (9.0 +/- 0.2 mS) midway between ileum and distal colon; under basal conditions PC has Na and Cl transport rates near zero, and 5.5 microM epinephrine (Epi) stimulates electrically silent Na-Cl coupled absorption. The mechanism of this cotransport was investigated further: Cl substitution with either sulfate or gluconate did not substantially alter Epi-enhanced Na absorption. The Epi stimulation of Cl absorption in a Na-free solution was diminished. Amiloride, 10(-3) M, inhibited Epi-enhanced Na absorption by approximately 50%. The effects of cAMP-mediated (theophylline or 8-bromo-cAMP) and Ca-mediated (ionophore A23187) secretory stimuli were examined. In the basal state, none of these agents had a consistent effect on ion transport. However, after stimulation of Na and Cl absorption by Epi, both of the cAMP-related secretagogues had a marked antiabsorptive effect on Na and Cl transport. The antiabsorptive effects of Ca ionophore A23187 were less marked. These results suggest that rabbit proximal colon a) does not share the transport properties characteristic of distal colon, b) possesses an Epi-sensitive, Na-Cl-coupled absorptive pathway, and c) responds to secretory stimuli in an antiabsorptive manner rather than by electrogenic secretion.
Insulin and islet cell transplant--effect on intestinal uptake of lipids
Authors: Thomson A. B. , Rajotte R. V.
Published: December 2017

A previously validated in vitro technique was used to determine the effect of once-daily injections of NPH insulin (NPH) and islet cell transplant (ICT) on the enhanced uptake (Jd) of lipids into the intestine of diabetic rats. Three months after ICT, the urine volume, urine glucose, and fasting blood sugars were near normal. The Jd of lauryl alcohol was used to measure the effective resistance of the unstirred water layer (UWL); NPH was associated with an increase in UWL in the jejunum when the bulk phase was stirred or unstirred and a rise in UWL in the ileum when the bulk phase was unstirred but had no effect on UWL in the colon. The Jd of a homologous series of saturated medium-chain-length fatty acids in untreated diabetic rats was reduced with NPH and ICT. The Jd of cholesterol was lower in diabetic rats treated with NPH or ICT than in untreated diabetic rats over a wide range of concentrations of cholesterol, bile acid, and bile acid/cholesterol. The colon was less permeable than the jejunum to fatty acids or fatty alcohols. In contrast to the small intestine, diabetes had no effect on colonic uptake of these probes. Thus, injection of exogenous insulin or endogenous insulin supplied by ICT in diabetic rats reduced the Jd of lipids, normalized the effective resistance of the UWL, and reduced the enhanced passive permeability of the jejunum observed in diabetic animals.
Polyamines in the response to intestinal obstruction
Authors: Seidel E. R. , Haddox M. K. , Johnson L. R.
Published: December 2017

The gastrointestinal mucosa immediately proximal to an intestinal obstruction becomes hyperplastic. Since mucosa that is distal to an obstruction atrophies, it appears that the adaptational response to obstruction is regulated by local factors. The hypothesis tested in these studies is that increased polyamine metabolism in the gut proximal to an obstruction is a required local event in the hyperplastic process. Ligation of either rat ileum or colon resulted within 66 h in a doubling of total RNA, DNA, and protein content in the 2 cm of mucosa immediately proximal to the tie. The trophic response was accompanied by an increase in primary amine content of the intestinal chyme in the segment of gut under investigation. These amines were not removed from intestinal chyme by 24 h of lyophilization, suggesting that the more volatile short-carbon-chain aliphatic amines were of limited importance. Subsequent studies focused on polyamine metabolism. Ornithine decarboxylase (ODC) activity was increased in the mucosa proximal to obstruction. In the ileum, ODC activity was increased 10-fold over control values and in the colon about 2-fold. Increased ODC activity was accompanied by corresponding increases in mucosal polyamine content. Finally, treatment of rats with difluoromethylornithine, a selective, irreversible inhibitor of ODC, partially prevented the trophic response to intestinal obstruction.
Catabolism of neurotensin in interstitial fluid of the rat stomach
Authors: Bunnett N. W. , Mogard M. , Orloff M. S. , Corbet H. J. , Reeve J. R. , Walsh J. H.
Published: December 2017

The catabolism of neurotensin (NT) was studied in the gastric submucosa of the conscious rat using a novel technique to obtain a dialysate of interstitial fluid. A microdialysis fiber system was surgically implanted into the gastric submucosa, and 2 days later experiments were commenced on conscious animals. Isotope-labeled NT was administered to the tissue, and a dialysate of the submucosal interstitial fluid was collected. In the dialysate, NT and catabolites of NT formed in the interstitial fluid were identified and quantitated by high-pressure liquid chromatography. The catabolism of 125I-NT-(1-13) and [3H]NT-(1-13) was studied as was the further breakdown of the major catabolites. NT-(1-13) was, regardless of the type of label, catabolized mainly into NT-(1-8), NT-(9-13), NT-(1-11), and free tyrosine. None of the catabolites formed is known to possess significant biological activity. NT-(9-13) was rapidly cleared, whereas the amino-terminal fragments NT-(1-8) and NT-(1-11) were more resistant to degradation. The biological half-life of neurotensin in the gastric submucosa of the rat was between 9 and 15 min.
On the mechanism of luminal CO2 generation during jejunal bicarbonate absorption
Authors: Feldman G. M. , Arnold M. A. , Charney A. N.
Published: December 2017

The mechanism of the increase in luminal CO2 tension (PCO2) that accompanies jejunal HCO-3 absorption is unknown. One possibility is that mucosal metabolism and the reaction of absorbed HCO-3 with blood buffers in mucosal capillaries govern luminal PCO2. To evaluate this possibility, jejunal segments of anesthetized adult male Sprague-Dawley rats were perfused in vivo with modified Ringer solutions with varying PCO2 levels (0-141 mmHg). Arterial PCO2 was varied by mechanical ventilation (20-70 mmHg). The net flux of CO2 gas into bulk luminal fluid varied directly with the transmucosal PCO2 gradient both in the absence (r = 0.98, P less than 0.001) and presence of net HCO-3 absorption (r = 0.97, P less than 0.001). The apparent permeability coefficient for CO2 gas across the jejunal mucosa was relatively low (2 X 10(-4) cm3 X s-1 X cm length -1) and was not affected by net HCO-3 absorption. Under conditions of equal arterial blood and perfusate PCO2 levels (40 mmHg), the PCO2 in mucosa and effluent was 51 and 44 mmHg, respectively, in the absence and 62 and 48 mmHg, respectively, in the presence of net HCO-3 absorption. These results suggest that CO2 diffuses from the mucosal region into bulk liminal fluid during net HCO-3 absorption in the rat jejunum. In addition, we found in vitro that the elevation of mucosal PCO2 above arterial PCO2 during net HCO-3 absorption can be quantitatively accounted for by metabolism and the admixture of absorbed HCO-3 with blood buffers.