bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of cholecystokinin-octapeptide on gastric motility of anesthetized dogs
Authors: Kuwahara A. , Ozawa K. , Yanaihara N.
Published: December 2017

The present experiments examined the local effects of cholecystokinin-octapeptide (CCK-8) and related peptides on gastric motility of anesthetized dogs. Peptides were injected through the gastroepiploic artery at doses of 1.0, 2.5, 5.0, 10.0, and 20.0 ng/ml. CCK-8 and its analogues (Glt-CCK-8, pGlu-CCK-8, and Suc1-MePhe8-CCK-7) increased gastric smooth muscle contraction in a dose-dependent manner. ED50 of CCK-8 was 2.97 +/- 0.63 ng/ml. Administration of atropine (100–200 micrograms/kg) inhibited the effects of both CCK-8 and pentagastrin; however, hexamethonium (5 mg/kg) failed to block the contractile response induced by CCK-8 and pentagastrin. These results indicate that CCK-8 and related peptides can act as local modulators in controlling the neural regulation of gastric motility.
Swallow-evoked peristalsis in opossum esophagus: role of cholinergic mechanisms
Authors: Gidda J. S. , Buyniski J. P.
Published: December 2017

This study examined the role of cholinergic mechanisms in esophageal smooth muscle of anesthetized opossums. Swallow-induced motility was recorded manometrically before and after treatment with physostigmine or metoclopramide. At the 5-cm site above lower esophageal sphincter (LES) the latency, duration, and amplitude of swallow-evoked contractions were 2.1 +/- 0.12 (SE) s, 1.8 +/- 0.31 s, and 74.5 +/- 6.1 mmHg, respectively. At the 1-cm site the respective values were 4.6 +/- 0.38 s, 3.8 +/- 0.24 s, and 42.0 +/- 4.6 mmHg. The calculated speed of peristalsis was 1.72 +/- 0.21 cm/s. After intravenous treatment with the physostigmine (100 micrograms X kg-1 X h-1), each swallow produced contractions that were simultaneous, repetitive, and of long duration. The values of duration and amplitude of contraction at the 5- and 1-cm site after physostigmine treatment were significantly higher than controls (P less than 0.01). There was a significant decrease in the latency of contraction at all sites. This resulted in a significant faster speed of peristalsis. Atropine (30 micrograms/kg iv) reversed the influence of physostigmine, resulting in a significantly slower speed of peristalsis. Metoclopramide (10 mg/kg iv) resulted in several changes in swallow-evoked contractions similar to those observed after physostigmine treatment. These data suggest that alteration in cholinergic mechanisms results in disordered esophageal peristalsis in the opossum.
Physiological characteristics of ovine pyloric sphincter
Authors: Ruckebusch Y. , Malbert C. H.
Published: December 2017

A special probe was validated to record in situ pyloric sphincter activity by changes in fiber-optic light transmission and sleeve pressure associated with the propagation of antroduodenal contractions, the onset of the phase of regular spiking activity (RSA) of the migrating myoelectric complex, the RSA-like events elicited by duodenal acidification, and the pharmacological stimulation of the gastroduodenal junction. Rapid changes in light transmission associated with antroduodenal contractions were super-imposed on slow variations, suggesting the existence of both phasic and tonic components in pyloric sphincter activity. The phasic activity coincided with isolated closures of the pyloric orifice, closures associated with antral or duodenal bulb contractions, and with long-lasting rhythmic closures during the development of the RSA phase. The resting tone increased during antral and/or duodenal stimulation and by feeding “appetizers” but decreased during antroduodenal quiescence and at the onset of general anesthesia. It is concluded that the ovine pylorus predominantly exists in a state of low resting tone but can act as a true sphincter with both inherent tonic and phasic activity.
Gastrointestinal myoelectric correlates of vomiting in the dog
Authors: Lang I. M. , Marvig J. , Sarna S. K. , Condon R. E.
Published: December 2017

Prior to vomiting, two gastrointestinal contractile events occur in succession: a giant contraction that propagates retrograde from mid-small intestine to the antrum (RGC) and a series of phasic contractions that occur at all levels of the gastrointestinal tract. We quantitatively examined the gastrointestinal myoelectric events associated with vomiting and correlated them with the previously defined contractile events. Twelve dogs of either sex were implanted with electrical or contractile recording devices implanted on the stomach and small intestine. After an overnight fast, gut activity was recorded before and after apomorphine administration (2.5–15 micrograms/kg, iv). We found that the RGC was correlated with two successive electrical events: disruption of electrical control activity (ECA) cycling and a potential change occurring at the upstroke of the RGC. However, the initial myoelectric event associated with vomiting was ECA frequency slowing of the antrum and lower half of the small intestine. The post-RGC phasic contractions were associated with ECA-dependent response activity and occurred during the period of ECA frequency slowing. Atropine (100 micrograms/kg iv) blocked the RGC and its associated electrical events but not the slowing of ECA frequency. Supradiaphragmatic vagotomy eliminated all gastrointestinal contractile and myoelectric events but antral ECA frequency slowing. Spontaneous occurrences of the myoelectric correlates of vomiting were not different from those activated by apomorphine. These results suggest that ECA disruption may be important for retrograde propagation of the RGC. The function of ECA frequency slowing, however, remains unknown.
Dose-response effects of atropine on pancreatic secretory response to intestinal tryptophan in dogs
Authors: Vazquez-Echarri J. , Baumgartner D. , Singer M. V.
Published: December 2017

In dogs with gastric and pancreatic fistulas, we studied the effect of intravenous infusion of atropine in doses of 0.9, 1.8, 7, and 29 nmol X kg-1 X h-1 on the pancreatic secretory response to graded loads of intraduodenal infusions of tryptophan, given with a secretin background. Infusions of 1.8, 7, and 29, but not 0.9 nmol X kg-1 X h-1 of atropine sulfate significantly (P less than 0.05) decreased the incremental protein response to all loads of tryptophan. The cumulative incremental protein output was reduced by 44, 37, and 52%, respectively. Infusions of 1.8, 7, and 29 nmol X kg-1 X h-1 of atropine significantly decreased by approximately 50% the incremental bicarbonate response to low (0.12 and 0.37 mmol/h) but not high loads (1.1, 3.3, and 10 mmol/h) of tryptophan. The inhibitory potency of the effective doses of atropine did not differ significantly. Only the highest dose of atropine significantly increased heart rate by 76%. These findings indicate that 1) in the intact animal, the minimal dose of atropine required for inhibition of pancreatic bicarbonate and protein response to intraduodenal tryptophan seems to be 1.8 nmol X kg-1 X h-1, a dose that causes probably few systemic effects, since it does not increase heart rate; and 2) the inhibitory action of atropine on the pancreatic response to tryptophan appears to be an “all-or-none” effect
Ionic regulation of Na absorption in proximal colon: cation inhibition of electroneutral Na absorption
Authors: Sellin J. H. , De Soignie R.
Published: December 2017

Active Na absorption (JNanet) in rabbit proximal colon in vitro is paradoxically stimulated as [Na] in the bathing media is lowered with constant osmolarity. At 140 mM [Na]o, JNanet is -0.6 +/- 0.4 mueq X cm-2 X h-1, whereas at 50 mM [Na]o JNanet is 5.0 +/- 0.7 mueq X cm-2 X h-1, P less than 0.01. JNas----m is a linear function of [Na]o, suggesting a diffusional flux. JNam----s increases almost linearly from 0 to 50 mM [Na]o but then plateaus and actually decreases from 50 to 140 mM [Na]o, consistent with inhibition of an active transport process. Both lithium and Na are equally effective inhibitors of JNanet, whereas choline and mannitol do not block the high rate of JNanet observed in decreased [Na]o. Either gluconate or proprionate replacement of Cl inhibits JNanet. Removal of K or HCO3 does not alter Na absorption. JNanet at lowered [Na]o is electrically silent and is accompanied by increased Cl absorption; it is inhibited by 10(-3) M amiloride and 10(-3) M theophylline but not by 10(-4) M bumetanide. Epinephrine is equally effective at stimulating Na absorption at 50 and 140 mM [Na]; yohimbine does not inhibit JNanet at 50 mM [Na]o. Na gradient experiments are consistent with a predominantly serosal effect of the decreased [Na]o. These results suggest that Na absorption in rabbit proximal colon in vitro is stimulated by decreased [Na]; the effect is cation specific, both Na and Li blocking the stimulatory effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Na-H exchange regulates intracellular pH in isolated rat hepatocyte couplets
Authors: Henderson R. M. , Graf J. , Boyer J. L.
Published: December 2017

Intracellular pH (pHi) was measured directly in isolated rat hepatocyte couplets using pH sensitive microelectrodes. The hepatocytes were maintained in a minimal salt buffer without added hormones or serum. Values of pHi (6.99 +/- 0.12, mean +/- SE) were close to their Nernst equilibria. After intracellular acidification with ammonium chloride, pH regulation was inhibited with 1 mM amiloride or by omission of external sodium, consistent with a Na-H exchange mechanism. Mean intracellular buffering power, in the nominal absence of carbon dioxide, was 34.1 +/- 11.4 mM. In the presence of external bicarbonate, amiloride or omission of sodium slowed, but did not completely inhibit recovery from acidification, indicating that additional pHi regulation mechanisms may operate in this preparation. These studies provide a direct measurement of pHi in hepatocyte couplets and indicate that Na-H exchange, together with a bicarbonate dependent system are important mechanisms for pHi regulation in this preparation.
Modulation of hepatic biotransformation and biliary excretion of bile acid by age and sinusoidal bile acid load
Authors: Baumgartner U. , Miyai K. , Hardison W. G.
Published: December 2017

Pericentral hepatocytes excrete bile acids more slowly and biotransform them more than periportal cells. This may reflect adaptation to low pericentral bile acid concentration or may be intrinsic. We studied two models in which pericentral bile acid concentrations are high: the 72-h choledocho-caval shunt (CCS) rat and the 3- to 4-wk-old rat. Livers were perfused forward or backward to assess periportal or pericentral hepatocyte function. Taurodeoxycholate (TDC) was infused at 32 nmol X min-1 X g liver-1, and a bolus of [3H]TDC was given to assess metabolism and excretion of bile acids. In CCS livers perfused backward, pericentral cells resembled periportal cells of controls in that time to excrete 50% of administered [3H]TDC (t50) was reduced by two-thirds and [3H]TDC biotransformation was reduced by about half. In young livers t50 was half that of adult livers when perfused backward. Biotransformation, however, was not reduced. Young livers biotransformed more than adult controls for any given residence time of bile acid in the liver. We conclude that the difference between pericentral and periportal cells as regards bile acid processing is adaptive. Livers from young rats biotransform more bile acid than those from controls under similar conditions.
Vascular reactivity in experimental portal hypertension
Authors: Bomzon A. , Blendis L. M.
Published: December 2017

Portal hypertension (PHT) is known to be associated with a hyperdynamic circulation, yet the pathogenesis of both remains unclear. Therefore, we have studied serially the relationship between portal pressure and in vitro peripheral vascular responsiveness in an animal model of presinusoidal PHT. In rats with partial portal vein stenosis (PPVS) or sham-operated (SO) controls, we studied contractile responses to cumulative doses of norepinephrine (NE) and to a single dose of 0.8 microM NE of 20-mm helically cut strips of thoracic aorta. At both 2 and 10 days postoperatively, the portal pressures (mean intrasplenic pressure) in PPVS, 14.3 +/- 1.5 mmHg and 14.1 +/- 1.3 mmHg were significantly elevated compared with SO controls, 7.6 +/- 0.6 mmHg (P less than 0.005) and 9.7 +/- 0.5 mmHg (P less than 0.01), respectively. Yet, there was no significant differences between the two groups in the Rmax and ED50 of the contractile response curves to cumulative doses of NE as well as in the fast (phase 1) and slow phase (phase 2) of the contraction to 0.8 microM NE. In contrast, at 21 days, portal pressure in the PPVS rats fell to 11.0 +/- 0.7 mmHg but remained significantly higher than that of the SO controls, 8.2 +/- 1.0 mmHg (P less than 0.05). This occurred in conjunction with a significant decrease in Rmax [698 +/- 87 mg (PPVS) vs. 1148 +/- 92 mg (SO); P less than 0.005] but no significant change in ED50, indicating a decreased sensitivity to NE due to an alteration in alpha-adrenoreceptor function.(ABSTRACT TRUNCATED AT 250 WORDS)
VIP and PHI in the pig pancreas: coexistence, corelease, and cooperative effects
Authors: Holst J. J. , Fahrenkrug J. , Knuhtsen S. , Jensen S. L. , Nielsen O. V. , Lundberg J. M. , Hokfelt T.
Published: December 2017

The human vasoactive intestinal polypeptide (VIP) precursor contains a sequence, a peptide with an N-terminal histidine and C-terminal methionine (PHM), which is 93% homologous to the porcine intestinal peptide, (PHI) a peptide having N-terminal histidine and C-terminal isoleucine amide, suggesting that PHI could be a product of the porcine VIP precursor. If so, VIP-producing nerves would be expected to produce and release PHI in addition to VIP. We studied this in the pig pancreas. By immunohistochemistry, we identified nerve cell bodies in local ganglia and nerve fibers that were both PHI and VIP immunoreactive, innervating exocrine as well as endocrine structures. During electrical stimulation of the vagus nerve supply to the isolated perfused pig pancreas, a synchronous and approximately equimolar release of immunoreactive PHI and VIP was observed. Both responses were abolished by hexamethonium and could be copied by cholinergic agonists. Infusions of PHI and VIP at 10(-9) M stimulated the exocrine secretion of fluid and bicarbonate, and the effect of a combination of the two peptides was additive. In addition, both peptides stimulated insulin as well as glucagon secretion. By gel chromatography the VIP immunoreactivity in the venous effluent corresponded precisely to synthetic VIP, but only 24% of the PHI immunoreactivity corresponded to synthetic PHI; a larger peptide (mol wt 5,000-7,000) was responsible for the majority. The biological activity of this component is unknown. The results suggest that both VIP and PHI, released from intrapancreatic nerve fibers, participate in the parasympathetic control of pancreatic secretion.
Effect of central administration of motilin on migrating complexes in the dog
Authors: Hashmonai M. , Go V. L. , Yaksh T. , Szurszewski J. H.
Published: December 2017

The effects of intravenous, intrathecal, and intracerebroventricular injection of motilin on the interdigestive myoelectric (MMC) activity of the stomach and small intestine were examined in conscious dogs. To monitor electrical activity, electrodes were implanted on the stomach and small bowel. To inject motilin into the central nervous system, catheters were chronically positioned in the intrathecal space at the lumbar level and in one of the lateral cerebral ventricles. In all dogs, intravenous injection of motilin caused a transient increase in the plasma concentration of motilin and initiated gastric MMCs, which propagated aborally to the ileum. Intrathecal and intracerebroventricular injections of motilin did not affect plasma motilin levels and did not induce MMCs. These data suggest that initiation of MMCs after intravenous injections of motilin occurs through receptors for motilin possibly located outside the central nervous system. These data also suggest the hypothesis that initiation of naturally occurring MMCs in the dog may not be dependent on endogenous release of motilin from the central nervous system.
Mechanisms involved in ketone body release by rat liver cells: influence of pH and bicarbonate
Authors: Fafournoux P. , Demigne C. , Remesy C.
Published: December 2017

The aim of the present work is to study the intra- and extracellular concentration gradient of ketone bodies across the hepatic cell membrane, ketone bodies released by liver cells, and the effects of changes in acid-base status on these processes. Ketone bodies appeared to be released by liver cells against a concentration gradient both in vivo and in vitro (ratio intra- to extracellular, acetoacetate approximately 0.5, 3-hydroxybutyrate approximately 0.8). In vitro, a decrease in external pH and bicarbonate gradient was associated with a reduction of ketone body gradients and efflux rates. Analysis of the distribution ratio of ketone bodies as a function of delta pH across the cell membrane indicates that additional factors must be invoked to account for the observed distribution ratios. These data along with measurements of ketone body efflux are consistent with the existence of a system promoting the efflux of ketone bodies from liver cells, which is trans-stimulated by external bicarbonate. In vivo, ketogenesis was also inhibited by acidosis, and slightly enhanced by bicarbonate infusion, although this was not solely due to effects on transfer across the cell membrane. The study indicates that the hepatic release of ketone bodies might be auto-limited by ketoacidosis.
Effects of ethanol on gastric epithelial cell phospholipid dynamics and cellular function
Authors: Bailey R. E. , Levine R. A. , Nandi J. , Schwartzel E. H. , Beach D. H. , Borer P. N. , Levy G. C.
Published: December 2017

The lipid profile of isolated gastric superficial epithelial cells (SEC) was evaluated by proton nuclear magnetic resonance spectroscopy (1H-NMR). The most conspicuous resonance band in SEC spectra was due to the protons of +N(CH3)3 groups of phosphatidylcholine and, to a lesser degree, other phospholipid derivatives, on the basis of their chemical shift and addition of purified phospholipids. NMR of cell lysates and phospholipid extracts of SEC in deutero-chloroform provided further spectral resolution of these components. Phospholipase or ethanol treatments of SEC produced membrane disorganization reflected as increased peak intensity of the phospholipid signals. In addition, ethanol, in a dose-dependent manner, attenuated paranitrophenyl phosphatase activity, which correlated with inhibition of total and ouabain-sensitive 86Rubidium chloride uptake by SEC. This study suggests that NMR used in conjunction with other biochemical techniques can monitor SEC membrane structure-function relationships. NMR is a potentially powerful noninvasive probe to show changes in lipid membrane organization induced by low concentrations of ethanol (1%) and may indicate an early sign of "cytotoxicity" in intact SEC.
Rat hepatic bile acid sulfotransferase: enzyme response to androgens and estrogens
Authors: Collins R. H. , Lack L. , Killenberg P. G.
Published: December 2017

Rat liver bile sulfotransferase activity can be divided into a fraction that reacts with a monoclonal antibody (PK1B) and another fraction that does not. This work was performed to analyze the known response of hepatic bile acid sulfotransferase activity to androgens and estrogens by determining the effect of treatment on the proportion of bile acid sulfotransferase activity that possessed the epitope for PK1B monoclonal antibody. Activity in treated animals was further characterized by high-performance liquid chromatography (HPLC) analysis following purification by PK1B-immunoadsorption chromatography. The results indicate that estrogens and androgens affect the subset of enzyme activity that has the PK1B epitope more than the population that does not. HPLC demonstrates that increases and decreases in activity that follow treatment with androgens and estrogens are mirrored by the proportion of the PK1B-reactive protein that exhibits a relative molecular weight (Mr) greater than 170,000. Radial immunodiffusion assays of hepatic supernatant using a polyclonal antibody raised against PK1B-reactive bile acid sulfotransferase show that changes in specific activity that follow treatment are the result of changes in enzyme protein concentration.
Kinetic evidence for separate systems in transport of D- and L-methionine by rat small intestine
Authors: Brachet P. , Alvarado F. , Puigserver A.
Published: December 2017

The kinetics of D- and L-methionine uptake by rings of everted intestine in vitro are consistent with a saturable Michaelis-Menten component (Km = 11.7 and 1.7 mM; Vmax = 0.53 and 0.74 mumol X g-1 X min-1 for D- and L-methionine, respectively) plus a linear, diffusional one. All the data could be fit with a diffusion constant (Kd = 3.2 microliters X g-1 X min-1), which was essentially the same, independent of whether it was estimated by iteration or by using the extracellular marker, inulin. Similar results were obtained from in vivo perfusion experiments, except that the diffusional term was negligible. D-Methionine was found to inhibit L-methionine uptake by intestinal rings according to fully noncompetitive kinetics (Ki = 45 mM). Another set of experiments with jejunal brush-border membrane vesicles showed that D-methionine uptake is dependent on a Na+ gradient and is significantly inhibited by L-methionine and L-proline, but not by beta-alanine and alpha-methylaminoisobutyric acid. Our results indicate that, in rat jejunum, D-methionine is taken up through a Na+-dependent pathway distinct from the neutral amino acid (L-methionine) carrier and from the imino acid (L-proline, alpha-methylaminoisobutyric acid, beta-alanine) carrier.
Bile acid inhibition of taurocholate uptake by rat hepatocytes: role of OH groups
Authors: Bellentani S. , Hardison W. G. , Marchegiano P. , Zanasi G. , Manenti F.
Published: December 2017

To define further the structural specificity of the taurocholate uptake site, we studied the ability of a variety of taurine-conjugated bile acids with differing hydroxyl substituents on the sterol moiety to inhibit [14C]taurocholate uptake. Rat hepatocytes isolated by collagenase perfusion were incubated in a tris(hydroxymethyl)aminomethane-phosphate buffer containing [14C]taurocholate (2.5-100 microM) in the presence or absence of inhibitor bile acid. Stronger inhibitors were studied at a fixed concentration of 5 microM, weaker ones at 25 microM. Initial uptake velocity was measured by sedimenting an aliquot of cells through silicone oil into 3 N KOH every 15 s for 1 min. Uptake velocity (nmol X mg protein-1 X min-1) could then be related to taurocholate concentration and a Vmax and Km could be determined by applying a nonlinear least squares fit to the data obtained with or without inhibitor. The kinetic parameters allowed the determination of the type of inhibition and of inhibition constants (Ki) of the various test bile acids. The data indicate that bile acids containing a 6- or 7-OH group exhibit competitive inhibition, whereas bile acids with no 6- or 7-OH group exhibit noncompetitive inhibition. Of the compounds exhibiting competitive inhibition, Ki varied with the number of hydroxyl groups on the sterol moiety. We conclude that the presence or absence of a 6- or 7-OH group dictates the mechanism of inhibition; the number of hydroxyl substituents determines the potency of competitive inhibition.
Intraluminal calcium modulates lipid dynamics of rat intestinal brush-border membranes
Authors: Dudeja P. K. , Brasitus T. A. , Dahiya R. , Brown M. D. , Thomas D. , Lau K.
Published: December 2017

The present investigations were performed to evaluate whether calcium modulates the physical state and lipid composition of rat enterocyte plasma membranes in vivo. Ca2+ [CaCl2 (50 mM) in NaCl] or NaCl (vehicle control) was administered to rats by intraluminal (gavage) or intraperitoneal routes. Sixty minutes later, brush-border (BBM) and basolateral membranes (BLM) were prepared from the proximal small intestine. By use of the fluorophores, DL-2-(9-anthroyl)-stearic acid (2-AS), DL-12-(9-anthroyl)-stearic acid (12-AS), and 1,6-diphenyl-1,3,5-hexatriene (DPH), steady-state fluorescence polarization studies demonstrated that intraluminal calcium decreased the fluidity of BBM but not BLM compared with their respective vehicle controls. These alterations in fluidity could, at least in part, be attributed to the concomitant increase in sphingomyelin content and the sphingomyelin/lecithin ratio (mol/mol) observed in the BBM prepared from calcium-gavaged rats. To evaluate the mechanism for these lipid alterations, enzyme activities involved in sphingomyelin synthesis and degradation were measured and revealed an increase in sphingomyelin synthase and a decrease in sphingomyelinase in BBM prepared from calcium-gavaged rats. In contrast, intraperitoneal administration of calcium failed to influence membrane fluidity, lipid composition, or these enzymatic activities in either BBM or BLM.
Does aspirin damage canine gastric mucosa by reducing its surface hydrophobicity?
Authors: Goddard P. J. , Hills B. A. , Lichtenberger L. M.
Published: December 2017

Intraluminally administered aspirin disrupts the gastric mucosal barrier in a pH-dependent manner and may do so by compromising the hydrophobic or nonwettable lining to the stomach. We examined the pH dependence and time-course of aspirin's effects on barrier integrity by measuring the aspirin-induced changes in surface wettability, potential difference (PD), and electrical resistance (R) of canine gastric mucosa mounted in Ussing chambers. Luminal surface hydrophobicity, as determined by contact angle (CA) measurements, and PD were reduced by acidic aspirin solutions but were not reduced by acidic solutions without aspirin (pH 2.6) or by aspirin solutions that were neutral or only mildly acidic (pH greater than 4.0). Significant reductions in CA were correlated well with the proportion of aspirin in its lipid-soluble undissociated form (r = 0.93, P less than 0.001). Acidified-aspirin solutions significantly reduced CA and PD after a 2.5-min incubation period. Significant reductions in R occurred 25 min after exposure to acidified aspirin. Morphological damage to the gastric epithelium was not apparent after a 5-min exposure to acidified aspirin but was conspicuous 30 min after aspirin treatment. Aspirin-induced reductions in CA were highly associated with decreases in mucosal PD in both the pH and time-dependent studies (r = 0.93 and r = 0.99, respectively, P less than 0.001). These data support the hypothesis that the undissociated form of aspirin compromises the protective nonwettable lining of the stomach and in doing so, disrupts the gastric mucosal barrier.
Participation of serotonin and substance P in the action of cholecystokinin on colonic motility
Authors: Wiley J. , Owyang C.
Published: December 2017

Cholecystokinin (CCK) has a potent stimulatory effect on gastrointestinal motility. The mechanism of CCK-generated contractions in the colon is unknown. We explored the possibility that CCK-mediated contractions in the guinea pig colon occur via a serotonin and/or substance P pathway. In the circular layer, octapeptide of CCK (CCK-8) had no effect under basal conditions, but after treatment with tetrodotoxin the peptide generated dose-dependent contractions (ED50 6 X 10(-8) M). In the longitudinal layer, CCK-8 produced dose-related contractions (ED50 6 X 10(-9) M) blocked by tetrodotoxin and markedly inhibited by the substance P antagonist, Spantide. The effect of substance P was not significantly antagonized by tetrodotoxin but was markedly attenuated by Spantide. Serotonin produced dose-dependent contractions in the longitudinal layer (ED50 4 X 10(-8) M). Desensitization to serotonin antagonized the action of CCK-8 but had no effect on substance P-mediated contractions. Pretreatment with the serotonin antagonist mianserin inhibited CCK-8- but not substance P-generated contractions. In contrast, the stimulatory effect of serotonin was antagonized by Spantide. These studies suggest that in the circular layer of the guinea pig colon CCK-8 has no effect under basal conditions, but after removal of tonic inhibition, the peptide produced a direct stimulatory effect. In contrast, CCK-8 generated contractions in guinea pig colon longitudinal layer, mediated by a pathway involving serotonin and substance P.
Role of ornithine decarboxylase in functional development of rat gastric mucosa
Authors: McNiel N. O. , Eikenburg B. E. , Johnson L. R.
Published: December 2017

The effects of inhibiting polyamine synthesis on the functional development of the gastric mucosa were studied in rats from 5 to 40 days old. They were treated from day 14 after birth with alpha-difluoromethylornithine (DFMO) at a concentration of 2% in the drinking water of mothers and pups. The rats were weaned on day 18. Basal acid and pepsin secretion, oxyntic gland mucosal pepsinogen content, and antral gastrin content followed similar developmental patterns in control animals. Levels of these parameters remained measurable but low until around the time of weaning, when dramatic log linear rises were observed. DFMO failed to delay the onset of the rises in any of these maturational indices. Ornithine decarboxylase (ODC) activity in the oxyntic gland mucosa was low but discernible in rats of every age studied. DFMO significantly reduced ODC activity at every age except 40 days, where there was no difference from control values. Our results suggest that ODC activity in the rat gastric mucosa does not change appreciably during neonatal development and that inhibiting putrescine synthesis from its precursor ornithine by DFMO treatment does not prevent or delay gastric mucosal maturation.
Effect of histamine, norepinephrine, and nerves on vascular pressures in dog liver
Authors: Lautt W. W. , Legare D. J.
Published: December 2017

In the control state, lobar venous pressure (LVP) measured proximal to a hepatic venous sphincter in dog liver (9.9 +/- 0.3 mmHg) is insignificantly different from portal venous pressure (PVP = 9.9 +/- 0.3 mmHg). Essentially all of the pressure drop occurs across the hepatic veins. Intraportal infusion of histamine constricts the hepatic venous sphincter and leads to similar elevations of LVP and PVP, indicating that all of the rise in PVP (except at small doses = 1 microgram X kg-1. min-1) can be accounted for by hepatic venous sphincter constriction. Norepinephrine at doses from 0.25 to 1.25 micrograms X kg-1. min-1 (intraportal) caused both hepatic venous sphincter constriction and constriction proximal to hepatic venous sphincters to roughly equal proportions, with approximately 44% of the rise in PVP due to hepatic sphincter constriction. Hepatic nerves activated both resistance sites, with 90% of the rise in PVP due to hepatic venous constriction at 2 Hz stimulation. By 4 Hz stimulation, the postsinusoidal sphincters were nearly maximally activated, but the “presinusoidal” resistance continued to increase until, at 10 Hz, the hepatic venous sphincter component accounted for only 59% of the rise in PVP. The proportion of PVP rise accounted for by hepatic venous sphincter resistance was not significantly altered by prior occlusion of the hepatic artery.
Taurocholate uptake by isolated skate hepatocytes: effect of albumin
Authors: Smith D. J. , Grossbard M. , Gordon E. R. , Boyer J. L.
Published: December 2017

Taurocholate transport was analyzed in a well characterized, polarized hepatocyte preparation from the small skate (Raja erinacea), an analbuminemic species that does not synthesize bile acids. In addition, the effect of sodium omission, bovine albumin, ovalbumin, and bovine gamma-globulin on the uptake of taurocholate was studied. Uptake could be divided into nonsaturable (0.48 pmol X min-1 X mg protein-1. microM-1) and saturable components (Km, 32.5 microM and Vmax 110 pmol X min-1 X mg protein-1). No evidence for sodium dependence could be obtained. Glycocholate competitively inhibited taurocholate uptake. The initial rate of taurocholate uptake was also inhibited by sulfobromophthalein, N-(4-azido-2-nitrophenyl)-2-aminoethyl sulfonate, and 4,4'-diisothiocyanostylbene-2,2'-disulfonic acid but not lactate or alanine. Hepatic uptake of taurocholate in albumin solutions (2.5%) was twice as great as expected from estimates of the free taurocholate concentration. In contrast, equimolar concentrations of ovalbumin or bovine gamma-globulin had no effect on measured rates of taurocholate uptake and no evidence for a specific albumin receptor could be found on these hepatocytes by 125I-albumin binding. These studies indicate that a carrier-mediated, sodium-independent transport system for taurocholate uptake is present in skate hepatocytes that is not driven solely by the free concentration of taurocholate.
Effects of neuromedin B and neuromedin C on exocrine and endocrine rat pancreas
Authors: Otsuki M. , Fujii M. , Nakamura T. , Tani S. , Oka T. , Yajima H. , Baba S.
Published: December 2017

Neuromedin B and neuromedin C are novel decapeptides that have recently been isolated from porcine spinal cord and canine intestinal mucosa and show striking sequence homology with bombesin and gastrin-releasing peptide (GRP-27) at the carboxyl-terminal region. The effects of synthetic neuromedin B and C on exocrine pancreatic function and insulin release have been compared with bombesin and GRP-27 in isolated pancreatic acini and isolated perfused pancreas in rat. Neuromedin B and C as well as bombesin and GRP-27 were able to cause stimulation of amylase release. The relative efficacy of neuromedin B, C, bombesin, and GRP-27 was the same as that of cholecystokinin octapeptide (CCK-8). Bombesin and GRP-27 were equipotent, and both were approximately 15-fold less potent than CCK-8. Neuromedin C was approximately 2-fold more potent, whereas neuromedin B as approximately 10-fold less potent than bombesin and GRP-27. All of these peptides stimulated insulin release that was limited to the first 3 min of a 20-min perfusion. However, GRP-27 and its related peptides were weak stimulants of insulin release compared with their abilities to stimulate exocrine pancreatic secretion. Bombesin and neuromedin B id not stimulate insulin release at doses stimulating pancreatic exocrine secretion. Neuromedin B was also approximately 10-fold less potent than neuromedin C, bombesin, and GRP-27 in eliciting insulin secretion. Because bombesin-like immunoreactivity is found to be present in nerves in the pancreas, neuromedin B and C may be neurotransmitters or neuromodulators and exert a direct local neurocrine action on enzyme secretion by acinar cells and insulin secretion by the islets.
Mechanism of pH effect on oleic acid and cholesterol absorption in the rat
Authors: Chijiiwa K. , Linscheer W. G.
Published: December 2017

Previous experiments [K. Chijiiwa and W. G. Linscheer, Am. J. Physiol. 246 (Gastrointest. Liver Physiol. 9): G492-G499, 1984] have shown higher rates of absorption of oleic acid (OA) and cholesterol (CH) from micellar solutions perfused through segments of small bowel at pH 5.5 than at pH 6.5. Both solutions contained equal amounts of these lipids in addition to sodium taurocholate (30 mM). It was hypothesized that there may be two reasons to explain this observation. First, the micelles of one of the two solutions (pH 6.5) became depleted of these lipids during the perfusion procedure, while the micelles of the other solution (pH 5.5) were kept saturated with these lipids by the presence of emulsified particles in the perfusate. Second, the pH difference resulted in a much lower ratio of protonated vs. ionized OA in the pH 6.5 solution. Most investigators assume that primarily protonated fatty acid (FA) is absorbed and very little ionized FA is absorbed. The purposes of the present study are to evaluate further the factor of lipid saturation of the micelles by comparison of rates of absorption from two partially lipid-depleted micellar solutions containing equal amounts of OA and CH, in which the micelles of one solution were much more lipid depleted than the micelles of the other. This was caused by the pH difference. The second purpose is to evaluate the effect of the pH-related difference in protonate vs. ionized OA on absorption of OA from nonmicellar aqueous solutions.(ABSTRACT TRUNCATED AT 250 WORDS)
Manometry of canine ileocolonic sphincter: comparison of sleeve method to point sensors
Authors: Quigley E. M. , Dent J. , Phillips S. F.
Published: December 2017

Tonic and phasic pressures at the canine ileocolonic sphincter (ICS) were recorded by a manometric assembly that combined a sleeve sensor with multiple side-hole pressure ports. By aligning the side holes precisely it was possible to evaluate in vivo the fidelity of the sleeve relative to simultaneous pressure records from the point sensors. The ICS exhibited tonic and phasic pressures, often in excess of 100 cmH2O of pressure. The sleeve sensor was tolerant of small, but potentially important, movements of the assembly relative to the ICS. Point sites of recording moved in and out of the high-pressure zone and side holes were, therefore, not ideal sensors of sphincteric tone. The anticipated properties of this sleeve, that it would display reduced fidelity for rapid changes in pressure at sites away from its point of perfusion, were confirmed in vivo. The sleeve also “summarized” phasic bursts and was unable to monitor propagation of such events. However, the combined assembly proved excellent for examining overall function of the canine ICS.
Transepithelial transport of glutathione in vascularly perfused small intestine of rat
Authors: Hagen T. M. , Jones D. P.
Published: December 2017

We used an in situ closed-loop vascular perfusion of rat small intestine to see whether intact glutathione (GSH) was transported from the lumen into the mesenteric circulation. Results using [3H] GSH showed radiolabel appearance in the perfusate, and high-performance liquid chromatography analysis confirmed that the transported radiolabeled species was intact GSH. Transepithelial transport was Na+ dependent, where Na+-free solutions on the luminal side inhibited transport but in the vasculature stimulated transport. Transport was inhibited by the GSH analogues ophthalmic acid and gamma-glutamylglutamate when added to the lumen. Probenecid caused inhibition only when added on the vascular side, suggesting that the transport systems on the two poles of the cells may be different. In vivo studies with GSH administration via stomach gavage caused marked increases in plasma GSH concentrations. These results establish that transepithelial transport of intact GSH occurs in rat small intestine. This process may allow dietary or biliary derived GSH to be utilized by various cell types that can take up intact GSH from the plasma. Moreover, the results show that oral administration of GSH may be therapeutically useful.
Sodium-independent, bicuculline-sensitive [3H]GABA binding to isolated rat hepatocytes
Authors: Minuk G. Y. , Bear C. E. , Sarjeant E. J.
Published: December 2017

To determine whether hepatocytes possess specific receptor sites for gamma-aminobutyric acid (GABA), a potent amino acid neurotransmitter, [3H]GABA, was added to sodium-free suspensions of Percoll-purified hepatocytes derived from collagenase-perfused rat livers under various experimental conditions and in the presence or absence of specific GABA receptor agonists (muscimol) and antagonists (bicuculline). The effects of GABA, muscimol, and bicuculline on hepatocyte resting membrane potentials were also determined. Specific binding of [3H]GABA to hepatocytes was a consistent finding. GABA-hepatocyte interactions were reversible and temperature dependent. Muscimol and bicuculline inhibited binding in a dose-dependent manner (IC50, 30 nM and 50 microM, respectively), whereas strychnine (1.0-100 microM), a nonspecific central nervous system stimulant, had no appreciable effect. Both GABA and muscimol (100 microM) caused significant hyperpolarization of hepatocyte resting membrane potential (delta PD 5.4 +/- 3.1 and 22.2 +/- 16.2 mV, respectively, means +/- SD, P less than 0.0005). Bicuculline (100 microM) inhibited the effect of muscimol (P less than 0.05). The results of this study suggest that specific GABA receptor sites exist on the surface of isolated rat hepatocytes. The presence of such sites raises the possibility that, in addition to adrenergic and cholinergic innervation, hepatic function may be influenced by GABA-ergic neurotransmitter mechanisms.
Development of gastrointestinal surface. VIII. Lectin identification of carbohydrate differences
Authors: Pang K. Y. , Bresson J. L. , Walker W. A.
Published: December 2017

Binding of microvillus membranes (MVM) from newborn and adult rats by concanavalin A (Con A), Ulex europaeus (UEA I), Dolichos bifluorus (DBA), and Triticum vulgaris (WGA) was examined to determine the availability of carbohydrate-containing sites for these lectins on the intestinal surface during development. Consistent patterns of differences in the reaction of MVM with these lectins were found. Con A and UEA had much higher reactivities to MVM of adult than newborn rats. 125I-labeled-UEA gel overlay experiments revealed the abundance of UEA-binding sites in MVM of adult rat in contrast to the two binding sites in MVM of a newborn rat. DBA bound only to MVM of the adults, and very few binding sites were found in immature MVM. In contrast to these lectins, WGA binding was much higher in MVM of the newborns and decreased with maturation. Additional experiments on the age dependence of UEA and DBA reactivities revealed that the most striking changes occur in animals from 2 to 4 wk of age. In MVM from 2-wk-old rats, there were only 13.9% and less than 0.2% of the adult binding capacities for UEA and DBA, respectively. By the time the animals were 4 wk old, the binding capacity for UEA had attained close to the level of the adults, whereas for DBA it reached 71.3% of the adult value. These results provide definite evidence of changes in the intestinal surface during perinatal development.
Intracellular chloride activity in intact rat liver: relationship to membrane potential and bile flow
Authors: Fitz J. G. , Scharschmidt B. F.
Published: December 2017

Active chloride transport has been described in a variety of epithelia, and intracellular chloride activity (aiCl) in these tissues is generally elevated twofold or more above the level predicted for passive diffusion. To determine whether active chloride transport might contribute to canalicular bile formation, we have used conventional and Cl- -selective microelectrodes to measure aiCl of rat hepatocytes in vivo under a variety of conditions. Under basal conditions, the membrane potential difference averaged -33.2 +/- 3.5 mV (means +/- SD) in 29 animals, and the ratio (R) of observed aiCl (24.8 mM) to that expected for passive distribution at this membrane potential (22.6 mM) was 1.10 +/- 0.08, a value slightly but significantly greater than that predicted for passive distribution. Infusion of alanine (45-mumol bolus, 10.8-mumol/min infusion) in 5 animals hyperpolarized the membrane potential to -43.6 +/- 4.0 mV over 10-15 min and resulted in a significant fall in aiCl to 15.1 +/- 4.8 mM but with no change in R. Infusion of theophylline (577 nmol/min), taurocholate (3-mumol bolus, 810-nmol/min infusion), and ursodeoxycholic acid (4-mumol bolus, 2.13-mumol/min infusion) into 5 animals each increased bile flow by 6.1, 34.1, and 96.8%, respectively, compared with saline-infused controls but did not alter membrane potential or chloride distribution. These observations indicate that aiCl is close to the level predicted for passive distribution under basal conditions, after hyperpolarization of the membrane potential by alanine, and after stimulation of bile flow by a variety of choleretics. By analogy with Cl- -secreting epithelia, it appears unlikely that active chloride transport across the basolateral membrane contributes significantly to canalicular bile formation by the hepatocyte.
Proteins are secreted from heterogeneous prestored sources in the exocrine pancreas
Authors: Miller P. E. , Adelson J. W.
Published: December 2017

Recent studies demonstrating nonparallel regulated secretion of prestored digestive enzymes in tightly linked groups consistent with the exocytosis mechanism led us to predict that digestive enzymes would be found to be secreted from heterogeneous sources within the exocrine pancreas (J. W. Adelson, and P.E. Miller, Science Wash. DC 228: 993-996, 1985). We explored whether the gland was heterogeneous with respect to its sources of prestored secretory proteins with a double isotopic label method not dependent on activity of secreted digestive enzymes. Rabbit pancreatic proteins were double labeled in vivo by injection of each animal with chemically identical but isotopically distinct mixtures of 3H- and 14C-labeled amino acids, which were administered separately or together on consecutive days after partial depletion of prestored proteins by administration of cholecystokinin (CCK), methacholine chloride, or saline in a protocol in which order of both isotope and secretagogue administration was varied. Three days after labeling, proteins were recovered by collection from cannulated pancreatic ducts of anesthetized animals after stimulation with alternating increasing doses of CCK and methacholine chloride. Pooled secretory data were analyzed to determine whether secretagogue pretreatment resulted in specific and heterogeneous sequestration of proteins after synthesis; data after final secretory stimulation with methacholine chloride and CCK were individually analyzed to determine whether presequestered proteins were mobilized from heterogeneous compartments during secretion. Correlation and regression analysis of isotopic outputs and variance analysis of specific radioactivities of secreted proteins showed sequestration into and secretion from heterogeneous pools of secretory proteins, directly confirming out hypothesis. These results provide a cell biological mechanism explaining regulated nonparallel secretion of digestive enzymes.
Apolipoprotein A-IV synthesis in rat intestine: regulation by dietary triglyceride
Authors: Apfelbaum Terri F. , Davidson Nicholas O. , Glickman Robert M.
Published: December 2017

Page G662: Terri F. Apfelbaum, Nicholas O. Davidson, and Robert M. Glickman. “Apolipoprotein A-IV synthesis in rat intestine: regulation by dietary triglyceride.” Page G663: sentence beginning on line 10, second column, should read “Data are expressed as mean ± 1 SD, and comparisons for both paired and unpaired means were made by Students t test.”