bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of 1,25-dihydroxyvitamin D3 on colonic calcium transport in vitamin D-deficient and normal rats
Authors: Favus M. J. , Langman C. B.
Published: December 2017

To determine whether prior vitamin D intake influences the intestinal calcium absorptive action of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], we measured in vitro the two unidirectional transepithelial fluxes of calcium across descending colon segments from rats fed either a vitamin D-deficient or normal diet and injected with either 10, 25, or 75 ng of 1,25(OH)2D3 or vehicle alone. Vitamin D deficiency abolished net calcium absorption [J net, -2 +/- 2 vs. 12 +/- 2 (SE) nmol X cm-2 X h-1, P less than 0.001], and 10 ng of 1,25(OH)2D3 raised J net to levels found in normal rats. Larger doses (25 and 75 ng) increased J net above levels in normal rats given the same dose. In normal rats only 75 ng of 1,25(OH)2D3 increased calcium J net above vehicle control values (12 +/- 2 vs. 38 +/- 4 nmol X cm-2 X h-1, P less than 0.001). Circulating 1,25(OH)2D3 measured by radioreceptor assay was well correlated with calcium transport. For each dose of 1,25(OH)2D3 higher serum 1,25(OH)2D3 levels were reached in vitamin D-deficient rats. Only the 75-ng dose increased circulating 1,25(OH)2D3 and colonic calcium transport in normal rats. Intravenous [3H]-1,25(OH)2D3 disappeared more rapidly from the circulation of normal rats, suggesting that accelerated metabolic degradative processes for 1,25(OH)2D3 may be present in normal but not in vitamin D-deficient rats and may account for the lack of a biological response to 1,25(OH)2D3 in normal animals.
Invariant relation between total acid secretion and secretagogue exposure: secretory dynamics in bullfrog
Authors: Ekblad E. B. , Licko V.
Published: December 2017

Using a continuous recording of acid secretion in frog gastric mucosa by pH-stat interfaced with a microcomputer, the pattern of secretion rate was studied under variable concentrations and durations of stimulation by histamine and forskolin. This tissue can respond with only a limited range of secretory rates. Larger concentrations and/or longer durations of stimulation may result in a secretion rate pattern prolonged far beyond the duration of stimulation. Although for the concentration-response curve the steady-state or peak acid secretion varies with the duration of stimulation, total acid secreted as a function of exposure to stimulator (time integral of the stimulatory pattern) is independent of the stimulatory pattern.
Canine interdigestive and postprandial gallbladder motility and emptying
Authors: Traynor O. J. , Dozois R. R. , DiMagno E. P.
Published: December 2017

The objectives of this study were to characterize intraluminal gallbladder pressure during fasting and postprandially and to determine the relationships between its intraluminal pressure and emptying. Conscious dogs, with chronic indwelling gallbladder and duodenal catheters to measure pressures and infuse nonabsorbable markers, were used to quantify intraluminal pressures and emptying of gallbladder contents and bile into the duodenum during interdigestive and postprandial periods. During the interdigestive period, a brief rise in intragallbladder pressure followed by the flow of bile and 20% of gallbladder marker into the duodenum occurred only during phase II (a period of irregular duodenal contractility preceded by absent duodenal activity, phase I, and followed by a period of regular duodenal contractility, phase III). We suggest that intragallbladder pressure increased secondary to contraction of the gallbladder against a closed sphincter of Oddi and its decline to base line was accompanied by sphincter relaxation, partial gallbladder emptying, and flow of bile into the duodenum. Postprandially, intragallbladder pressure transiently increased and was followed by an isotonic phase lasting 74 +/- 12 min that ended with the onset of rhythmic large-amplitude pressure elevations that continued for 5.1 +/- 1.6 h. Gallbladder emptying was most rapid during the first 30 min postprandially and was completed by 2 h. Thereafter, large-amplitude gallbladder pressure elevations may prevent gallbladder filling and divert hepatic bile into the duodenum until return of the fasting pattern.
Activation of protein kinase activity in pancreatic acini by calcium and cAMP
Authors: Burnham D. B. , Williams J. A.
Published: December 2017

Regulation of protein kinase activity by calcium and cAMP was investigated in cytosolic and particulate preparations from isolated mouse pancreatic acini. In cytosol, three protein kinase activities could be distinguished: a calcium-activated kinase activity that was increased by exogenous calmodulin (CaM) and abolished by treatment of cytosol with a phenothiazine-coupled resin, a calcium-activated kinase activity dependent on phosphatidylserine (PS), and cAMP-activated kinase activity. Phosphorylation of a Mr = 92,000 cytosolic protein was greatly increased by both CaM-dependent and cAMP-activated kinases, whereas PS-dependent kinase activity most heavily phosphorylated proteins of Mr = 62,000 and 40,000. In addition, these kinase activities demonstrated differences in specificity for exogenous protein substrates. CaM-and PS-dependent kinases were completely blocked by trifluoperazine; the inhibitor protein of cAMP-activated protein kinase selectively inhibited cAMP-activated kinase activity. Exogenous CaM decreased the concentration of free calcium for half-maximal activation of CaM-dependent kinase activity from 5.5 +/- 0.5 to 1.2 +/- 0.3 microM Ca2+; half-maximal activation of the PS-dependent and cAMP-activated kinase activities was achieved at 12 microM Ca2+ and 40-50 nM cAMP, respectively. In a particulate fraction depleted of endogenous CaM, CaM-dependent and cAMP-activated kinase activities were detected. In conclusion, this study demonstrates the existence of protein kinases in pancreatic acini which may be involved in the action of pancreatic regulatory agents that use calcium or cAMP as an intracellular messenger.
Intestinal transport of 5-methyltetrahydrofolate
Authors: Selhub J. , Powell G. M. , Rosenberg I. H.
Published: December 2017

The mechanism of intestinal absorption of 5-methyltetrahydrofolate (5- CH3THF ) has been the topic of some controversy. In the present study, we have used enzymatically prepared 5- CH3THF to characterize transport by rat intestinal loops in vivo and everted jejunal sacs in vitro. Transport of 5- CH3THF is saturable (Km = 5.2 microM) and highly pH dependent, with the rate of maximal transport occurring at pH 5.8. Transport is competitively inhibited by folic acid (Ki = 4.2 microM) and methotrexate (Ki = 4.65 microM). Metabolic poisons and anaerobiosis greatly reduce 5- CH3THF transport. We conclude that 5- CH3THF transport in the rat intestine occurs by the same structure-specific mechanism responsible for the transport of unreduced folic acid and other monoglutamyl folates.
Effect of vitamin D3 on duodenal calcium absorption in vivo during early development
Authors: Dostal L. A. , Toverud S. U.
Published: December 2017

The effect of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and vitamin D deficiency on duodenal calcium absorption in suckling and weaned rats was determined by an in situ loop technique. In vitamin D-replete (+D) rats, the linear, or nonsaturable, component of calcium absorption was very efficient in 14-day-old pups and decreased with age until 35 days. The saturable component, which was undetectable in 14-day-old pups, became detectable by 18 days of age and increased until 26 days of age. Calcium absorption was not reduced in vitamin D-deficient (-D) 14-day-old pups as compared with +D pups. A high dose of 1,25(OH)2D3 increased the plasma calcium level of +D suckling rats but had no effect on calcium absorption even with milk present in the loop. Weaned -D rats had a reduced saturable component of absorption (P less than 0.01) compared with +D rats. A high dose of 1,25(OH)2D3 significantly increased calcium absorption and plasma calcium levels of -D rats. Our results indicate that during suckling calcium absorption occurs by a process that is insensitive to vitamin D. After weaning both saturable and nonsaturable processes appear to contribute to calcium absorption, and the saturable component can be influenced by vitamin D status or a high dose of 1,25(OH)2D3.
Voltage clamping induces resistance and current-voltage plot changes in frog gastric mucosa
Authors: Kidder G. W. , Elrod M. G.
Published: December 2017

Changing the potential across the isolated frog gastric mucosa by voltage clamping changes the measured resistance of the tissue in two ways. An immediate change in resistance results from changing the measuring position on the nonlinear current-voltage (I-V) plot. Subsequent to this, the resistance changes slowly with a half-time of about 3 min, a change that is not predicted by a previous model for voltage transients and that implies slow changes in membrane resistance following changes in intracellular ion content. The I-V plot over the range examined shows three breakpoints; changing clamp voltage alters the position of two of these breakpoints as well as the slope of the connecting resistances. The central breakpoint agrees with the potential at zero current and varies with it as the clamp potential is changed, as predicted from a diode model for breakpoint generation.
Effect of topical histamine on mucosal microvascular permeability and acid secretion in the rat stomach
Authors: Nagata H. , Guth P. H.
Published: December 2017

The effect of topical histamine on microvascular permeability to macromolecules was studied in the rat gastric mucosa using a fluorescent in vivo microscopy technique. Acid secretion was measured in the pylorus-ligated rat. A topical dose of 10(-2)M histamine increased acid output to a maximum, which was equal to the maximum values attained by intravenous or subcutaneous histamine. Only in rats pretreated with a beta-adrenergic antagonist did 10(-2) to 5 X 10(-2)M histamine cause leak of a fluorescein-albumin conjugate from mucosal microvessels. Leak occurred around collecting venules but not from capillaries. An H1-receptor antagonist, but not an H2-receptor antagonist, significantly decreased histamine-induced leaks. We concluded the following. 1) topically applied histamine penetrates into the mucosa and can increase acid secretion to the same extent as parenteral histamine. 2) Topical histamine increases microvascular permeability to macromolecules only when beta-adrenergic receptors are blocked. Larger doses of histamine are needed for initiating the permeability change than for initiating the acid secretory response. 3) H1-receptors in venules are involved in the histamine-induced increase in permeability.
Direct measurement of duodenal acid-pepsin exposure at site of ulceration in rats
Authors: Gallagher G. T. , Szabo S.
Published: December 2017

A new technique for the preparation of a chronic duodenal fistula in the rat is described. The effect of cysteamine and propionitrile on the acidity of duodenal contents was studied, and the degree of acidity correlated with the respective duodenal ulcerogenicity of these two compounds. After subcutaneous administration of cysteamine, reduced duodenal acid was seen for 2-4 h, followed by large increases continuing up to 12 h and declining thereafter. Oral cysteamine administration produced acid increases of rapid onset and shorter duration, accompanied by increased pepsin activity. The weak duodenal ulcerogen propionitrile did not affect duodenal acidity. Cimetidine markedly reduced the duodenal acidification induced by cysteamine, whereas the dopamine agonist bromocriptine did not affect acid delivery to the duodenum but reduced the pepsin activity in the duodenal contents by 50%. The duodenal fistula rat provides a new model system for studies on the pathogenesis of experimental duodenal ulcer.
Lower esophageal sphincter function in the cat: role of central innervation assessed by transient vagal blockade
Authors: Reynolds R. P. , El-Sharkawy T. Y. , Diamant N. E.
Published: December 2017

Studies were performed on four cats to assess the role of extrinsic vagal innervation in the control of lower esophageal sphincter (LES) function. Both cervical vagal nerves were blocked transiently by cooling. LES pressure was measured using a multilumen manometry tube. LES relaxation was assessed during intraesophageal balloon distension in both the striated and smooth muscle portions of the esophagus. Bilateral vagal nerve blockade lowered the mean LES pressure from 58 +/- 17 to 29 +/- 9 mmHg (P less than 0.01). During vagal blockade, balloon distension in the striated muscle esophagus further reduced sphincter pressure to 16 +/- 4 mmHg (P less than 0.01) and that in the smooth muscle esophagus to 15 +/- 3 mmHg (P less than 0.01). Swallow-induced LES relaxation was abolished during bilateral vagal nerve blockade. During vagal blockade, atropine reduced LES pressure to 10 +/- 1 mmHg, phentolamine to 13 +/- 6 mmHg, and hexamethonium to 10 +/- 4 mmHg (all P less than 0.01). We conclude that 1) normal LES tone in the cat is mediated primarily by two separate neural mechanisms: a vagal cholinergic mechanism and a nonvagal mechanism that utilizes both alpha-adrenergic and cholinergic receptors; 2) local, intramural mechanisms of high threshold are present in the striated and smooth muscle cat esophagus to allow distension-induced reflex inhibition of the LES; and 3) swallow-induced LES relaxation is dependent on vagally mediated central nervous system connections.
Enzymic development of the small intestine: are glucocorticoids necessary?
Authors: Martin G. R. , Henning S. J.
Published: December 2017

The aim of this study was to determine the extent to which the postnatal maturation of intestinal hydrolases in the rat is dependent on the developmental rise of circulating corticosterone that occurs at the end of the 2nd wk of life. Pups were adrenalectomized (adX) on day 9 (i.e., before the developmental surge of corticosterone begins) and were killed on days 17, 20, 23, and 26. Serum corticosterone was measured to eliminate any incompletely adX animals. The rates of the developmental increases of sucrase and maltase activities and the developmental decreases of lactase and acid beta-galactosidase activities were depressed in adX pups aged 23 days and younger as compared with sham-operated controls. Administration of corticosterone (10 micrograms X g body wt-1 X day-1) to adX pups restored the developmental changes of these enzyme activities to rates equal to or greater than those in the sham-operated pups. By 26 days of age, all four enzyme activities of adX pups had reached their normal ontogenic plateau. We conclude that adrenal corticosteroids are potent determinants of the rate of developmental changes of intestinal hydrolases but that these hormones are not necessary for enzymes to eventually reach adult activities.
Mechanisms of H+ injury in rabbit esophageal epithelium
Authors: Orlando R. C. , Bryson J. C. , Powell D. W.
Published: December 2017

We previously postulated that active Na transport by the esophageal stratified squamous epithelium is important for maintenance of its barrier function. To investigate this further we studied the effects of HCl on the in vivo esophageal potential difference (PD), on in vitro Na transport, and on esophageal Na-K-ATPase activity. In vivo esophageal perfusion with low concentrations of HCl (20 or 40 mM) increased the PD and a high concentration (120 mM) decreased it. An intermediate concentration (80 mM) caused a biphasic response with an initial increase in PD followed by a progressive decrease in PD. In vitro transport studies were performed to explain the increased in vivo PD. In the presence of luminal H+ the increased PD resulted from H+ diffusion from lumen to blood, whereas after H+ exposure the increased PD was due largely to increased net Na transport from lumen to blood through an amiloride-sensitive mechanism. In tissues with prolonged exposure to 80 mM HCl (PD decreased 80-100%), Na-K-ATPase activity was significantly inhibited (1.94 +/- 0.32 vs. 5.12 +/- 0.73 mumol P X mg prot-1 X h-1). Thus, HCl initially increases the in vivo esophageal PD by H+ transport from lumen to blood, a process replaced by stimulated net Na transport when H+ is replaced by Na. Prolonged acid exposure ultimately decreases Na exit from cells by inhibiting Na-K-ATPase activity. This sequence suggests that alterations in Na transport could result in cell edema and necrosis via loss of cell volume regulation.
Role of dietary iron in maturation of rat small intestine at weaning
Authors: Buts J. P. , Delacroix D. L. , Dekeyser N. , Paquet S. , Horsmans Y. , Boelens M. , Van Craynest M. P. , De Meyer R.
Published: December 2017

The weanling process is characterized by the transition from a liquid diet poor in iron (rat milk) to a solid diet high in iron (chow pellets). To examine the effects of iron content of the weanling diet on terminal maturation of rat small intestine, suckling pups, nursed by iron-sufficient mothers, were weaned by day 16 onto a solid basal diet that was either deficient [low-iron diet (LID): 0.5 mg iron/100 g solid] or high [high-iron diet (HID) controls: 30 mg iron/100 g solid] in iron. The animals were studied during or at the end of the 4th postnatal wk. By day 17 rats weaned onto the LID exhibited an initial rise in jejunal sucrase activity as did their controls, but the activity plateau of the enzyme was reduced to a level 60% of the controls. On day 28 iron-deprived rats were anemic and showed significant decreases (P less than 0.01 compared with HID rats) in the activity of jejunal sucrase (-57%), neutral lactase (-83%), and maltase (-46%), whereas villus height, crypt depth, mucosal mass parameters, ileal acid beta-galactosidase activity, mucosal protein, and DNA synthesis rates were equivalent in LID and HID groups. The concentration of the secretory component, a glycoprotein synthesized by the intestinal crypt cell, was markedly depressed (P less than 0.01 vs. controls) in the jejunum (-54%) and ileum (-79%) of iron-deprived rats. When D-[1-14C]glucosamine was injected intraperitoneally, incorporation of the label into jejunal and ileal brush-border proteins was two to three times lower for iron-deficient rats than for controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Association between HCO3(-) absorption and K+ uptake by Amphiuma jejunum: relations among HCO3(-) absorption, luminal K+, and intracellular K+ activity
Authors: Imon M. A. , White J. F.
Published: December 2017

Titration techniques and K+- sensitive microelectrodes have been used to investigate the relations among HCO3(-) absorption, luminal K+, and intracellular K+ activity in in vitro Amphiuma jejunum. The HCO3(-) absorptive flux (JHCO3(-] measured by pH-stat under short circuit was reduced by removal of K+ from the medium but not by replacement of Na+ with choline. JHCO3(-) exhibited a seasonal variation when K+ was absent from the media and was increased to a maximum when K+ equaled 5 mM. Addition of K+ to a K+-free luminal medium stimulated JHCO3(-) much more than addition to the serosal medium. Acetazolamide (10(-4) M) blocked K+-stimulated HCO3(-) absorption while benzolamide reduced the short-circuit current associated with HCO3(-) absorption much more rapidly when added to the mucosal bathing medium. Intracellular K+ activity (aik) and mucosal membrane potential (psi m) of jejunal villus cells were measured with double-barreled microelectrodes. When bathed bilaterally with HCO3(-)-containing media, K+ was actively accumulated for many hours (aik = 58.5 mM) but in the presence of ouabain fell to equilibrium (16 mM) after 2 h. In contrast, when HCO3(-) absorption was induced by removal of serosal HCO3(-), aik was elevated to 83.6 mM and, after 4-h exposure to ouabain cell K+, remained far above electrochemical equilibrium at 33 mM. Tissues bathed in Na+-free (Tris) media containing ouabain retained cell K+ after 4 h at even higher levels (46 mM). Cell K+ activity was reduced by removal of K+ from either the mucosal or serosal medium. Acetazolamide reduced aik over 2 h in Na+-free media from 66 to 42 mM. The decline in aik was associated with a concomitant decline in the HCO3(-) absorptive current. It is concluded that K+ is actively accumulated across both luminal and serosal membranes of the jejunal absorptive cell and that the luminal uptake mechanism is linked to HCO3(-) absorption or an equivalent process.
Secretion of colonic isozyme of lysozyme in association with cecotrophy of rabbits
Authors: Camara V. M. , Prieur D. J.
Published: December 2017

The relation between the rabbit gastrointestinal (colonic) isozyme of lysozyme and the unique circadial coprophagic behavior of rabbits, termed "cecotrophy," was investigated. We found that lysozyme activity was very low in all segments of the rabbit gastrointestinal tract proximal to the fusus coli. However, the distal or nonsacculated colon, located distal to the fusus coli, had very high lysozyme activity throughout. It was determined, furthermore, that the lysozyme in the wall of the nonsacculated colon was secreted circadially into the colonic lumen in association with the circadial production of soft feces that were destined for reingestion by cecotrophy. The colonic lysozyme, therefore, was transferred to the stomach. These observations suggest that rabbit colonic lysozyme may have a possible function in the upper gastrointestinal tract and be analogous to ruminant abomasal-duodenal lysozyme.
Mechanisms of motility changes during acute intestinal obstruction in the dog
Authors: Prihoda M. , Flatt A. , Summers R. W.
Published: December 2017

We investigated the effects of autonomic drugs and the role of intestinal contents on the motility changes that occur during acute obstruction. Myoelectric activity was recorded from seven electrodes spaced at 3-cm intervals along the midjejunum of nine conscious dogs. Another animal had electrodes evenly placed throughout the small bowel. Obstruction was created by inflation of an intraluminal balloon. Systemic arterial blood pressure and pulse rate were monitored. Initially, motor activity of the small intestine increased proximal to an acute intestinal obstruction and decreased distally. Recordings from the entire small intestine revealed that these effects occurred almost immediately in the region of the obstruction but not at more distant sites. Within 2-3 h, however, proximal hypermotility had extended to the duodenum and distal inhibition had progressed to the terminal ileum. Diversion of intestinal contents without obstruction reduced myoelectric activity distal to the site of drainage. However, reinfusion of chyme distal to the site of obstruction failed to restore inhibited motor activity to control levels. Atropine sulfate (50 micrograms/kg) decreased and neostigmine (5 micrograms X kg-1 X min-1) potentiated the hyperactivity proximal to the obstruction, but neither agent significantly affected the distal inhibition. Phentolamine (1 mg/kg) and propranolol (1 mg/kg) had no effect on proximal or distal motor activity during obstruction; these were doses that blocked cardiovascular responses to adrenergic agonists. These results suggest that changes in luminal contents and in nervous activity both contribute to the intestinal motility changes that accompany obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)
Electrical properties and synaptic connections to neurons in parasympathetic colonic ganglia of the cat
Authors: Krier J. , Hartman D. A.
Published: December 2017

Intracellular recording techniques were used in vitro to analyze the electrophysiological properties and synaptic connections to cat parasympathetic neurons in ganglia located on the serosal surface of the distal colon. Neurons were classified into two types. The first type exhibited spontaneous action potentials at regular and irregular interspike intervals. Spontaneous action potentials were 1) not abolished by superfusion of the ganglia with a modified Krebs solution containing low Ca2+, high Mg2+, or nicotinic ganglionic blocking agents, 2) reduced or abolished by intracellular injection of hyperpolarizing current, and 3) increased by intracellular injection of depolarizing current. We suggest that the generation of spontaneous action potentials may be due to an endogenous depolarizing mechanism and not to cholinergic synaptic input from other neurons located in the ganglia. The second type of neuron termed "quiescent" exhibited a stable transmembrane potential and elicited action potentials in response to electrical stimulation of nerve trunks. Both quiescent and spontaneously discharging neurons receive synaptic input from preganglionic fibers in the pelvic nerve and project their postganglionic axons to colonic nerve fibers that innervate effector structures in the colon.
Effects of hindbrain stimulation on lower esophageal sphincter pressure in the cat
Authors: Barone F. C. , Lombardi D. M. , Ormsbee H. S.
Published: December 2017

Lower esophageal sphincter (LES) pressure was measured in anesthetized cats during electrical stimulation of the dorsal motor nucleus of the vagus (DMV) and nucleus ambiguus (NA). Stimulation parameters were varied to determine maximal changes in LES pressure and upper gastrointestinal motor responses. LES pressure decreased significantly during DMV and NA stimulation. The LES preferentially was affected over other upper gastrointestinal locations. Bradycardia and increases in blood pressure occurred with stimulation of both nuclei. LES pressure changes could be demonstrated in the absence of other gastrointestinal responses by decreasing hindbrain stimulation parameters. Cervical vagotomy completely eliminated hindbrain stimulation-induced changes in LES pressure, upper gastrointestinal motor activity, and heart rate. Similar frequency-LES pressure response relationships were observed for DMV and NA stimulation, with maximum changes occurring at 25 Hz. Changes in LES pressure occurred at shorter stimulation pulses (0.05 vs. 0.5 ms) and at lower stimulating current strength (30 vs. 60 microA) during DMV as compared with NA stimulation. In addition, stimulation of areas adjacent to the DMV and NA also significantly altered LES pressure, indicating that a large portion of the cat hindbrain associated with the vagal motor nuclei is involved in LES pressure control.
In vivo zinc transport by rat small intestine after extensive small bowel resection
Authors: Urban E. , Campbell M. E.
Published: December 2017

We studied the effects of intestinal resection on in vivo zinc transport and intestinal tissue zinc in remnant duodenum and ileum 4 wk after two-thirds small bowel enterectomy. In situ duodenal and ileal intestinal segments from resected and sham-operated control rats were perfused through the lumen with an isotonic solution containing 0.077 mM zinc with isotopic 65Zn as tracer. After resection there was significant mucosal growth in both segments, but segment transport specific activities (transport per gram mucosa) were unchanged. Therefore, increased segment transport capacities (transport per centimeter segment length) in both segments approximated increased mucosal mass. Comparisons with transport data from our earlier studies on other luminal substrates in rats after small bowel resection showed that adaptive transport mechanisms vary not only with the luminal substrate examined but may also differ in remaining proximal and distal small bowel. In the present study about 12% of the absorbed radiotracer zinc remained in the intestinal wall after perfusion of both duodenum and ileum of resected and control animals, and there were no effects of resection on tissue radiotracer 65Zn concentrations or specific activities in the mucosal fraction or underlying tissues. Calculations of mucosal entry and exit fluxes per centimeter segment length showed that the major effect of resection was to increase the zinc entry flux at the luminal surface of the mucosa. At the basal surface of the mucosa, both entry and exit fluxes increased.(ABSTRACT TRUNCATED AT 250 WORDS)
Pepsinogen secretion from dispersed chief cells from guinea pig stomach
Authors: Raufman J. P. , Sutliff V. E. , Kasbekar D. K. , Jensen R. T. , Gardner J. D.
Published: December 2017

In the present study we examined the actions of various secretagogues on pepsinogen secretion from freshly dispersed chief cells prepared from guinea pig stomach. Chief cells were obtained by preparing dispersed gastric glands, subjecting the glands to mechanical disruption in the presence of EGTA, and fractionating the resulting mucosal cells on a Percoll density gradient. Chief cells constituted 90% of the final cell suspension and cell viability was 99%. In these cells, pepsinogen secretion was stimulated by agents whose actions are probably mediated by calcium: carbachol, cholecystokinin, and A23187. Pepsinogen secretion was also stimulated by agents whose actions are probably mediated by cAMP: secretin, vasoactive intestinal peptide, and 8-bromo-cAMP. Reducing the incubation temperature from 37 degrees to 4 degrees C or adding carbonyl cyanide m-chlorophenylhydrazone abolished secretagogue-induced pepsinogen secretion. These results indicate that freshly dispersed chief cells from guinea pig stomach are responsive to secretagogues and provide a suitable model for investigating cellular mechanisms of secretagogue-induced pepsinogen secretion.
Role of prostaglandins in regulating gastric motility
Authors: Sanders K. M.
Published: December 2017

Muscles of the stomach possess the ability to synthesize several prostaglandins. These compounds function as local regulatory agents by influencing the motor performance of the muscle cells. In the distal stomach the dominant effect of endogenous prostaglandins is to decrease the amplitude of contractions and decrease the ability of the muscles to respond to excitatory stimuli. Prostaglandins also have a chronotropic role in the distal stomach, and they are responsible for the frequency effect of gastrin pentapeptide. In the proximal stomach prostaglandins have an opposite role; they promote tonic contraction. Because of the diverse effects of prostaglandins, they probably have complicated effects on gastric motility. In general, emptying of solids should be retarded by endogenous prostaglandins, whereas emptying of fluids may be facilitated by these compounds. Overproduction of prostaglandins may produce abnormal motility patterns and affect gastric emptying. A case of gastric pseudoobstruction apparently involving prostaglandins is discussed.
Effect of neurotensin on intestinal capillary permeability and blood flow
Authors: Harper S. L. , Barrowman J. A. , Kvietys P. R. , Granger D. N.
Published: December 2017

Experiments were performed in 10 cats of either sex to ascertain the effects of postprandial arterial plasma concentrations of neurotensin (NT) on intestinal capillary permeability and blood flow. NT was infused intra-arterially into an isolated perfused loop of terminal ileum to produce a 182 +/- 15 (SE) pM plasma NT concentration. Intestinal lymph (L) and plasma (P) protein concentrations were measured at various venous pressures under control conditions and during NT infusion. The osmotic reflection coefficient (sigma d) was estimated under all conditions assuming sigma d = 1 - L/P at high capillary filtration rates. NT infusion significantly (P less than 0.001) reduced sigma d to 0.73 +/- 0.02 (SE) from a control level of 0.91 +/- 0.01. NT infusion also significantly increased intestinal blood flow [47.0 +/- 4.3 (SE) ml X min-1 X 100 g-1] versus control (36.6 +/- 3.2 ml X min-1 X 100 g-1), a 28.4% increase. Intestinal vascular resistance was decreased from 3.21 +/- 0.31 to 2.42 +/- 0.28 mmHg X min X ml-1 X 100 g in the absence of a change in local mean arterial blood pressure. Pore-stripping analysis of lymph and plasma solute fractions during NT infusion at high lymph flows predicted two populations of pores, 330-A and 46-A radius, accounting for 31 and 67%, respectively, of the total transcapillary hydraulic flow. NT infusion preferentially increased large-pore radius as a means of increasing intestinal capillary permeability. The rates of small- to large-pore areas and numbers were 106:1 and 5,225:1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of 1,25-dihydroxyvitamin D3 on calcium absorption in the colon of healthy humans
Authors: Grinstead W. C. , Pak C. Y. , Krejs G. J.
Published: December 2017

Calcium absorption in patients with short bowel syndrome is significantly higher when the colon is left intact. To study calcium transport in the large bowel, we investigated whether exogenous 1,25-dihydroxyvitamin D3 [1,25(OH2)D3] can induce or enhance colonic calcium absorption in healthy subjects ingesting a normal diet. Steady-state colon perfusion studies were performed before and after 1 wk of 1,25(OH)2D3 administration (2 micrograms/day, 10 subjects). Serum 1,25-dihydroxyvitamin D concentration rose from 23.0 +/- 2.2 to 39.5 +/- 4.3 pg/ml (mean +/- SE, P less than 0.01). In the basal state the mean net movement of calcium was not significantly different from zero when a 5 mM calcium gluconate solution was perfused (100 +/- 84 mumol X h-1 X entire colon secreted-1). Vitamin D administration resulted in a significant change toward calcium absorption (106 +/- 47 mumol X h-1 X entire colon absorbed-1, P less than 0.02). 1,25(OH)2D3 had no effect on colonic magnesium, phosphate, water, and electrolyte movement. This study demonstrates that in healthy humans exogenous 1,25(OH)2D3 can change colonic calcium movement toward absorption. We suspect that similar changes in colonic calcium transport are caused by endogenous 1,25(OH)2D3 when calcium deficiency has occurred in short bowel syndrome.
Development of sensitivity to cAMP-inducing hormones in the rat stomach
Authors: Gespach C. , Cherel Y. , Rosselin G.
Published: December 2017

Development of cAMP responses to secretin, pancreatic glucagon, and histamine was measured in gastric glands of fetal (day 20), postnatal (days 1-30), and adult rats (day 65). cAMP stimulation by these hormones was already detected on day 20 of gestation. cAMP generation showed biphasic variations during the 1st days of life and at the onset of weaning (day 20). Anticipated weaning at day 14 triggered precocious maturation (efficacies) of the cAMP-generating systems sensitive to secretin, glucagon, and histamine without changing the potencies of the hormones. During development, the general characteristics (potency and pharmacological or regulatory properties) of the receptor-cAMP systems studied were comparable with those evidenced in adult rats. At days 5, 20, and 65, vasoactive intestinal peptide and the peptide having N-terminal histidine and C-terminal isoleucine amide (PHI) were about 100 times less potent than secretin (EC50 = 1.5 X 10(-9) M secretin). The histamine action could be blocked by the competitive H2-receptor antagonist cimetidine (70-100% inhibition) as well as by the noncompetitive inhibitor somatostatin (37-62% inhibition). The data indicate that these regulatory hormones (secretin, glucagon(s), histamine, and somatostatin) might have a direct effect on gastric glands and may modulate their biological activities (metabolism, differentiation, proliferation, and exocrine and endocrine secretions) from the neonatal period in rats. The important physiological role of weaning on the final maturation of the cAMP-generating systems in rat gastric glands is underlined.
Discovery of a cholecystokinin analogue with partial agonist activity
Authors: Howard J. M. , Knight M. , Jensen R. T. , Gardner J. D.
Published: December 2017

In dispersed acini from guinea pig pancreas, cholecystokinin-(27-32)-amide [CCK-(27-32)-NH2] did not stimulate amylase secretion and inhibited the stimulation caused by CCK-(26-33). In dispersed acini from mouse or rat pancreas, CCK-(27-32)-NH2 stimulated amylase secretion. The stimulation of amylase secretion caused by a maximally effective concentration of CCK-(27-32)-NH2 was less than that caused by a maximally effective concentration of cholecystokinin-(26-33), and in contrast to the action of cholecystokinin-(26-33) supramaximal concentrations of CCK-(27-32)-NH2 did not cause submaximal stimulation of amylase secretion. Dibutyryl cGMP and proglumide each inhibited the stimulation of amylase secretion caused by CCK-(27-32)-NH2. CCK-(27-32)-NH2 inhibited binding of 125I-labeled CCK to mouse and rat pancreatic acini. These results indicate that, in mouse and rat pancreatic acini, CCK-(27-32)-NH2 is a partial agonist and that this partial agonist activity is produced by occupation of the CCK receptor by CCK-(27-32)-NH2.
Mechanism of arginine protection against ammonia intoxication in the rat
Authors: Goodman M. W. , Zieve L. , Konstantinides F. N. , Cerra F. B.
Published: December 2017

To examine the beneficial effect of arginine on ammonia intoxication, rats were injected intraperitoneally with a single dose of NH4Cl (6.75 mmol/kg) with and without arginine (5.0 mmol/kg) or ornithine (5.0 mmol/kg). Arginine or ornithine reduced the blood ammonia nitrogen at 30 min after NH4Cl injection from 3,288 +/- 800 micrograms/dl (mean +/- SE) to 538 +/- 90 and 575 +/- 34 micrograms/dl, respectively. In rats administered this dose of NH4Cl, arginine or ornithine did not increase further the hepatic carbamoyl-phosphate synthetase (EC 6.3.4.16) activation by N-acetylglutamate beyond the effect of NH4Cl. However, arginine or ornithine did increase the hepatic citrulline and urea content as well as the plasma urea concentration in these NH4Cl-injected rats. In rats injected with four doses of NH4Cl (2.5 mmol/kg), arginine or ornithine pretreatment increased the urea excretion and normalized the orotic acid excretion. These results indicate that arginine mitigates ammonia intoxication in the rat by increasing ornithine carbamoyltransferase activity through increased ornithine availability and not via activation of N-acetylglutamate synthetase. By increasing ornithine carbamoyltransferase activity, ornithine enhances the conversion of ammonia to citrulline and urea.
Measurements of gastric mucosal blood flow by hydrogen gas clearance
Authors: Ashley S. W. , Cheung L. Y.
Published: December 2017

The validity of the use of H2 gas clearance to measure gastric mucosal blood flow (GMBF) was investigated in the intact stomach of anesthetized dogs. With a modified, more sensitive platinum electrode, we were able to reduce the H2 gas concentration to a nonflammable gas mixture. GMBF was repeatedly measured when the dogs inhaled gas containing 100, 10, and 3-5% H2. GMBF measured using 100% H2 demonstrated close correlation with inhaled gases containing 10% H2 (r = 0.84, slope = 0.89) and 3-5% H2 (r = 0.91, slope = 0.88). At a nonflammable concentration of 3% H2, it was safe to add 20% O2 into the gas mixture. The addition of O2 into the inhaled gas eliminated the transient hypoxia noted otherwise. It was also possible to reduce the gas flow rate from 5-10 to 1-3 l/min. Regression analysis of GMBF determined by inhalation of 5% H2 at these flow rates revealed a significant linear correlation (r = 0.95, slope = 1.13). In 10 dogs GMBF determined by using these low concentrations of H2 at the low flow rates also showed a good agreement (r = 0.93, slope = 0.65) with that measured by radioactive microspheres. These two methods also demonstrated comparable changes in GMBF induced by intravenous infusion of histamine and vasopressin. It was concluded that, with the technique as modified in our laboratory, H2 gas clearance could be a safe and accurate tool for quantitating gastric mucosal blood flow.
Stimulation of mucosal growth by a dietary amine
Authors: Dembinski A. B. , Yamaguchi T. , Johnson L. R.
Published: December 2017

Nutrients are believed to have a direct trophic effect on the cells of the gastrointestinal mucosa. However, no normal constituent of the diet has ever been shown to stimulate mucosal growth when administered orally. Sham-operated and antrectomized rats were fed 20 g of powdered commercial rat pellets daily or 20 g of food containing dimethylamine (100 mumol/g food). After 7 days rats were killed and growth of the mucosa of the oxyntic gland portion of the stomach and 2-cm segments of duodenum, jejunum, and proximal colon was determined. Antrectomy resulted in significant decreases in the weight and the DNA, RNA, and protein content of all four tissues and serum gastrin levels. Feeding amines abolished the differences in the oxyntic gland and duodenal mucosa. In general, the effect of amines decreased distally. Feeding amines did not significantly alter serum gastrin levels. These data indicate that dietary amines may directly stimulate the growth of gastrointestinal mucosa. These results may explain some of the proximal-to-distal gradients described for the growth of the mucosa.
Rat lingual lipase: partial purification, hydrolytic properties, and comparison with pancreatic lipase
Authors: Roberts I. M. , Montgomery R. K. , Carey M. C.
Published: December 2017

We have partially purified lingual lipase from the serous glands of rat tongue. With a combination of Triton X-100 extraction or Triton X-114 phase-separation techniques, Bio-Bead SM-2 treatment, dialysis, and gel filtration on Sephadex G-200 or Sephacryl S-300, we obtained a sparingly soluble lipid-free protein demonstrating hydrolytic activity against triglycerides and negligible phospholipase or cholesteryl esterase activities. Compared with homogenate, specific activities of the enzyme were enriched 3- to 5-fold prior to gel filtration and 10-fold after gel filtration. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and gel filtration under denaturing conditions (6 M guanidine X HCl or 0.1% sodium dodecyl sulfate) revealed one major glycoprotein band with Mr approximately 50,000. Gel filtration of the active enzyme in 0.1% Triton X-100 gave an Mr approximately 270,000-300,000, suggesting extensive self-aggregation. With both tributyrin and triolein, the pH optimum of the purified enzyme was 4.0 and activity extended from pH 2.0 to 8.0. In contrast to purified human pancreatic lipase, lingual lipase hydrolyzed triglyceride emulsions and mixed micelles stabilized with both short-chain (dihexanoyl) and long-chain (egg) lecithin and were inhibited only slightly (18-25%) by micellar concentrations of two common bile salts, taurodeoxycholate and taurocholate. Our results suggest that the hydrolysis of dietary fat by lingual lipase may extend from the pharynx through the esophagus and stomach and into the upper small intestine.
Characterization of cholecystokinin receptors on human gastric smooth muscle tumors
Authors: Miller L. J.
Published: December 2017

Gastric smooth muscle cells are a physiological target for the polypeptide hormone cholecystokinin (CCK). Human tumors arising from this type of cell, leiomyosarcomas, can retain their ability to express a receptor for CCK. To begin to characterize the human CCK receptor, we established a scheme for fractionation of these tumors to yield a membrane preparation enriched in enzyme markers of plasmalemma that saturably binds CCK. In competition-binding studies using 125I-CCK-8, only peptides structurally related to CCK competed for binding, with 50% of binding inhibited by 0.075 nM CCK-8, 0.9 nM CCK-8-desulfate, 0.9 nM gastrin-17, and 2.5 nM CCK tetrapeptide. Specificity of binding was demonstrated by showing that structurally unrelated peptides did not compete for binding. Association and dissociation of binding were temperature dependent. We have also performed affinity labeling studies to define the molecular properties of the CCK binding site. In these, the membranes were incubated with 125I-CCK-33, washed, cross-linked with disuccinimidyl suberate, solubilized, and electrophoretically separated on a polyacrylamide gel. Autoradiography of the dried gel revealed labeling of a major component with Mr 75,000 and minor components with Mr 53,000, Mr 100,000, Mr 120,000, and Mr greater than 200,000. Labeling was inhibited by CCK-8 in a concentration-dependent manner. This was also specific for CCK and structurally related peptides. These results demonstrate that gastric leiomyosarcomas are a very good source of a human CCK receptor and suggest that they may provide an easily cultured tissue with which this receptor can be fully characterized.
Effects of histamine and histamine receptor antagonists on ion transport in rabbit descending colon
Authors: McCabe R. D. , Smith P. L.
Published: December 2017

The effects of histamine on colonic ion transport were examined in in vitro preparations of rabbit descending colon. Serosal addition of histamine (10(-5) M) produced a transient increase in short-circuit current (Isc) and transepithelial conductance. The Isc response to histamine could be blocked by removing Cl from both bathing solutions, adding furosemide (10(-3) M) to the serosal bathing solution, adding indomethacin to the serosal and mucosal bathing solutions (10(-5) M), or removing Ca from the serosal bathing solution. In addition, the histamine-induced increase in Isc was inhibited in a dose-dependent manner by the H1-receptor antagonist diphenhydramine, with a maximal inhibition at 10(-4) M and a half-maximal inhibition at 3 X 10(-7) M. The H2-receptor antagonist cimetidine (10(-3) M) was without effect on the histamine response. Measurement of unidirectional Na, K, and Cl fluxes revealed that serosal addition of diphenhydramine (10(-3) M) reduced basal Isc due to a decrease in mucosal-to-serosal Na flux. Serosal addition of diphenhydramine (10(-3) M) also inhibited the increase in Isc produced by serosal addition of prostaglandin E1, 8-bromo-cAMP, cholera toxin, or the ionophore A23187. Measurement of unidirectional K and Cl fluxes revealed that prostaglandin E1 alone increased serosal-to-mucosal K and Cl fluxes and reduced the mucosal-to-serosal K flux, thereby increasing net K and Cl secretion. Serosal diphenhydramine (10(-3) M) abolished the changes in Cl fluxes produced by prostaglandin E1 and reduced the magnitude of the changes in K fluxes.(ABSTRACT TRUNCATED AT 250 WORDS)
Role of opiate receptors in regulation of enkephalin stimulation of active sodium and chloride absorption
Authors: Binder H. J. , Laurenson J. P. , Dobbins J. W.
Published: December 2017

The mechanism of opioid peptide stimulation of active Na and Cl absorption in rabbit ileum is not known. Since vasoactive intestinal peptide (VIP) modulation of electrolyte transport is mediated by specific membrane receptors, these experiments sought to determine whether membrane receptors for opioid peptides are present on rabbit ileal enterocytes. Although we found specific binding both of radiolabeled opioid peptides to homogenates of cerebrum and ileal myenteric plexi and of 125I-VIP to ileal enterocytes, specific binding of radiolabeled opioid peptides to either ileal enterocytes or their homogenates was not identified. In parallel studies, tetrodotoxin, an inhibitor of neurotransmission, did not alter VIP-stimulation of Cl secretion but inhibited D-Ala2-methionine-enkephalinamide-induced electrolyte absorption. These studies suggest that opioid peptide stimulation of active Na and Cl absorption is mediated by an unidentified intermediary agonist.