bluuebunny/crossref_metadata_2025 huggingface dataset:
Intestinal absorption of calcium: role of dietary phosphate and vitamin D
Authors: Brautbar N. , Levine B. S. , Walling M. W. , Coburn J. W.
Published: December 2017

The intestinal absorption of calcium (Ca) has been shown to depend on vitamin D3, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], and dietary phosphorus (P) concentration. This study was designed to evaluate the role of dietary P independent of vitamin D3 or 1,25(OH)2D3. Vitamin D-deficient rats were studied during dietary P restriction and were compared with control groups raised on a normal-phosphorus diet (NP). Balance studies were sued. Net intestinal Ca absorption was significantly lower with dietary P restriction compared with the NP group. This malabsorption of Ca was corrected by the administration of either D3 for 1,25(OH)2D3, despite hypophosphatemia. Everted gut sacs showed a marked reduction in the uptake of 45Ca in the duodenum, jejunum, and ileum during dietary P restriction. We concluded that dietary P concentration plays a major role in intestinal Ca absorption in the vitamin D-deficient rats. These findings suggest an effect of the low-phosphate diet on the vitamin D-dependent, Ca-transport mechanism.
Digestive end products mobilize secretory proteins from subcellular stores in the pancreas
Authors: Grendell J. H. , Rothman S. S.
Published: December 2017

Two digestive end products, D-glucose and L-lysine, produced substantial concentration-dependent release of amylase and trypsinogen, respectively, from subcellular storage pools into a postmicrosomal supernatant fraction of rat pancreatic tissue homogenate. This process was selective in that D-glucose did not lead to trypsinogen release, while L-lysine did not effect amylase. An analogue of D-glucose, 2-deoxy-D-glucose, was much less potent than D-glucose on an equimolar basis. Half-maximal release for both end-product enzyme pairs occurred at concentrations within the range of normal plasma values for these end products in the rat. Although amylase release reached an apparent plateau when the concentration of glucose was increased beyond the maximally effective level, lysine concentrations higher than that maximally effective resulted in a fall in trypsinogen release that ultimately returned (at 3.0 mM L-lysine) to the level seen in its absence. When isolated zymogen granules were exposed to the same concentrations of D-glucose or L-lysine, a similar pattern of release was seen, indicating that the zymogen granules are a source of the enzymes released from the particulate phase of the homogenates. These findings can be explained most simply by the selective movement of digestive enzymes across zymogen granule membranes in response to the presence of appropriate end products. They are also consistent with the concept that digestive end products can act rapidly and directly on the pancreatic acinar cell to regulate the mixture of enzymes secreted in response to the specific hydrolytic needs of a meal.
Autoregulation of gastric blood flow and oxygen uptake
Authors: Holm-Rutili L. , Perry M. A. , Granger D. N.
Published: December 2017

The purpose of this study was to determine whether the ability of the stomach to autoregulate blood flow and oxygen uptake is altered by sympathetic denervation. Blood flow, oxygen extraction, local arterial pressure, and venous pressure were continuously monitored in sympathetically innervated and denervated autoperfused dog stomach preparations. As perfusion pressure was reduced in increments from 120 to 20 mmHg in innervated preparations, blood flow and oxygen uptake decreased while oxygen extraction and vascular resistance increased. Reductions in perfusion pressure in denervated preparations resulted in a decrease in blood flow, oxygen uptake, and vascular resistance, whereas oxygen extraction increased. The ability of the stomach to regulate blood flow and oxygen uptake was significantly improved after denervation, i.e., vascular resistance decreased and oxygen uptake remained relatively constant when arterial pressure was reduced. Oxygen uptake in denervated stomachs was generally higher than that in innervated stomachs. Autoregulation of gastric blood flow therefore appears to be improved by denervation. The better autoregulation observed after denervation may result either from a reduction in sympathetic tone and/or the increase in gastric oxygen demand.
Blood-brain transport of tryptophan and phenylalanine: effect of portacaval shunt in dogs
Authors: Huet P. M. , Pomier-Layrargues G. , Duguay L. , du Souich P.
Published: December 2017

The blood-brain uptake process for tryptophan and phenylalanine was investigated using the multiple-indicator dilution technique in 13 unanesthetized dogs with and without portacaval shunts. Tracer doses of labeled albumin (extracellular reference) and tryptophan or phenylalanine, prepared in autologous dog plasma, were injected into one carotid artery, and dorsal sagittal sinus dilution curves were obtained. Portacaval shunting was not associated with significant changes in the initial brain uptake ratio U for tryptophan or phenylalanine, despite increases in plasma phenylalanine and tyrosine. In the 13 dogs, U was not significantly correlated with the plasma levels of either the different branched-chain or aromatic amino acids or the molar ratio between these groups. These findings do not support the current hypothesis that the active transport of aromatic amino acids across the blood-brain barrier is increased after portacaval shunt. Our data suggest, instead, that the blood-brain uptake process for aromatic amino acids is linear and increases in shunted animals because their plasma levels are increased.
Endocrine secretion of alpha-amylase by the pancreas
Authors: Miyasaka K. , Rothman S. S.
Published: December 2017

The effect of the gastrointestinal hormone, cholecystokinin-pancreozymin (CCK-PZ), on the flux of alpha-amylase across the basolateral surface of the pancreas into interstitial fluid was measured by following its appearance in the medium bathing whole rabbit pancreas in organ culture. CCK-PZ increased the rate of amylase release by about an order of magnitude for the maximum applied dose. The response was only observed at concentrations of CCK-PZ that were supramaximal for ductal enzyme secretion (320 pmol/l to 10 nmol/l). Over this range, amylase secretion into the bath varied widely with dose, whereas that into the duct remained relatively unchanged. These observations, in conjunction with others, suggest that the acinar cell, and not the duct system, is the direct source of this amylase and that there is a natural secretion of digestive enzyme from the acinar cell in the endocrine direction that is augmented by CCK-PZ or a homologous peptide.
Postnatal development: coordination of feeding, digestion, and metabolism
Authors: Henning S. J.
Published: December 2017

The rat is immature at birth and undergoes major developmental changes at the end of the suckling period. This review deals with the maturation of ingestive behavior, gastrointestinal digestive and absorptive functions, liver metabolism, and brain structure and function. Each aspect of development is physiologically correlated with the dietary transition of weaning. However, it is unlikely that the process of weaning acts as a cue for the ontogenic changes. In contrast, there is strong evidence for an important role of both thyroxine and corticosterone as coordinators of maturational events in various organ systems.
Ontogeny of tissue and serum gastrin concentrations in fetal and neonatal sheep
Authors: Lichtenberger L. M. , Crandell S. S. , Palma P. A. , Morriss F. H.
Published: December 2017

We investigated the perinatal ontogenic changes in ovine serum and tissue gastrin concentration. Fetal and maternal serum gastrin levels in serums obtained from indwelling catheters in the fetal and maternal circulations and tissue gastrin levels were assessed by radioimmunoassay and immunohistochemistry. Fetal serum gastrin concentration was undetectable until the 107th day of gestation and significantly increased to levels surpassing maternal values. Neonatal serum hormone concentration continued to rise, reaching a peak during the 4th postnatal wk and decreasing after the 4th wk coincident with weaning. Maternal serum gastrin concentration did not vary during pregnancy and did not correlate with fetal serum gastrin levels. Fetal abomasal and duodenal gastrin concentrations and abomasal G-cell number increased in parallel with the developmental alterations in fetal serum hormone levels during gestation. The developmental increase in abomasal gastrin concentration was not associated with a shift in the molecular form of the hormone. These findings support the hypothesis that circulating gastrin in the fetus is of fetal origin.
Antisecretory effects of berberine in rat ileum
Authors: Tai Y. H. , Feser J. F. , Marnane W. G. , Desjeux J. F.
Published: December 2017

The in vitro antisecretory effects of the alkaloid berberine (1.0 mM) on intestinal ion secretion and mucosal adenylate cyclase and Na-K-ATPase activities were studied in the rat ileum. Mucosal berberine did not alter the individual basal net ion fluxes and basal adenylate cyclase activity but decreased short-circuit current (Isc) and increased the net absorption of chloride plus bicarbonate. In the cholera toxin-treated tissue, mucosal berberine stimulated absorption of Na and Cl and inhibited the increased adenylate cyclase activity but did not change the specific Na-K-ATPase activity, whereas serosal berberine stimulated Na secretion and decreased Isc. Mucosal berberine also decreased Isc, increased Cl permeability, and reversed the ion secretion induced by dibutyryl cyclic AMP, the heat-stable enterotoxin of Escherichia coli, and methylprednisolone administration. The antisecretory effects of mucosal berberine may be explained by stimulation of a Na-Cl-coupled absorptive transport process. The mechanism of action of serosal berberine remains to be elucidated. However, it is clear that mucosal berberine affects intestinal ion transport by mechanisms different from stimulation of the Na pump and probably at a step distal to the production or degradation of cyclic AMP or cyclic GMP.
Uptake of cholesterol into rabbit jejunum using three in vitro techniques: importance of bile acid micelles and unstirred layer resistance
Authors: Thomson A. B. , O'Brien B. D.
Published: December 2017

The rate of uptake (Jd) of cholesterol into the intestine is influenced by the effective resistance of the unstirred water layer, the concentration of the probe molecule at the aqueous-membrane interface, and the passive permeability characteristics of the membrane. This study was undertaken to determine the influence of the bile acid micelle and the unstirred water layer on the Jd of cholesterol into rabbit jejunum, using everted sacs, full-thickness biopsies, and disks. When the bulk phase was stirred and the resistance of the unstirred layer was low, there was a linear relation between cholesterol concentration in the bulk phase and Jd when the concentration of taurodeoxycholic acid (TDC) was constant, but increasing TDC in the presence of a constant concentration of cholesterol was associated with a decline in Jd. When the concentration of both TDC and cholesterol was varied but the ratio of TDC to cholesterol was maintained constant, Jd increased slightly. The Jd of cholesterol was higher into sacs than into biopsies, which in turn was greater than into disks; Jd into disks was much lower when the resistance of the unstirred layer was high. These results suggest that 1) the bile acid micelle serves to provide a reservoir for partitioning of the cholesterol from the micelle into the aqueous phase from which the cholesterol is absorbed; 2) the Jd of cholesterol into disks of jejunum is influenced by the effective resistance of the unstirred water layer; and 3) although the quantity of cholesterol Jd varies markedly between sacs, biopsies, and disks, the qualitative aspects of the role of the bile acid micelle in cholesterol absorption were similar using the different in vitro techniques.
Gastrointestinal tract O2 uptake and regional blood flows during digestion in conscious newborn lambs
Authors: Eldelstone D. I. , Holzman I. R.
Published: December 2017

We determined gastrointestinal tract O2 uptake, cardiac output, regional blood flows, and whole-body O2 uptake before and for 1-6 h after feeding in 10 chronically catheterized unanesthetized lambs (9-15 days of age). Total gastrointestinal blood flow (sum of blood flows to the stomach, small intestine, and colon, as calculated with the radioactive microsphere technique) increased 23% at 1 h postprandially. This increased flow at 1 h was due to a large increase in blood flow to the stomach, whereas blood flows to the small intestine and colon did not change significantly. By 2 h, stomach blood flow and thus total gastrointestinal blood flow had returned to fasting values. In contrast, total O2 uptake by the gastrointestinal tract organs (stomach, small intestine, and colon) increased 65% at 1 h, 51% at 2 h, and 28% at 3 h postprandially in association with increases in O2 extraction (O2 uptake/O2 delivery) of 41% at 1 h, 45% at 2 h, and 27% at 3 h. There were no digestion-related changes in whole-body O2 uptake or in cardiac output and its distribution to the brain, heart, kidney, liver (hepatic artery), and carcass. Our data indicate that postprandial increases in O2 demand by gastrointestinal tract organs of the newborn animal are met primarily by enhanced tissue O2 extraction, rather than by metabolic hyperemia, because the postprandial hyperemia observed in the neonate is of short duration and is confined to the stomach.
Effects of spironolactone and amiloride on corticosteroid-induced changes in colonic function
Authors: Charney A. N. , Wallach J. , Ceccarelli S. , Donowitz M. , Costenbader C. L.
Published: December 2017

Mineralocorticoid and glucocorticoid effects on colonic electrolyte absorption were compared by examining the alterations caused by spironolactone and amiloride in corticosteroid-treated rats. Animals were treated for 3 days with deoxycorticosterone acetate (DOCA; 0.5 mg . 100 g-1 . day-1), methylprednisolone (MP; 3 or 0.5 mg . 100 g-1 . day), and spironolactone (14 mg . 100 g-1 . day-1 im) singly or in combination. On day 4, rats were anesthetized with pentobarbital sodium and perfused in vivo with Ringer-HCO3 solution. Both doses of MP and DOCA increased net colonic sodium and water absorption and mucosal Na-K-ATPase activity. Concurrent spironolactone treatment completely prevented these effects in DOCA-treated rats but had no effect in MP-treated rats. Untreated, MP-treated, and DOCA-treated animals were perfused with a Ringer-HCO3 solution containing 1 mM amiloride. Amiloride reduced net colonic sodium and water absorption, transmural potential difference, and potassium secretion in all rats by approximately 55%. These effects were almost immediate and completely reversible. These findings in the rat suggest that 1) different receptors mediate the colonic effects of mineralocorticoids and glucocorticoids and 2) these corticosteroids do not differ in their relative effects on amiloride-sensitive and amiloride-resistant colonic sodium transport processes.
Transport of calcium by duodenum of spontaneously hypertensive rat
Authors: Toraason M. A. , Wright G. L.
Published: December 2017

The absorption of calcium by segments of duodenum obtained from spontaneously hypertensive (SH) rats and normotensive Wistar-Kyoto (WKy) rats was measured before and after the development of hypertension. The systolic blood pressure (SBP) of 5-wk-old SH rats (116 +/- 4 Torr) was significantly elevated above that of age-matched WKy rats (103 +/- 3 Torr) but was not at a level generally considered to be hypertensive. Values obtained for calcium transport [ratio of serosal-to-mucosal fluid 45Ca2+ concn (S/M ratio)] from everted duodenal sacs were similar between the two groups at this age. At 12 wk of age, SH rats exhibited a SBP (153 +/- 4 Torr) well above that of WKy controls (127 +/- 3 Torr), and calcium S/M ratios for duodenal sacs were significantly greater than the WKy control values. Similarly, the in vivo uptake of calcium in duodenal segments was significantly elevated in 12-wk-old SH rats compared with WKy controls. The administration of vitamin D3 or its metabolite, 25-hydroxycholecalciferol, had no detectable effect on duodenal transport of calcium in 12-wk-old SH or WKy rats. By comparison, 1,25-dihydroxycholecalciferol produced a significant increase in duodenal calcium transport both in vitro and in vivo in WKy but not in SH rats. The results indicate a distinct abnormality in the transport of calcium in the duodenum of SH rats, suggesting that the decrease in duodenal uptake of calcium that normally occurs with maturation is slow to develop in this rat strain.
Bicarbonate absorption by in vitro amphibian small intestine
Authors: White J. F. , Imon M. A.
Published: December 2017

Isolated segments of jejunum from Amphiuma bathed in Cl--free (SO42(-)) media usually generated serosa-negative electrical potentials when HCO3(-) was present in the media. Bidirectional isotope fluxes under short circuit revealed a negligible absorption of Na+ and a residual flux consistent with anion absorption. Acetazolamide (10(-4) M) eliminated the short-circuit current and the residual flux. Segments of jejunum exposed on the mucosal surface to HCO3(-) (pH 7.4) alkalinized the unbuffered serosal fluid at a rate of about 1.1 mueq . h-1 . cm-2, as measured by the pH-stat while clamped at zero transepithelial potential. Acetazolamide, anoxia, and 2,4-dinitrophenol lowered the rate of alkalinization and simultaneously reduced the short-circuit current by an equal amount. Absorption was constant above a [HCO3(-)] of 35 meq/l and uninfluenced by applied transepithelial voltage gradients. HCO3(-) absorption was not reduced after replacement of media Na+ or Cl- but was reduced on addition of ouabain or removal of K+. It is concluded that the jejunum actively absorbs HCO3(-) by an electrogenic process that does not involve Na+-H+ exchange.
Cation effects on acid secretion in rabbit gastric glands
Authors: Koelz H. R. , Sachs G. , Berglindh T.
Published: December 2017

The ability of isolated gastric glands to produce acid as a function of intra- and extracellular concentrations of K+ and Na+ was investigated. Ouabain inhibited acid formation as measured by the aminopyrine (AP) accumulation technique in a dose-dependent manner with an ED50 of 2 X 10(-6) M at 5.4 mM extracellular K+. This inhibition was counteracted by increasing extracellular K+ or decreasing extracellular Na+. In K+-free solutions with regular Na+, the AP accumulation was almost totally abolished; the readdition of K+ rapidly restored the response with a K0.5 of 1 mM extracellular K+. In the absence of Na+, with or without ouabain, there was always a significant residual AP accumulation, but the K0.5 of extracellular K+ required for acid formation increased to about 20 mM. Despite repeated washings in Na+-K+-free solutions, the intracellular K+ content could not be decreased below 24 mM above the apparent K0.5 for K+. It was found that the intracellular K+ could be depleted without disturbance of the acid secretory function if the glands were treated with the neutral ionophore amphotericin B and ouabain in K+-Na+-free solutions. Complete dose-response curves of H+ secretion as a function of K+ concentration could now be obtained. Thus the K0.5 for K+ activation of AP accumulation was 16.5 +/- 0.9 mM; upon histamine stimulation of the glands, the K0.5 decreased to 10.4 +/- 0.7 mM. Intracellular K+ concentrations above approximately 60 mM inhibited AP accumulation. Na+ dose dependently inhibited the K+-induced response. At low extracellular K+ concentrations, a ouabain-insensitive K+ accumulation mechanism was unmasked. This K+ uptake was partly inhibited y p-chloromercuribenzene sulfonic acid and by inhibitors of the gastric H+-K+-ATPase and amplified by inhibitors of K+ conductance channels such as Ba2+. The K+ content of gastric glands is mainly regulated by the Na+-K+-ATPase, but additional K+-uptake pathways are present. The affinity for K+ is increased in histamine-stimulated glands, which might indicate one mechanism of stimulating the secretory response. Na+ inhibits secretion possibly by binding to the cytosolic cation site of the gastric ATPase. The cation relationship to acid secretion in the rabbit parietal cell is similar to that described for vesicles isolated from hog gastric mucosa.
Intestinal secretion of mucin in chronically reserpine-treated rats
Authors: Forstner J. , Maxwell B. , Roomi N.
Published: December 2017

Intestinal glycoprotein synthesis and secretion were measured in vivo and in vitro in rats treated for 7 days with reserpine. Goblet cell mucin was measured by radioimmunoassay. Reserpine-treated rats contained 1.4 times more mucin in intestinal tissue than control rats (P less than 0.05) and incorporated [1-14C]glucosamine in vivo at 1.52 times the rate of controls (P less than 0.01). Intestinal slices incubated for 90 min in vivo incorporated 1.4 times more [14C]glucosamine (P less than 0.001) and 3.0 times more [3H]threonine (P less than 0.01) into protein of reserpine-treated tissue than controls. The extra 14C was localized to mucin and to smaller components that had affinity for Concanavalin-A-Sepharose, did not bind to mucin antibody, and were therefore nonmucin glycopeptides. In vitro secretion of mucin was three times greater for reserpine-treated tissue than for control tissue (P less than 0.0001). There was an impairment in the mucin secretory response of reserpine-treated tissue to the addition of cholera toxin. Thus, chronic reserpine treatment results primarily in a generalized increase in the rate of intestinal glycoprotein synthesis, subsequent accumulation in tissues, and an increased (but not fully proportional) secretion of mucin. We speculate that in cystic fibrosis a similar sequence of glycoprotein abnormalities may be responsible for the gradual obliteration of exocrine gland ducts with viscous mucus.
Postprandial intestinal hyperemia: role of bile salts in the ileum
Authors: Kvietys P. R. , McLendon J. M. , Granger D. N.
Published: December 2017

In an autoperfused dog ileum preparation, artificial pressure, venous outflow pressure, blood flow, and arteriovenous oxygen difference were measured while bile and bile salt solutions, at physiological concentrations, were placed in the lumen. Intraluminal placement of endogenous bile, synthetic bile, or bile salt solutions increased ileal blood flow (99 +/- 10, 94 +/- 20, and 104 +/- 17%, respectively) and oxygen uptake (30 +/- 5, 36 +/- 9, and 28 +/- 5%, respectively). Endogenous bile pretreated with cholestyramine, a bile salt-sequestering resin, did not alter ileal blood flow, yet increased ileal oxygen uptake by 11 +/- 3%, a response similar to that observed while Tyrode's solution (the vehicle) was in the lumen. Intra-arterial infusion of bile salts increased ileal blood flow in a dose-dependent manner, while not significantly altering ileal oxygen uptake. The results of the present study indicate that bile salts play an important role in the functional (postprandial) hyperemia in the ileum by 1) directly dilating the ileal vasculature and 2) enhancing ileal metabolism during their active absorption.
Acute inhibition of intestinal lipid transport by Pluronic L-81 in the rat
Authors: Tso P. , Balint J. A. , Bishop M. B. , Rodgers J. B.
Published: December 2017

Lymph fistula rats were used to determine the acute effects of the hydrophobic surfactant, Pluronic L-81, on lipid transport by the small bowel. Animals were infused intraduodenally with a lipid emulsion containing [3H]triolein and Pluronic L-81, and the rate of intestinal transport of absorbed lipid into lymph was studied using liquid scintillation spectrometry. With this technique, various dose levels of Pluronic L-81 were analyzed for a possible inhibitory effect on lipid transport. Also, the rate at which this agent produced inhibition of intestinal lipid transport was determined. Results were correlated with electron microscopic studies of jejunal enterocytes and lipoprotein particles recovered in intestinal lymph. Infusion of Pluronic L-81 at a rate of 0.25 mg/h had no effect, but infusion at 0.5 and 1 mg/h produced a dramatic reduction in lipid transport by the small bowel. The rate of inhibition of lymphatic lipid output was rapid, with a t1/2 of 69 min for the 0.5 mg/h dose and 35 min for the 1 mg/h dose. This inhibition of lipid transport was associated with marked mucosal accumulation of lipid as demonstrated by radiochemical and morphological data. By electron microscopic analysis, only very low-density lipoprotein-sized particles were transported into lymph by enterocytes exposed to an effective dose of Pluronic L-81. It is concluded that small amounts of Pluronic L-81 produce a striking inhibition in the intracellular transport of chylomicron-sized particles, thereby blocking secretion of chylomicrons by the enterocytes. Furthermore, this action is very rapidly produced by effective doses of this agent.
A villous cell-derived inhibitor of intestinal cell proliferation
Authors: May R. J. , Quaroni A. , Kirsch K. , Isselbacher K. J.
Published: December 2017

To test the hypothesis that the intestinal villous cell synthesizes a mitotic inhibitor that is specific for crypt cells, we have partially purified an extract from rat intestinal villous cells (VCE) and have demonstrated that it strongly and reversibly inhibits cell division and DNA synthesis in an intestinal epithelial cell line (IEC-6 cells). VCE produced a 60--70% inhibition of [3H]thymidine incorporation into DNA and a similar magnitude of inhibition of labeling of nuclei in autoradiographic studies. This inhibition was not associated with cytotoxicity as assessed by the effect of VCE on 51Cr release, hexose or amino acid uptake, and protein synthesis. VCE appears specific for IEC-6 cells because it did not affect DNA synthesis in 10 other cell lines, and extracts derived from other cell lines and from colonic mucosa did not affect DNA synthesis in IEC-6 cells. VCE may represent a villous cell factor involved in the control of intestinal epithelial cell turnover in vivo.
Effects of individual taurine-conjugated bile acids on biliary lipid secretion and sucrose clearance in the unanesthetized dog
Authors: Gilmore I. T. , Barnhart J. L. , Hofmann A. F. , Erlinger S.
Published: December 2017

The effect of three taurine-conjugated bile acids on bile flow, induced biliary secretion of phospholipids and cholesterol, and the hepatobiliary clearance from plasma of sucrose and erythritol (two uncharged, nonmetabolizable permeability probe molecules) was assessed in the unanesthetized bile fistula dog under steady-state conditions. Synthetically prepared chenodeoxycholyltaurine, cholytaurine, or urological rate for randomized 90-min periods, and four 10-min samples of bile were taken at the end of each period. Induced bile flow (per mumoles of bile acid) was calculated to be about one-third higher with ursodeoxycholyltaurine than with the other bile acids. Induced phospholipid secretion was identical for all bile acids, but cholesterol secretion differed: the two dihydroxy taurine conjugates induced considerably more cholesterol per molecule bile acid or phospholipid than colyltaurine. Further, ursodeoxycholyltaurine induced significantly more cholesterol secretion than chenodeoxycholyltaurine. Erythritol clearances were identical for all bile acids, and sucrose clearance, although slightly higher for chenodeoxycholyltaurine than ursodeoxycholyltaurine, was similar for all three conjugated bile acids. The results indicate that, for these two 3,7-dihydroxy bile acids, the orientation of the 7-hydroxyl group on the steroid nucleus has a marked influence on cholesterol secretion into bile and bile flow but not on the apparent permeability of the hepatobiliary tree.
cAMP and calcium in generation of slow waves in cat colon
Authors: Anuras S.
Published: December 2017

Rhythmic oscillations in interactions between cAMP and calcium have been proposed to account for a variety of rhythmic phenomena in cells. This idea was investigated in relation to the rhythmic signals (electrical slow waves) found in the electromyogram of the cat colon. A longitudinal strip of muscularis propria from cat colon was studied in a superfusion bath that allowed recording of the electromyogram from eight sites that were 2 cm apart. The effect of increasing cAMP (by exposure of the tissue to cAMP, dibutyryl cAMP, isobutylmethylxanthine, theophylline, caffeine, and papaverine) was to reduce frequency and amplitude of slow waves and duration of migrating spike bursts. All these maneuvers raised tissue cAMP levels. Dibutyryl cGMP and cGMP had no effect. THe changes in slow waves, but not migrating spike bursts, seen with raised cAMP levels were partly reversed by raising the calcium concentration in the extracellular fluid. Raising the extracellular sodium and potassium concentrations had no effect. The results are consistent with the hypothesis that interactions between cAMP and calcium are involved in slow-wave generation in colon muscle.
Gastric mucosal cell proliferation during development in rats and effects of pentagastrin
Authors: Majumdar A. P. , Johnson L. R.
Published: December 2017

Changes in cell proliferation and cell loss in the gastric mucosa were examined during the first 4 wk of life. The effect of pentagastrin on these parameters before and after weaning was also investigated. The results revealed that DNA content of mucosa and lumen increased with age. However, when luminal DNA (an assessment of cell loss) content was expressed as percent of total mucosal DNA (referred to as percent cell loss), an inverse relationship with age was observed. The rate of mucosal DNA synthesis, measured in vitro, was found to remain elevated up to the age of 15 days and then dropped dramatically within the next 5--6 days after which it decreased slowly. The rate of mucosal DNA synthesis in 5- to 15-day-old rats was found to be 10--15 times higher than in 20- to 30-day-old rats. In 10-day-old suckling young, mucosal thymidine kinase activity was also found to be higher than in 20- to 28-day-old rats. On the other hand, total incorporation of [3H]thymidine into mucosal DNA per stomach was found to be significantly greater in 21- to 28-day-old weaned rats than in the 10-day-old suckling young. Multiple injections of pentagastrin to 28-day-old rats significantly increased mucosal DNA synthesis and thymidine kinase activity by 43 and 200%, respectively, and cell loss by 30% when compared with the saline control. The hormone did not affect DNA synthesis, thymidine kinase, or cell loss in 10-day-old rats. There were considerable increases in 20-day-old rats that were not statistically significant due to the variation of the data.
Characterization of isolated epithelial cells from rat small intestine
Authors: Hartmann F. , Owen R. , Bissell D. M.
Published: December 2017

Intestinal mucosal cells from the rat have been isolated by a new technique involving intravascular perfusion of an intestinal segment with collagenase. Detached cells were flushed from the intestinal lumen with a second perfusion circuit containing an oxygenated buffered solution with 1% bovine serum. Sequential collection of cells at intervals during the period of perfusion revealed that villus-tip cells are recovered first (after 15 min of collagenase perfusion), followed by midvillus (after 25 min) and lower villus cells (after 35 min). The isolated cells were judged intact and viable by the criteria of trypan blue dye exclusion, ultrastructural appearance, and metabolic activity. They were characterized as villus-tip, midvillus, and lower villus-crypt cells by their alkaline phosphatase and sucrase activity, glycoprotein formation, and [3H]thymidine incorporation. Microsomal monooxygenase activity was four to five times greater in villus-tip than in lower villus cells, whereas heme oxygenase exhibited a reverse gradient. The isolated cells synthesized heme and bilirubin under cell culture conditions.
Splanchnic hemodynamics in portal-hypertensive rats: measurement with gamma-labeled microspheres
Authors: Groszmann R. J. , Vorobioff J. , Riley E.
Published: December 2017

A method to quantitate hepatic arterial flow (HA), portal venous flow (PBF), and blood flow through portal-systemic shunts (ShBF) in portal-hypertensive rats is described. This method relies on the injection of two differently radiolabeled microspheres (15 micrometers) into the left ventricle and spleen. To evaluate the usefulness of this technique, studies were performed on normal, cirrhotic, and portal vein-ligated rats anesthetized with ketamine. With this method, PBF is calculated indirectly from the sums of the blood flow of the splanchnic organs that drain into the portal vein. In the portal-hypertensive animals with portal-systemic shunting, this technique allows for the determination of PBF perfusing the liver [hepatic fraction of portal flow (HFP)] and PBF escaping through portal-systemic shunts (ShBF). The portal vein-ligated rats have higher HA flow (0.68 +/- 0.08 ml . min-1 . g-1) and lower HFP (0.08 +/- 0.01 ml . min-1 . g-1) than either the cirrhotic (HA: 0.27 +/- 0.03 ml . min-1 . g-1, P less than 0.01; HFP: 1.20 +/- 0.20 ml . min-1 . g-1, P less than 0.01) or the normal rat (HA: 0.29 +/- 0.06 ml . min-1 . g-1, P less than 0.01; HFP: 1.39 +/- 0.16 ml . min-1 . g-1, P less than 0.01). No significant difference was found between the cirrhotic and normal rats. The ShBF was higher in the portal vein-ligated rats (21.4 +/- 2.8 ml/min) than in the cirrhotic (4.6 +/- 2.5 ml/min, P less than 0.001) or normal rats (0.03 +/- 0.005 ml/min, P less than 0.01). The difference between the cirrhotic and normal animals was also significant (P less than 0.05). This is a simple, rapid, and reliable technique that allows for the quantitation of splanchnic hemodynamics in experimental models with portal hypertension.
Intestinal phospholipase A and triglyceride lipase: localization and effect of fasting
Authors: Shakir K. M. , Gabriel L. , Sundaram S. G. , Margolis S.
Published: December 2017

We investigated the distribution of phospholipase A and triglyceride lipase in the rat small intestine and the effects of heparin and hormones on enzyme release. Phospholipase A activity was 10 times higher in the ileum than in the jejunum; triglyceride lipase activity was threefold higher in the jejunum than in the ileum. Activities of both enzymes were much greater in villus than in crypt cells. The specific activity of phospholipase A was highest in microsomes and least in cytosol. The crude nuclei and brush-border fraction contained 40.5% of total phospholipase A activity; mitochondria contained 33.8%; and microsomes, 17.4%. Phospholipase A activity increased significantly in the distal intestinal mucosa in fasted rats compared with controls. Heparin did not increase the release of phospholipase A by isolated intestinal cells or perfused intestinal vasculature. Thus, the small intestine probably does not contribute significantly to the phospholipase A activity of postheparin plasma. Hormones and cAMP, which inhibit the secretion of phospholipase A and triglyceride lipase from isolated hepatocytes, had no effect on the release of either enzyme from intestinal cells.
Plasma pancreatic trypsinogens in chronic renal failure and after nephrectomy
Authors: Geokas M. C. , Reidelberger R. , O'Rourke M. , Passaro E. , Largman C.
Published: December 2017

The kidney has previously been shown to be a major site for the plasma clearance of pancreatic trypsinogens in the rat. This study investigated plasma concentrations of anionic and cationic trypsinogen in chronic renal failure and anephric patients. Plasma concentrations were significantly elevated in both groups of patients. Hemodialysis did not change their plasma levels. The plasma levels of anionic and cationic trypsinogens were highly correlated in patients and normal subjects; however, the relative concentrations of anionic trypsinogen were significantly higher in renal failure patients. This suggests that in patients with renal failure the secondary clearance mechanisms for these plasma proteins more efficiently clear cationic molecules. In normal dogs, intravenous infusion of synthetic octapeptide of cholecystokinin (CCK-8) resulted in small transitory increases in plasma trypsinogen levels. After nephrectomy, basal levels of anionic and cationic trypsinogen were elevated, and intravenous infusion of CCK-8 resulted in prolonged, high levels of plasma trypsinogens.
Coordinate loss of glucocorticoid responsiveness by intestinal enzymes during postnatal development
Authors: Henning S. J. , Leeper L. L.
Published: December 2017

Jejunal sucrase is known to display glucocorticoid responsiveness from birth through day 17 but not beyond that age. The aim of the current study was to determine whether this abrupt loss of responsiveness was shared by maltase, lactase, and acid beta-galactosidase. Glucocorticoid concentrations were manipulated by both adrenalectomy (ADX) and by administration of cortisone acetate (CA). Surgery or treatment was performed on each day from 16--22 days of age. Maltase activity was reduced by ADX at day 18 and earlier and was increased by CA at days 16 and 17. There were no effects at later ages. Acid beta-galactosidase was increased by ADX only at day 18 and earlier and was decreased by CA only at day 16. Lactase activity was increased by ADX at all ages up to and including day 20 but was reduced by CA only at days 16 and 17. Thus, we conclude that loss of glucocorticoid responsiveness at a relatively early stage of development is a common feature of both brush-border and lysosomal enzymes of the small intestine.
Ethyl alcohol interferes with excitation-contraction mechanisms of canine antral muscle
Authors: Sanders K. M. , Bauer A. J.
Published: December 2017

Ethyl alcohol (EtOH) inhibited spontaneous and acetylcholine (ACh)-induced contractions in a dose-dependent manner (0.1-2.5%). These concentrations also reduce the amplitudes of intracellularly recorded slow waves. The effects of EtOH do not appear to be mediated by adrenergic or prostaglandin mechanisms, nor can they be explained on the basis of hyperosmolarity. At higher concentrations (1-10%), EtOH totally abolished phasic contractile activity and caused tonic contraction. ACh was not able to restore normal phasic contractions to muscles treated with EtOH above 2.5% and, in fact, further enhanced the force of the tonic contraction. The membrane potential response to EtOH above 1% was biphasic; the membrane transiently hyperpolarized and then tonically depolarized. It appears that many of the effects of EtOH on gastric emptying might be due to direct interference by EtOH in the membrane events leading to excitation-contraction coupling in gastric smooth muscle.
Oxygen uptake and mechanical tension in esophageal smooth muscle from opossums and cats
Authors: Schulze-Delrieu K. , Crane S. A.
Published: December 2017

In 44 opossums and 4 cats weighing 1.5-2.5 kg, measurements of O2 consumption were made on esophageal muscle strips using a modified Clark-type polarograph. All strips were cut in the transverse axis of the esophagus and comprised the circular and longitudinal muscle layers and intrinsic nerves. Strips were 20 mm long, 2 mm wide, and less than 0.5 mm thick. The average uptake by all strips was less than 5 microliters O2 . mg dry muscle-1.h-1 at 37 degrees C and was temperature dependent (Q10, 2.2). There was no difference in base-line O2 consumption between strips coming from the proximal, middle, or distal third of the esophageal body and strips coming from the lower esophageal sphincter. Increases in length or tension increased the O2 consumption by sphincter strips but had no effect on body strips. Carbachol (10(-5) M) led to increases of base-line muscle tension and O2 consumption in both sphincter and body strips. Isoproterenol (10(-6) M) decreased the baseline tension and O2 consumption in sphincter strips only. The maintenance of a high basal tension by the lower esophageal sphincter is oxygen dependent and therefore an active muscular process. Also, no gradient of metabolic activity can be demonstrated along the smooth muscle segment of the esophagus.
Hepatic stimulator substance: physicochemical characteristics and specificity
Authors: LaBrecque D. R. , Bachur N. R.
Published: December 2017

This laboratory has reported previously that a cytoplasmic extract of weanling or regenerating adult rat liver (but not normal rat liver) will produce a 2.5-fold increase in the incorporation of tritiated thymidine ([3H]dThd) into liver DNA of a 34%-hepatectomized test animal. (J. Physiol. London 248: 273-284, 1975). The present study showed that hepatic stimulator substance (HSS) will stimulate DNA synthesis in normal adult rats and CF1 mice as well. The increased incorporation of [3H]dThd into DNA produced in the normal, nonhepatectomized adult rat was comparable with that induced by a 34% hepatectomy. Autoradiographic studies revealed that the [3H]dThd was incorporated into nuclear DNA and that the stimulation occurred almost exclusively in parenchymal cells. HSS was shown to be heat stable (100 degrees C for 15 min) and was precipitated but not inactivated by alcohol. Ultrafiltration and dialysis studies suggested a molecular weight slightly greater than 10,000. HSS proved to be organ specific, stimulating the liver but not the kidney, bone marrow, or spleen. HSS was found to contain no insulin, glucagon, epidermal growth factor, or peptides of the nonsuppressible insulinlike/multiplication-stimulating activity (somatomedin) group.
Hemodynamic effects on oxygen consumption and bile flow in isolated skate liver
Authors: Reed J. S. , Smith N. D. , Boyer J. L.
Published: December 2017

A technique is described for perfusion of livers from the little skate, Raja erinacea, in the isolated state at 15 degrees C utilizing a recirculating, well-oxygenated elasmobranch Ringer solution. Bile flow and oxygen consumption were optimal and remained relatively constant over a 4- to 5-h perfusion at portal vein pressures of 2.5-5.0 cm Ringer. At these pressures, bile flow rates were comparable to values previously observed in the free-swimming skate. In contrast to mammalian species, bile secretion in the elasmobranch is particularly sensitive to small changes in perfusion pressure. Hepatic clearance of sulfobromophthalein and [14C]sodium taurocholate demonstrated initial fractional disappearance rates that were also similar to values obtained in vivo. Only small amounts of sulfobromophthalein appeared in bile by 5 h, whereas 78.5 +/- 6.5% of [14C]sodium taurocholate was recovered in bile at this time. These experiments establish portal vein perfusion pressures for study of skate livers in the isolated state in which oxygen consumption is maximal and organic anion clearance from perfusate to bile exceeds values obtained in vivo.
Comparison of vitamin D and 25-hydroxyvitamin D absorption in the rat
Authors: Sitrin M. D. , Pollack K. L. , Bolt M. J. , Rosenberg I. H.
Published: December 2017

We have studied the intestinal absorption of physiological amounts of vitamin D and 25-hydroxyvitamin D [25(OH)D3] in vivo from jejunal sacs in rats with thoracic and bile duct cannulas. Under all test conditions, absorption of 25(OH)D was greater than absorption of vitamin D. The majority of absorbed vitamin D and 25(OH)D was transported from the intestine in portal blood rather than lymph. When the luminal fluid contained 2.5 mM oleic acid and monoolein, the presence of taurocholate did not affect total intestinal absorption of vitamin D or 25(OH)D but increased recovery of vitamin in lymph. When luminal fat content was increased to 10 mM oleic acid and monoolein, total absorption of both vitamin D and 25(OH)D was enhanced by taurocholate. No significant metabolism of vitamin D or 25(OH)D occurred during absorption and transport in lymph. Fifty-three percent of lymph vitamin D was found in the chylomicron fraction, compared with only 13% of 25(OH)D. Inhibition of chylomicron synthesis by cycloheximide decreased vitamin D absorption by 46% but diminished 25(OH)D absorption by only 30%. These differences in behavior of vitamin D and 25(OH)D during absorption may explain the superior absorption of 25(OH)D in patients with malabsorption.
A pattern for gastric emptying in mice
Authors: Moreto M. , Guzman L. , Diez A.
Published: December 2017

Gastric emptying was studied in CD-1 mice weighing 15-30 g. Mice were fed a nonabsorbable test meal consisting of radioactive barium sulfate suspended in 1.5% methylcellulose. The amount of test meal remaining in the stomach was determined 1, 2, 5, and 10 min after the administration. The initial rates of emptying were significantly higher in the groups weighing 15-20 g body wt. In all groups, 50% of the radioactivity administered was emptied in less than 5 min. The gastric emptying figures obtained were adjusted to three general equations: exponential, hyperbolic, and parabolic. The best correlation coefficients were obtained with the parabola, although this pattern of emptying is not completely satisfactory because it has a minimum before the 10th min. The comparison of the exponential and hyperbolic patterns, in terms of both the correlation coefficients and the "starting indexes," showed that the hyperbola describes the data more closely. No sex differences were observed.
Endogenous gastric mucosal prostaglandins: their role in mucosal integrity
Authors: Ligumsky M. , Grossman M. I. , Kauffman G. L.
Published: December 2017

These studies were designed to determine the role of endogenous gastric mucosal prostaglandins (PG) in maintaining mucosal integrity. Vagally denervated, separated pouches of gastric fundic mucosa in unanesthetized dogs were irrigated with either acetylsalicylic acid (ASA) or salicylic acid (SA) (0, 2.5, 5.0, 10.0, 20.0, and 40.0 mM) in 150 mM HCl. Transmucosal potential difference (PD) and net H+, Na+, and K+ flux were measured. Mucosal ex vivo generation of 6-oxo-PGF1 alpha, PGE2, and PGF2 alpha was measured by radioimmunoassay in mucosal biopsies taken after exposure to each agent. No difference in PD or net H+, Na+, or K+ flux was observed between pouch irrigation with ASA or SA at 2.5-20.0 mM concentrations. Net H+ and Na+ flux was significantly greater (P less than 0.01) after irrigation with 40 mM SA than with 40 mM ASA. No significant reduction in gastric mucosal ex vivo generation of 6-oxo-PGF1 alpha (range, 65-98 ng.g-.min-1), PGE2 (range, 250-326 ng.g-1.min-1), or PGF2 alpha (range, 115-156 ng.g-1.min-1) was observed after pouch irrigation with all concentrations of SA. In comparison, gastric mucosal ex vivo generation of 6-oxo-PGF1 alpha (range, 75-2 ng.g-1.min-1), PGE2 (range, 22-3 ng.g-1.min-1), and PGF2 alpha (range, 40-2 ng.g-1.min-1) was significantly reduced after irrigation with all concentrations of ASA. From these data, we conclude that the activity of endogenous gastric prostacyclin, PGE2 alpha, and PGF2 alpha is not a prerequisite for mucosal integrity as measured by PD and net cationic flux.