bluuebunny/crossref_metadata_2025 huggingface dataset:
Receptors for vasoactive intestinal peptide and secretin on rat pancreatic acini
Authors: Bissonnette B. M. , Collen M. J. , Adachi H. , Jensen R. T. , Gardner J. D.
Published: December 2017

In dispersed acini from rat pancreas, binding of 125I-labeled vasoactive intestinal peptide and 125I-labeled secretin was relatively rapid, reversible, saturable, and temperature dependent. The rate of dissociation of bound 125I-labeled peptide was not a function of the concentration of free vasoactive intestinal peptide or secretin, indicating that the apparent affinities of these labeled peptides for their binding sites do not depend on the extent of receptor occupation. Four classes of receptors are required to account for the actions of vasoactive intestinal peptide and secretin on enzyme secretion, cellular cAMP, and binding of 125I-vasoactive intestinal peptide and 125I-secretin. One class has a high affinity for vasoactive intestinal peptide, and occupation of this class of receptors causes increased cellular cAMP and stimulation of amylase secretion. A second class has a low affinity for vasoactive intestinal peptide and for secretin, and occupation of these receptors does not cause changes in cAMP or amylase secretion. A third class of receptors has a high affinity for secretin, and occupation of these receptors causes increased cAMP and stimulation of amylase secretion. A fourth class of receptors has a low affinity for secretin, and occupation of these receptors causes stimulation of amylase secretion by a non-cAMP-mediated mechanism.
Positional requirements for anionic charge for ileal absorption of bile salt analogues
Authors: Lack L. , Tantawi A. , Halevy C. , Rockett D.
Published: December 2017

Previous structure-activity studies of the ileal bile salt cotransport system have suggested the idea that a coulombic interaction occurs between the negative charge of the bile salt and a cationic site on the carrier. Evidence included observations that modified bile salts with uncharged, cationic, or zwitterionic side chains were poorly transported. They did interact with this system as evidenced by their abilities to inhibit transport. Another prerequisite for coulombic interaction is positional (side-chain) specificity for the anionic grouping. [14C]chenodeoxycholyl-N-ethanolamide-O-sulfate and the 3 alpha-sulfate ester of chenodeoxycholyl-N-ethanolamide were tested for their in vivo absorption from the jejunums and ileums of anesthetized guinea pigs. Active ileal transport was estimated by subtracting jejunal absorption (passive) from ileal absorption (active and passive). Translocation of the anionic SO4(-) radical from the side chain to the 3 alpha position of the steroid decreased active ileal absorption by 95%, demonstrating a positional requirement for the anionic group for optimal transport.
Effect of dietary sucrose on synthesis and degradation of intestinal sucrase
Authors: Riby J. E. , Kretchmer N.
Published: December 2017

Rates of synthesis and degradation of sucrase-isomaltase were measured along the crypt-villus unit of intestinal mucosa of rats fed either a high-sucrose or a carbohydrate-free diet. The objective of the study was to investigate i) the biochemical basis for the accumulation of sucrase during migration and differentiation of the enterocyte, leading to changes in distribution of activity of sucrase along the villus, and ii) the mechanism for the adaptation of sucrase activity to the amount of dietary carbohydrate. The results indicate that synthesis of sucrase is more rapid than degradation at the crypt-villus junction and in the lower part of the villus, producing a progressive accumulation of enzyme. The decreased activity at the tip of the villus is the consequence of a decided diminution of synthesis while the rate of degradation remains elevated. In rats fed a diet high in sucrose, the increased activity (3.25 times) is associated with much more rapid synthesis (2.6 times), while degradation is only slightly slower (0.8 times) than in those animals deprived of carbohydrate.
Intestinal ion transport and intracellular pH during acute respiratory alkalosis and acidosis
Authors: Kurtin P. , Charney A. N.
Published: December 2017

Acute respiratory alkalosis and acidosis alter rat ileal and colonic but not jejunal electrolyte transport. To examine the role of altered intracellular pH, pHi, and HCO3 concentration, (HCO3)i, we measured pHi in mucosa scraped from the jejunum, ileum, and colon of anesthetized, mechanically ventilated Sprague-Dawley rats. During states of respiratory alkalosis (Pco2 24.9 +/- 0.8 mmHg, pH 7.586 +/- 0.014), respiratory acidosis (Pco2 67.8 +/- 1.2 mmHg, pH 7.228 +/- 0.007), and normocapnia (Pco2 41.1 +/- 0.7 mmHg, pH 7.401 +/- 0.006), pHi was measured by determining the distribution of 5,5-dimethyl[2-14C]oxazolidine-2,4-dione, using [3H]inulin as a marker of extracellular space. (HCO3)i was calculated using portal vein Pco2. In the ileum, the pHi of 6.901 +/- 0.029 was similar in alkalosis [(HCO3)i 5.4 +/- 0.3 mM], acidosis [(HCO3)i 12.4 +/- 0.6 mM], and normocapnia [(HCO3)i 8.6 +/- 0.8 mM). In both the jejunum and colon, pHi was increased in alkalosis [pHi 6.998 +/- 0.038, (HCO3)i 6.7 +/- 0.6 mM] and decreased in acidosis [pHi 6.789 +/- 0.024, (HCO3)i 10.4 +/- 0.6 mM] as compared with normocapnia [pHi 6.915 +/- 0.026, (HCO3)i 8.9 +/- 0.7 mM] (colon data given). Net electrolyte transport measured by in vivo perfusion revealed that ileal and colonic, but not jejunal, net Na and Cl absorption was decreased during alkalosis and increased during acidosis. These data suggest that, during respiratory acidosis and alkalosis, pHi is maintained in a qualitatively similar way in the jejunum, ileum, and colon with quantitatively greater or lesser changes in (HCO3)i.(ABSTRACT TRUNCATED AT 250 WORDS)
Mechanisms of transport of L-histidine and beta-alanine in hamster small intestine
Authors: Navab F. , Beland S. S. , Cannon D. J. , Texter E. C.
Published: December 2017

Whole rings of hamster jejunum and ileum were used to study the uptake of L-histidine (L-His) and beta-alanine (beta-Ala), the constituents of the dipeptide carnosine. The rate of uptake of L-His and beta-Ala (1 mM) was not significantly different in the jejunum compared with the ileum. Results of total influx (2 min) of 0.5-100 mM L-His suggested that transport was by more than one pathway, and the contribution of nonmediated component was calculated to be 0.24 mumol X g-1 X 2 min-1 X mM-1 for both jejunum and ileum. The apparent affinity of L-His for a transporter was higher in the ileum (K iota, 8.0 mM) than the jejunum (Kt, 11.7 mM). Influx (2 min) of beta-Ala was found to be linearly related to substrate concentration over the range 0.5-100 mM. The Kd (rate constant for nonmediated uptake of beta-Ala) was 0.23 and 0.14 mumol X g-1 X 2 min-1 X mM-1 for jejunum and ileum, respectively. Steady-state (20-min) uptake of L-His was significantly higher in the ileum than jejunum at substrate concentrations of 75 mM. L-His accumulated in the tissue up to a medium concentration of 50 mM in the jejunum and 75 mM in the ileum. In contrast, no evidence of tissue accumulation of beta-Ala was found in 20-min incubations. beta-Ala steady-state uptake in the ileum was significantly higher than in the jejunum at substrate concentrations of 30 and 75 mM.
Binding of somatostatin to pancreatic acinar cells
Authors: Esteve J. P. , Susini C. , Vaysse N. , Antoniotti H. , Wunsch E. , Berthon G. , Ribet A.
Published: December 2017

The binding of 125I-[Tyr11]somatostatin to guinea pig pancreatic acini was saturable and temperature, protein, and radioligand concentration dependent. Dissociation rate was very slow (t1/2 = 193 +/- 24 min). Scatchard analysis revealed a single class of binding sites with a Kd of 0.28 +/- 0.02 nM and a maximal binding capacity of 72 +/- 10.6 fmol/mg prot. There was a strong correlation between binding capacity and extracellular calcium concentration. Incubating acini in EGTA-containing medium with no added Ca2+ caused a 50% decrease in maximal binding capacity with a decrease in receptor affinity. Furthermore, in the absence of calcium, bound somatostatin was rapidly released (t1/2 = 14 +/- 1 min). Subcellular fractionation studies and acid treatment of acini incubated with the tracer showed that most of the somatostatin binding sites were located on the cell surface. Agents that altered cellular calcium in pancreatic acini, such as analogues of cholecystokinin and cholinergic agents, also inhibited the binding of 125I-[Tyr11]somatostatin by a calcium-dependent process. We conclude that somatostatin binds to specific plasma membrane receptors to form a slowly reversible complex that is highly reactive with calcium. Cell calcium-mobilizing agents decrease the affinity of acinar somatostatin receptors for somatostatin.
Oxygen radicals: effects on intestinal vascular permeability
Authors: Parks D. A. , Shah A. K. , Granger D. N.
Published: December 2017

There is now a considerable amount of evidence in the literature implicating oxygen-derived free radicals in the vascular permeability changes associated with intestinal ischemia. To directly assess the effects of oxygen radicals on vascular permeability, hypoxanthine-xanthine oxidase, an enzyme-substrate system known to generate oxygen free radicals, was infused into the arterial supply of autoperfused segments of cat ileum. The osmotic reflection coefficient (sigma d) of intestinal capillaries to total plasma proteins was estimated from the steady-state relationship between lymph-to-plasma total protein concentration ratio and lymph flow. Intra-arterial infusion of hypoxanthine-xanthine oxidase reduced sigma d from a control value of 0.92 to 0.66, indicating an increased vascular permeability. This increase in vascular permeability was significantly attenuated by the addition of superoxide dismutase (sigma d = 0.86), a specific scavenger of superoxide anion (O2-), or dimethylsulfoxide (sigma d = 0.83), the hydroxyl radical (OH X) scavenger, to the infusate. The results of this study indicate that oxygen-derived free radicals, generated by the reaction of hypoxanthine with xanthine oxidase, increase intestinal vascular permeability to an extent comparable with that observed in preparations subjected to 1 h of ischemia.
Intestinal uptake of trypsin in newborn and weaned rabbits
Authors: Udall J. N. , Bloch K. J. , Newman A. P. , Dixon M. , Walker W. A.
Published: December 2017

Earlier studies have shown that the uptake of intact proteins from the intestinal lumen into the systemic circulation is increased in neonates. The present experiments tested the uptake of trypsin in newborn compared with 4-wk-old weaned rabbits. Trypsin (200 mg/100 g body wt) was administered by gavage to newborn and 4-wk-old rabbits. Four hours later, the tryptic activity and immunoreactive trypsin (i-trypsin) content of serum from newborn rabbits exceeded that of the older animals. After Sephadex G-200 gel filtration of serum from animals gavaged with trypsin, tryptic activity was detected in the excluded volume (presumably reflecting trypsin bound to alpha 2-macroglobulin), and i-trypsin was detected in the included volume (presumably reflecting trypsin bound to alpha 1-antitrypsin). In vitro experiments demonstrated that large amounts of trypsin were required to overwhelm the antiprotease present in normal rabbit serum. We suggest that complete or partial deficiencies of serum protease inhibitors may permit proteases taken up from the intestinal lumen of the neonate to circulate, reach the liver, and induce tissue injury at this site.
Proteins in bile: how they get there and what they do
Authors: LaRusso N. F.
Published: December 2017

Experimental hepatologists have recently directed increasing attention to biliary proteins. Studies have been performed to clarify which proteins are in bile, how they get there, and what they do. Results derived with a variety of analytical techniques and several experimental models indicate that there are many individual proteins in bile; some get there from plasma across hepatocytes via specific transport processes involving vesicles, while others are derived directly from cells in the liver. It appears that some proteins are released into bile after hepatocyte degradation while others may have important and specific functions. Quantitative or qualitative abnormalities of certain biliary proteins could be important in the pathophysiology of selected diseases.
Effect of streptozotocin-induced diabetes on bile acid sulfation in male rat liver
Authors: Kirkpatrick R. B. , Kraft B. G.
Published: December 2017

The sulfation of bile acids is hormone dependent, being increased in females and ethynylestradiol (EE)-treated males compared with normal males. Diabetes causes significant alterations in estrogen metabolism and uterine estrogen receptor kinetics. Male rats were given streptozotocin (90 mg/kg) and diabetes was verified. An increase in hepatic bile acid sulfotransferase (BAST) activity was significant by 6 days and continued to increase to 29 days. This increase was prevented by insulin replacement. Administration of EE (6.0-600 micrograms X kg-1 X day-1) to normal male rats resulted in a significant increase in hepatic BAST activity; however, administration of similar doses of EE to diabetic males failed to further increase activity levels over the already-elevated levels in the diabetic controls. This increase in in vitro specific activity was accompanied by an increase in the biliary excretion of lithocholate 3-sulfate and taurolithocholate 3-sulfate in 21-day-diabetic animals. Bile flow and total bile acid excretion were also markedly increased in the diabetic animals. The data indicate that streptozotocin-induced diabetes causes a significant increase in hepatic BAST activity. These findings are consistent with an alteration in hepatic estrogen action in streptozotocin-induced diabetes.
Increasing inhibition of hepatic protein secretion by colchicine during development
Authors: Kaufman S. S. , Tuma D. J. , Sorrell M. F. , Vanderhoof J. A.
Published: December 2017

Colchicine and other antimicrotubular drugs have been shown to impair plasma protein secretion by fetal rat liver at late gestation (day 21) markedly less than by the mature organ. In the present study, the effect of colchicine on plasma protein secretion by liver slices was determined at several times during rat development. Secretion of [14C]leucine-labeled albumin and [3H]glucosamine-labeled glycoproteins was only minimally impaired (20%) by colchicine (50 microM) on gestation day 19. Inhibition of protein secretion increased to about 40% just before birth and remained unchanged throughout the perinatal period. Inhibition increased thereafter until the maximum effect (75%) was first observed 28 days after birth. Studies in which [3H]-colchicine was used indicated that neither reduced colchicine levels in tissue nor reduced affinity of tubulin for colchicine caused the diminished impairment of secretion in immature liver. These findings suggest that participation of microtubules in liver plasma protein secretion is reduced during development and that full participation is delayed beyond the perinatal period in this species.
Hepatic clearance of rat plasma intestinal alkaline phosphatase
Authors: Young G. P. , Rose I. S. , Cropper S. , Seetharam S. , Alpers D. H.
Published: December 2017

The mechanism and route of clearance of intestinal alkaline phosphatase from plasma have been studied in rats to define the magnitude of hepatic extraction and biliary excretion of the enzyme. Plasma clearance, tissue distribution, and biliary excretion of enzyme were followed after intravenous administration of physiological amounts of 125I-labeled rat intestinal alkaline phosphatase. The plasma disappearance curve was biphasic; the initial phase was rapid, during which 50% of injected enzyme was selectively extracted by the liver over 5 min. Less than 4% of total hepatic radioactivity was excreted into bile over 80 min; this was shown by chromatographic analysis to be degraded enzyme only. Rapid clearance of enzyme could be significantly slowed by injection of large amounts of mannan or N-acetylglucosamine-bovine serum albumin, but not by desialylated fetuin, demonstrating that clearance was probably mediated by mannose/N-acetylglucosamine-specific receptors. It is concluded that, under physiological conditions, rat plasma intestinal alkaline phosphatase is rapidly cleared from the circulation by the liver. However, biliary excretion of undergraded enzyme is negligible, and a physiologically significant enterohepatic circulation seems most unlikely.
Mechanism and regulation of transcellular potassium transport by the colon
Authors: Smith P. L. , McCabe R. D.
Published: December 2017

The mechanisms by which the colon handles potassium have been the subject of controversy for several years. However, recent studies have provided compelling evidence supporting the presence of active transcellular mechanisms for potassium transport by the colon. These studies have demonstrated that active uptake mechanisms for potassium exist at both the apical and basolateral membranes. Thus, depending on the conditions or the segment of colon studied, both active potassium absorption and secretion can be demonstrated. In addition, results have been obtained demonstrating that active potassium transport by the colon is regulated by endogenous mediators via modulation of intracellular cAMP and/or calcium levels. However, the mechanisms by which potassium exits across either cell membrane and the mechanisms by which intracellular mediators regulate active potassium uptake processes and/or potassium exit are not well understood.
Bile acid efflux precedes mucosal barrier disruption in the rabbit esophagus
Authors: Schweitzer E. J. , Harmon J. W. , Bass B. L. , Batzri S.
Published: December 2017

In a rabbit model of esophagitis, bile acids are one of the agents capable of disrupting the normal esophageal mucosal barrier to diffusion. They are of particular interest because they may play a central role in causing reflux esophagitis, a major clinical problem. Bile acid efflux from the lumen of the esophagus occurs when bile acids disrupt the normal esophageal barrier. Whether this entry of bile acids into the mucosa is a critical step in the pathophysiology of bile acid injury to the mucosa or a result of the injury that is occurring by some other means is unknown. To differentiate these two possibilities, the temporal relation between bile acid efflux from the esophageal lumen and disruption of the mucosal barrier was studied with an in vivo perfused model of esophagitis in anesthetized New Zealand White rabbits. Solutions containing taurocholic acid or chenodeoxycholic acid at pH 2 or 7 were perfused for 4 h while bile acid, hydrogen ion, glucose, and erythritol flux rates were measured. In each case in which the bile acid caused barrier disruption, the highest rate of bile acid efflux occurred during the 1st h of perfusion. In contrast, the increase in flux rates of hydrogen ion, glucose, and erythritol, indicators of mucosal barrier disruption, were the highest during the 2nd or 3rd h of exposure. These data suggest that entry of bile acids into the esophageal mucosa is a cause rather than an effect of the bile-induced increase in mucosal permeability.
Vasoactive intestinal polypeptide stimulation of protein secretion from rat lacrimal gland acini
Authors: Dartt D. A. , Baker A. K. , Vaillant C. , Rose P. E.
Published: December 2017

The effect of vasoactive intestinal polypeptide (VIP) on protein secretion from lacrimal gland was investigated by using acini prepared by collagenase digestion of rat exorbital lacrimal glands. Protein secretion was determined by incubating the acini for 0-40 min and analyzing the supernatant for peroxidase, a protein secreted by the rat exorbital lacrimal gland. VIP (10(-10) to 10(-7) M) stimulated secretion in a concentration-dependent manner. A maximum concentration of VIP (10(-8) M) stimulated secretion to the same extent as a maximum concentration of carbachol (10(-5) M). The cholinergic antagonist atropine at a concentration (10(-5) M) that completely abolished carbachol-induced secretion did not alter VIP-stimulated secretion. The secretory effects of maximal concentrations of VIP and carbachol were additive, but decreasing the carbachol concentration potentiated secretion. Unlike carbachol, which had no effect on the acinar cAMP level, VIP increased cAMP content sixfold. Immunohistochemical staining demonstrated VIP-like immunoreactivity in nerve fibers throughout the gland, distributed primarily around acini. We conclude that VIP-like immunoreactive nerves are present in the lacrimal gland and that VIP can stimulate protein secretion but utilizes a pathway separate from, but convergent with, that used by cholinergic agonists.
Evidence for separate sympathetic regulation of fluid absorption and blood flow in the feline jejunum
Authors: Sjovall H.
Published: December 2017

Splanchnic nerve stimulation (SNS) in cats leads to a jejunal vasoconstriction and to an enhancement of jejunal net fluid absorption. We tested the possibility that the sympathetic fibers to the transporting epithelium might use a ganglionic transmission mechanism different from the one utilized by the jejunal vasoconstrictor nerves. The splanchnic nerves were stimulated before and after a dose of hexamethonium sufficient to entirely block the intestinal vasoconstrictor fibers. However, SNS still increased net fluid absorption in these hexamethonium-treated animals. The hexamethonium-resistant increase in fluid absorption during SNS was a neurogenic effect on the jejunal segment, as it was eliminated by mesenteric denervation and could be reproduced by stimulation of the nerves surrounding the superior mesenteric artery. These data indicate that the rate of jejunal fluid absorption may be regulated by sympathetic fibers functionally distinct from the intestinal vasoconstrictor nerves.
Polyamines and intestinal growth: absolute requirement for ODC activity in adaptation during lactation
Authors: Yang P. , Baylin S. B. , Luk G. D.
Published: December 2017

Ornithine decarboxylase (ODC), through the regulation of polyamine biosynthesis, is important in cell proliferation and differentiation. We followed intestinal mucosal ODC activity in lactating Lewis rats and correlated the ODC levels with the characteristic small intestinal adaptive changes accompanying lactation. During the first 14 days of lactation, mucosal ODC activity increased, with the maximal increase on day 5 corresponding to the time of maximal morphological intestinal adaptation. In animals given the specific inhibitor of ODC, alpha-difluoromethylornithine (DFMO), intestinal mucosal ODC activity was inhibited, and intestinal adaptation was suppressed, with marked diminution of the adaptive increase in mucosal weight and thickness especially in crypt depth. Our results suggest that ODC activity plays an essential role in mucosal hyperplasia during the intestinal adaptation accompanying lactation, possibly through the stimulation of crypt cell proliferation.
Maturational increases and decreases in acid secretion in the rat
Authors: Ackerman S. H. , Shindledecker R. D.
Published: December 2017

We compared basal acid output (BAO) and maximally stimulated acid output (MAO) in 15-, 30-, and 100-day-old anesthetized rats. At each age we measured BAO and MAO in response to six different stimuli, pentagastrin (120 micrograms X kg-1 X h-1), bethanechol (1 mg X kg-1 X h-1), histamine (8 mg X kg-1 X h-1), the H2-receptor agonist impromidine (0.9 mumol X kg-1 X h-1), hypothermia (30 +/- 2 degrees C core temperature), and pyloric ligation, and we determined H+ output by continuous perfusion of the gastric lumen of anesthetized rats. Both weight-adjusted and absolute BAO were significantly greater in 30-day-old rats than in 15- or 100-day-old rats. Although 30-day-old rats had only one-fourth the fundic mass of 100-day-old rats, they could secrete two to three times more H+ per hour. These differences in MAO persisted even after subtracting BAO. Anatomic data indicate that these age-related changes do not correspond to changes in mucosal mass or parietal cell mass.
Influence of bile acid structure on bile flow and biliary lipid secretion in the hamster
Authors: Gurantz D. , Hofmann A. F.
Published: December 2017

A comprehensive study of the influence of bile acid structure on bile flow and biliary lipid secretion was carried out by infusing pure bile acids at a physiological rate into the proximal small intestine of a bile fistula hamster. Twelve individual bile acids, cholate (C), ursocholate (UC), chenodeoxycholate (CDC), and ursodeoxycholate (UDC) as their glycine (G), taurine (T), or unconjugated form, were studied so that influence of the hydroxy substituents as well as side-chain structure could be defined. The pattern of bile acid output was dependent on bile acid structure and reflected the site and rate of intestinal absorption. Conjugated bile acid output was delayed because of late ileal absorption, and TUC was poorly absorbed. Unconjugated trihydroxy bile acids, C and UC, also exhibited a delay in absorption, while CDC and UDC were absorbed immediately and achieved the highest bile acid output. Unconjugated bile acids were conjugated initially mostly with taurine and then mostly with glycine. The effect of glycine conjugates of each bile acid on bile flow and biliary lipid secretion was similar to that of their corresponding taurine conjugates. All conjugated bile acids induced a similar rate of bile flow (9–15 microliter bile/mumol bile acid), but unconjugated bile acids other than C induced more flow (20–25 microliter bile/mumol bile acid) than their corresponding conjugates. Conjugates of the dihydroxy bile acids induced a greater secretion of phospholipid and cholesterol than cholyl conjugates, whereas conjugates of UC were unique in inducing extremely low phospholipid and cholesterol secretion. For an increase of 1 mumol X min-1 X kg-1 in bile acid output, the increase in phospholipid secretion was 0.072 mumol X min X kg for GCDC and TCDC; 0.051 mumol X min-1 X kg-1 for GUDC and TUDC; and 0.030 mumol X min-1 X kg-1 for GC and TC. Increase in cholesterol output per mumol X min-1 X kg-1 of bile acid output was 0.013 mumol X min-1 X kg-1 for GCDC and TCDC, 0.011 mumol X min-1 X kg-1 for GUDC and TUDC, and 0.005 mumol X min-1 X kg-1 for GC and TC. In general, unconjugated bile acids induced more phospholipid and cholesterol than their corresponding conjugates; however, the rank-order effect of the steroid nucleus substituents was similar to that observed for the respective conjugates. These results indicate that both nuclear and side-chain structure influence the enterohepatic circulation and biliary secretory properties of bile acids.(ABSTRACT TRUNCATED AT 400 WORDS)
Effects of sham feeding, bethanechol, and bombesin on somatostatin release in dogs
Authors: De Graef J. , Woussen-Colle M. C.
Published: December 2017

In seven conscious dogs with esophagostomies and gastric cannulas, the acid, gastrin, and somatostatinlike immunoreactivity (SLI) responses to 5-min sham feeding with or without pretreatment with atropine sulfate (20 and 100 micrograms/kg) were measured. The responses to bethanechol (100 micrograms X kg-1 X h-1), to bombesin (0.5 micrograms X kg-1 X h-1) with or without pretreatment with atropine sulfate, and to a combined stimulation with bethanechol and bombesin were also measured. Sham feeding resulted in an increase in plasma SLI concentration (basal level, 20.4 +/- 4.2 pg/ml; maximally stimulated level, 46.8 +/- 5.6 pg/ml; P less than 0.01). After the injection of atropine the integrated SLI response to sham feeding was significantly decreased but not suppressed. Infusion of bethanechol did not alter SLI plasma levels. Bombesin infused alone increased the plasma SLI concentration (basal level, 15.6 +/- 2.3 pg/ml; maximally stimulated level, 55.6 +/- 10.3 pg/ml; P less than 0.01). The integrated SLI response to bombesin was significantly decreased by atropine but not significantly changed by bethanechol. These studies show that sham feeding and bombesin release somatostatin. They suggest that somatostatin release is largely under vagal-cholinergic control.
Regulation of amiloride-sensitive electrogenic sodium transport in the rat colon by steroid hormones
Authors: Will P. C. , Cortright R. N. , DeLisle R. C. , Douglas J. G. , Hopfer U.
Published: December 2017

The role of steroids in the regulation of colonic sodium transport was examined by infusing steroids into adrenalectomized (ADX) rats and evaluating the short-circuit current (ISC) in vitro. Amiloride-sensitive ISC was induced by aldosterone and corticosterone with half-maximal doses (ED50) of 2 and 260 micrograms X kg-1 X h-1), respectively. Synthetic glucocorticoids such as methylprednisolone (33 mg/kg) and dexamethasone (ED50 = 30 micrograms X kg-1 X h-1) were also effective. Supramaximal doses of aldosterone (7.5 times ED50) for 24 h increased the total ISC (7-fold), the amiloride-sensitive ISC (366-fold), and the conductance (2-fold), as well as the potassium-stimulated phosphatase activity (2-fold) (reported previously). Compared with aldosterone, supramaximal doses of dexamethasone (4 times ED50) produced greater increases in the total ISC (15-fold) and the amiloride-sensitive ISC (674-fold). In contrast to aldosterone, dexamethasone also increased the amiloride-insensitive ISC (3-fold). Glucocorticoid action was not mediated by insulin since the ISC from diabetic ADX rats was increased by dexamethasone to a similar extent (11-fold) as in nondiabetic rats. Estradiol, progesterone, and testosterone did not stimulate the colonic ISC of ADX rats. The ED50 values of corticosterone and aldosterone, measured in terms of amiloride-sensitive sodium transport, produced serum levels that were slightly above those of unstressed, adrenal-intact animals and thus must be considered physiological. It is concluded that at physiological levels both steroids may mediate amiloride-sensitive sodium transport in the rat colon. However, as judged from changes in serum steroid levels, aldosterone is the physiological regulator of elevated sodium absorption in sodium deficiency.
Amiloride-sensitive salt and fluid absorption in small intestine of sodium-depleted rats
Authors: Will P. C. , Cortright R. N. , Groseclose R. G. , Hopfer U.
Published: December 2017

Secondary hyperaldosteronism produced by Na+ depletion was associated with increases in salt and fluid absorption in both the small intestine and the distal colon but not in the cecum and the proximal colon. Because these changes had not been documented for the small intestine, this study focused on the regulation of this tissue. Increased NaCl and water absorption was expressed in vitro by increases in short-circuit current and transepithelial potential and in vivo by increased fluid absorption and a decreased luminal content of Na+ and water. For example, the short-circuit current in the ileum of Na+-depleted rats was 2-fold that of adrenalectomized and 1.3-fold that of adrenal-intact control animals. The short-circuit current was inhibitable 24 +/- 14% by micromolar concentrations of amiloride in Na+-deficient animals compared with 1 +/- 3% in control animals. Similarly, ileal fluid absorption in vivo was 2.3-fold higher in Na+-deficient relative to control animals. The additional fluid absorption was sensitive to 50 microM amiloride, whereas amiloride had no effect in control animals. Furthermore, the Na+ content of the chyme from the ileum of Na+-deficient animals was about half that of controls. These results suggest that mineralocorticoids can induce the amiloride-sensitive Na+ transporter in the small intestine and that this type of epithelial salt transport can become a major pathway for salt retention by the small intestine.
Lipase secretion from dispersed rabbit gastric glands
Authors: Fink C. S. , Hamosh M. , Hamosh P. , DeNigris S. J. , Kasbekar D. K.
Published: December 2017

We have measured gastric lipase activity in dispersed glands of rabbit stomach by quantitating the hydrolysis of tri[3H]olein. Lipase activity in isolated gastric glands was 200-400 nmol [3H]oleic acid released per milligram dry weight per minute. The percentage of lipase activity released during incubation for 30 min at 37 degrees C under basal conditions was 1.5-4.5%. Lipase release was stimulated by secretagogues: 10 nM cholecystokinin octapeptide (CCK-8) and 100 microM carbachol led to four- to sixfold and two- to threefold higher enzyme secretion, respectively, while histamine had no effect. Carbonyl cyanide m-chlorophenylhydrazone (30 microM) completely inhibited the CCK-8-induced lipase release, indicating that lipase secretion is dependent on mitochondrial oxidative energy; dibutyryl cGMP (1 mM) inhibited 1 nM CCK-8-stimulated but not 100 microM carbachol-stimulated secretion; atropine (1 microM) had the opposite effect. These studies suggest that secretion of lipase from isolated gastric glands is stimulated by at least two receptor mechanisms. These studies show that a lipase that hydrolyzes long-chain triglyceride is secreted by rabbit stomach mucosa and that the secretion of gastric lipase is stimulated by two different receptor mechanisms.
Characterization of conductive pathways in guinea pig distal colon in vitro
Authors: Clauss W. , Durr J. , Rechkemmer G.
Published: December 2017

Isolated mucosal sheets of guinea pig distal colon were studied in vitro in Ussing-type chambers, using a computer-controlled voltage clamp. A conductance of 8–12 mS/cm2 and spontaneous variations of the potential difference (Vt, -4 to +6 mV) and the short-circuit current (Isc, -1.6 to +1.5 mu eq X cm-2 X h-1) were observed. With use of a green feed diet these variations could be entirely attributed to the rate of Na transport. Unidirectional Na and Cl fluxes were measured, and for Na, K, and Cl transport the individual conductances and directions were estimated from the changes in Vt and Isc, using the appropriate blockers amiloride, barium, and piretanide. The sum of the electrogenic Na, K, and Cl transport determines the spontaneous electrical behavior of this epithelium. Na transport was further characterized with transepithelial and transapical current-voltage relations. Apical Na entry occurred by diffusion, intracellular Na activity was 12 mM, and apical Na permeability was calculated as 0.02 cm/h. This study represents the first in vitro investigation of electrogenic transport in this epithelium and shows that it closely resembles transport mechanisms found in rabbit colon.
Pirenzepine-sensitive muscarinic receptors regulate gastric somatostatin and gastrin
Authors: Sue R. , Toomey M. L. , Todisco A. , Soll A. H. , Yamada T.
Published: December 2017

Pirenzepine, a newly described antagonist of selective muscarinic receptors (M1), has been shown to be a potent inhibitor of acid secretion. To determine whether this property of pirenzepine can be explained in part by its actions on hormones regulating acid secretion, we examined pirenzepine's effects on gastrin and somatostatinlike immunoreactivity (SLI) secretion from the isolated, perfused rat stomach. Carbachol at a dose of 10(-6) M inhibited SLI and stimulated gastrin secretion. Both atropine and pirenzepine reversed these effects in a dose-dependent fashion with D50 values of 1 X 10(-9) and 1 X 10(-7) M, respectively, against gastrin stimulation and 1 X 10(-8) and 1 X 10(-7) M, respectively, against SLI inhibition. Pirenzepine caused a progressive parallel rightward shift in the dose-response curves for SLI inhibition and gastrin stimulation by carbachol, suggesting competitive inhibition. The apparent inhibitory constant (ki) was calculated to be approximately 2 X 10(-9) M. These results indicate that gastrin and SLI release from the stomach is governed by high-affinity muscarinic receptors that are sensitive to pirenzepine. Pirenzepine's action as an acid secretory inhibitor, and possibly as an ulcer therapy drug, may be explained in part by these effects on gastric hormone regulation.
Bombesin-induced residual stimulation of amylase release from mouse pancreatic acini
Authors: Howard J. M. , Jensen R. T. , Gardner J. D.
Published: December 2017

When dispersed acini from mouse pancreas are first incubated with bombesin, washed, and then reincubated with fresh incubation solution containing no bombesin, there is significant residual stimulation of amylase release. Induction of residual stimulation is relatively rapid in that significant stimulation occurs as early as after 15's of first incubation with bombesin. Induction of residual stimulation of amylase release per se is temperature independent, but induction does occur more rapidly when acini are first incubated at 37 degrees C than when they are first incubated at 4 degrees C. Residual stimulation of amylase release persists for at least 75 min in acini that have been first incubated with bombesin at 37 degrees C. The maximal residual stimulation of amylase release obtained with pancreatic acini that have been first incubated with bombesin and then washed is 45% greater than the maximal stimulation obtained when bombesin is added directly to the incubation medium. In terms of their abilities to cause residual stimulation of amylase release, litorin and ranatensin are equal to bombesin in potency and efficacy. Gastrin-releasing peptide is approximately 70% as efficacious as bombesin in causing residual stimulation of amylase release.
Intestinal membrane lipid composition and fluidity during development in the rat
Authors: Schwarz S. M. , Hostetler B. , Ling S. , Mone M. , Watkins J. B.
Published: December 2017

We have characterized microvillus membrane (MVM) lipid composition and derived estimates of membrane fluidity using fluorescence polarization [with 1,6-diphenyl-1,3,5-hexatriene (DPH) as the probe] in MVM from the jejunum and ileum of suckling (day 14–20) and mature postweaning (day 28–49) rats. The anisotropic values are lower (i.e., increased fluidity) in MVM from jejunum and ileum of suckling rats compared with values from MVM of mature rats, suggesting a more disordered molecular environment in MVMs of suckling animals, although the ileal MVM was relatively less fluid than jejunal membranes in both groups. Anisotropic determinations in protein-free MVM liposomes demonstrate that protein-lipid interactions are major determinants of fluidity estimates. Arrhenius plots of DPH anisotropies in MVM and MVM liposomes indicate a thermotropic lipid-phase transition at 23 degrees C in mature rat jejunum and ileum; however, no clear transition point was observed in 14- to 20-day animals. In addition, both the jejunal and ileal MVM in suckling animals contained greater amounts of total lipid, cholesterol, and phospholipid per milligram protein than did mature MVM preparations. Membrane phospholipid composition changed with age, with a decrease in sphingomyelin and an increase in phosphatidylcholine in the jejunum of the postweaning animal and with similar weight ratios of saturated to unsaturated fatty acids in both age groups. The data demonstrate that the small intestinal MVM manifests both age-dependent and regional proximal-distal differences in lipid composition and biophysical properties.(ABSTRACT TRUNCATED AT 250 WORDS)
Physiological variations in canine gastric tone measured by an electronic barostat
Authors: Azpiroz F. , Malagelada J. R.
Published: December 2017

Gastric tone may mediate gastric accommodation and emptying; however, it cannot be recorded by manometric methods. We have developed an electronic barostat that maintains a constant pressure (2 mmHg) within an air-filled bag and have validated the system in vitro and in vivo. In four conscious dogs, the bag was introduced orally into the stomach, and gastric tone was monitored from the barostat as variations in intrabag volume. Simultaneously, we recorded upper gut pressure activity by implanting manometric catheters. Studies were performed in fasting and fed (200-ml solid meal) dogs. The barostat system did not distort fasting motor activity. Intrabag volume correlated with manometrically measured fundic pressure activity. However, tonic changes undetected manometrically were clearly registered by the barostat. Meal induced marked changes in gastric tone. A receptive relaxation during feeding was followed by a low-tone accommodation period. Later, the barostat registered a sustained high tone until the return of the fasting pattern. We conclude that the electronic barostat measures physiological variations in gastric tone that are not recorded by conventional systems.
Omeprazole inhibits H+ secretion by Amphiuma jejunum
Authors: White J. F.
Published: December 2017

The effect on HCO3- absorption of the substituted benzimidazole omeprazole, an inhibitor of active H+-K+ exchange, was examined in in vitro Amphiuma jejunum. HCO-3 absorption was measured using titration in short-circuited intestinal segments bathed in a Cl--free (SO2-(4)-based) medium (pH 7.40). At 1 mM omeprazole lowered the short-circuit current (Isc) and the absorptive flux of HCO3- from mucosa to serosa by about 40% over 1 h. When the serosal medium was maintained at pH 5.0, additions of omeprazole beginning at 0.1 mM caused proportional reductions of the Isc. Omeprazole also reduced intracellular potassium activity (aiK) from 74 to 59 mM and lowered the luminal membrane potential (psi m) slightly over 30 min when this was measured with double-barreled, K+-sensitive microelectrodes. After 30 min aiK and psi m tended to spontaneously revert toward control values. Galactose added to the mucosal medium (to 20 mM) stimulated the Isc equally in omeprazole-treated tissues and paired untreated control tissues. These results support the view that a fraction of the absorptive HCO3- flux (so-called) is driven by an active luminal exchange of H+ for K+.
Localization of acid microclimate along intestinal villi of rat jejunum
Authors: Daniel H. , Neugebauer B. , Kratz A. , Rehner G.
Published: December 2017

Considering the significance that pH value could have for digestive and absorptive processes, these investigations were aimed at precisely localizing the position of the acid microclimate, i.e., of proton accumulation along the surface of intestinal villi. The determinations were carried out under microscopic control on jejunal segments of rats incubated at 25 degrees C in O2-saturated phosphate buffer (pH 7.4). Specially manufactured antimony microelectrodes (tip diam 50 microns) and calomel reference electrodes were used for pH registration. Highest proton concentration (214-224 nmol/l not equal to pH 6.67-6.65) was found 10-100 microns below the tip of the villus in the zone of digestive and absorptive epithelial cells. Toward the crypt, a steep decrease of proton concentration was registered with alkaline values 200 microns below the villus tip. Toward the bulk phase, the decrease of the proton concentration was moderate due to the existence of the unstirred water layer as an effective diffusion barrier. The pH value of the bulk phase was reached 440 microns over the villus tip, a distance possibly identical to the thickness of the unstirred water layer.
Opiate nerves mediate feline pyloric response to intraduodenal amino acids
Authors: Reynolds J. C. , Ouyang A. , Cohen S.
Published: December 2017

Intraluminal pressures and myoelectric activity were recorded from the feline antrum, pylorus, and duodenum in response to intraduodenal amino acid solutions. Mixed amino acids (0.02 mg/ml, 3.0 ml) increased the amplitude of pyloric contractions (59.7 +/- 7.9 mmHg) and pyloric spike activity (73.7 +/- 6.8% of slow waves with spike activity) compared with a saline control (P less than 0.001). The selectivity of these responses was determined with specific amino acids. L-Tryptophan (10 or 40 mM) produced a response similar to the mixed amino acid response, while L-phenylalanine or L-glycine (10 or 40 mM) had no effect. Intra-arterial tetrodotoxin, intraluminal ethyl aminobenzoate, or intravenous naloxone (1.0 mg/kg) abolished the pyloric responses to amino acids (P less than 0.02). Bilateral cervical vagotomy had no effect. Cholecystokinin octapeptide (CCK-OP) produced dose-dependent increases in the amplitude of pyloric contractions and in pyloric spike activity. The ED50 dose of CCK-OP (1.0 microgram/kg iv) gave an increase in pyloric pressure of 155.6 +/- 49.9 mmHg and in spike activity of 77.7 +/- 9.4%, similar to mixed amino acids or tryptophan. These effects of CCK-OP were not antagonized, however, by a dose of naloxone (1.0 mg/kg) that blocked the maximal pyloric response to leucine-enkephalin. We concluded intraduodenal mixed amino acids or tryptophan increase phasic, spike-dependent pyloric contractions in the cat via nonvagal, naloxone-sensitive neural pathways, phenylalanine, a structurally similar essential amino acid, had no effect on the feline gastroduodenal junction, and the pyloric responses to exogenous CCK-OP are mediated by pathways distinct from the responses to tryptophan or mixed amino acids.
Variability of lower esophageal sphincter pressure in the fasted unanesthetized opossum
Authors: Holloway R. H. , Blank E. , Takahashi I. , Dodds W. J. , Hogan W. J. , Dent J.
Published: December 2017

The opossum has served as a useful animal model for in vivo studies of lower esophageal sphincter (LES) function. Previous investigations, however, have been confined to studies on anesthetized animals. In 10 opossums we investigated LES pressure during fasting cycles of the gastrointestinal migrating myoelectric complex (MMC) and examined the influences of anesthesia and feeding on LES pressure. Intraluminal pressure from the esophageal body, LES, and gastric antrum was recorded by a manometric assembly that incorporated a sleeve device. Myoelectric activity was recorded from the gastric antrum and duodenum via implanted electrodes. MMCs were readily recorded from all animals. MMC cycle length was 86 +/- 2.9 (SE) min. The LES exhibited cyclic changes in intraluminal pressure that occurred in synchrony with the gastric MMC cycle. During phase I of the gastric MMC cycle, LES pressure was essentially stable, although intermittent spontaneous oscillations at 3-4/min were sometimes noted. Forceful phasic LES contraction started during phase II of the gastric MMC, became maximal during phase III, and disappeared during phase I. The MMC-related phasic LES contraction occurred at a maximal rate of 1.4 +/- 0.05/min with amplitudes of 60-150 mmHg and were temporally associated with spike bursts and contractions in the gastric antrum. Pentobarbital sodium-induced anesthesia abolished MMC-related phasic LES activity and caused a transient rise in basal sphincter pressure. Phasic LES activity was also inhibited by atropine and feeding.(ABSTRACT TRUNCATED AT 250 WORDS)
Tauroursodeoxycholate prevents biliary protein excretion induced by other bile salts in the rat
Authors: Kitani K. , Ohta M. , Kanai S.
Published: December 2017

Biliary excretion of various proteins (5'-nucleotidase, alkaline phosphatase, lactate dehydrogenase, and albumin) was investigated in pentobarbital sodium-anesthetized rats infused with different bile salts [taurocholate (TC), taurochenodeoxycholate (TCDC), and tauroursodeoxycholate (TUDC)]. A TCDC infusion at 0.4 mumol . min-1 . 100 g body wt-1 caused much higher increases in the biliary excretion of these proteins compared with the respective values in rats that received an infusion of TC at a threefold higher rate (1.2 mumol . min-1 . 100 g body wt-1). In contrast, a TUDC infusion at 1.8 mumol . min-1 . 100 g body wt-1 showed the minimum effect on these protein leakages. A combined infusion of TCDC (0.4 mumol . min-1 . 100 g-1) and TUDC (0.6 mumol . min-1 . 100 g-1) resulted in drastic (8- to 20-fold) decreases in excretion of these enzymes and albumin compared with respective values in rats infused with TCDC alone. Similar preventive effects were observed with the addition of TUDC to the infusion of TC (1.2 mumol . min-1 . 100 g-1). These results suggest that the hepatic cytotoxic effects of TC and TCDC can be prevented by the simultaneous infusion of TUDC in rats.