bluuebunny/crossref_metadata_2025 huggingface dataset:
N-terminal fragments of CCK-(26-33) as cholecystokinin receptor antagonists in guinea pig pancreatic acini
Authors: Gardner J. D. , Knight M. , Sutliff V. E. , Jensen R. T.
Published: December 2017

In the present study we synthesized different N-terminal fragments and analogues of the C-terminal octapeptide of cholecystokinin [CCK-(26-33)] and examined their actions on dispersed acini prepared from guinea pig pancreas. None of the N-terminal fragments or analogues altered basal amylase release. Analogues of CCK-(26-32), CCK-(26-31), and CCK-(26-30) inhibited CCK-(26-33)-stimulated amylase, and there was a close correlation between the ability of an analogue to inhibit stimulated amylase and the analogue's ability to inhibit binding of 125I-cholecystokinin. N-acetyl-CCK-(26-29)-amide at concentrations as high as 100 microM did not inhibit CCK-(26-33)-stimulated amylase release or binding of 125I-CCK. For those analogues that antagonized CCK-(26-33)-stimulated amylase release the antagonism was of the competitive type and was specific for those secretagogues that interact with the cholecystokinin receptor. Removing the C-terminal amide from N-acetyl-CCK-(26-31)-amide caused a 10-fold decrease in the inhibitory potency, whereas removing the C-terminal amide from N-acetyl-CCK-(26-30)-amide did not alter the inhibitory potency of the peptide. Removing the sulfate ester from the tyrosine residue in position 27 of N-acetyl-CCK-(26-31) did not alter the inhibitory potency of the peptide, whereas removing the sulfate ester from the tyrosine residue in position 27 of N-acetyl-(26-30) caused a three- to fivefold decrease in the inhibitory potency of the peptide.(ABSTRACT TRUNCATED AT 250 WORDS)
Intestinal nerves and ion transport: stimuli, reflexes, and responses
Authors: Hubel K. A.
Published: December 2017

The effects of extrinsic and intrinsic nerves on ion and water transport by the intestine are considered and discussed in terms of their possible physiological function. Adrenergic nerves enter the small intestine via mesenteric nerves. Adrenergic tone is usually absent in tissues in vitro but is present in vivo. The nerves increase absorption in response to homeostatic changes associated with acute depletion of extracellular fluid. Cholinergic tone that reduces fluid absorption or causes secretion has been detected in the small intestine of humans, dogs, and cats and in the colon of humans. Extrinsic cholinergic fibers generally do not affect ion transport in small intestine but probably do so in colon. Whether peptides liberated in the mucosa affect enterocytes directly is not clear. Studies on humans and rabbits suggest that the role of substance P is minor. The physiological roles of vasoactive intestinal polypeptide (VIP) and somatostatin remain to be defined. Intraluminal factors also affect ion and water transport. Mucosal rubbing, distension, and cholera toxin cause fluid secretion; acid solutions in the duodenum cause alkaline secretion; these stimuli and hypertonic glucose liberate serotonin into the lumen, the mesenteric venous blood, or both. It has been proposed that the enterochromaffin cell is an epithelial sensory cell that responds to noxious stimuli within the lumen by liberating serotonin. The serotonin initiates a neural reflex through a nicotinic ganglion to liberate a secretagogue that acts on the enterocyte. The function of VIP in this proposed reflex is unclear. The variety of intraluminal stimuli that influence epithelial function implies that there is more than one type of epithelial sensory cell (or sensory mechanism). Prostaglandins may mediate the alkaline secretion caused by acid in the duodenum. There may be other effective substances. Although it has been known for years that intraluminal stimuli affect the coordination of smooth muscle functions, it is not known whether similar stimuli also influence salt and water transport as a meal traverses the alimentary canal.
Gastrin-releasing peptide: effect on exocrine secretion and release from isolated perfused porcine pancreas
Authors: Knuhtsen S. , Holst J. J. , Jensen S. L. , Knigge U. , Nielsen O. V.
Published: December 2017

The effect of gastrin-releasing peptide (GRP) on pancreatic exocrine secretion was studied by infusing it at four dose levels (0.01, 0.1, 1.0, and 10 nmol/l) into the arterial line of the isolated perfused porcine pancreas. At 1.0 nmol/l GRP stimulated protein (37-fold), fluid (13-fold), and bicarbonate secretion (12-fold). Atropine at 1 mumol/l diminished the protein secretion in response to infusion of GRP at a dose of 1 nmol/l to 45% of control. Fluid and bicarbonate responses were not affected by atropine treatment. Electrical stimulation of the vagus nerves resulted in an increase in pancreatic output of GRP and a concomitant stimulation of exocrine secretion. Infusions of acetylcholine, carbachol, pilocarpine, or dimethylphenylpiperazinium had no effect on the output of GRP, although hexamethonium abolished the response to vagal stimulation. It is concluded that GRP in conjunction with acetylcholine is likely to play a prominent part in parasympathetic regulation of pancreatic exocrine secretion.
Role of cholecystokinin in pancreatic exocrine response to intraluminal amino acids and fat
Authors: Stubbs R. S. , Stabile B. E.
Published: December 2017

Controversy continues over the relative contributions made by hormonal and neural mechanisms in the exocrine pancreatic response to ingested food. The recent description of the drug proglumide as a specific, competitive cholecystokinin (CCK)/gastrin receptor antagonist has permitted reevaluation of the role of CCK in this process. In chronic pancreatic fistula dogs, dose-response studies were performed to determine the effect of proglumide on the pancreatic responses to octapeptide of CCK (CCK-OP), intravenous bethanechol, intraduodenal amino acids, and intraduodenal fat. Pancreatic volume, protein, and bicarbonate outputs to all doses of CCK-OP were inhibited significantly (P less than 0.05) in a competitive manner, consistent with the proposed mode of action of proglumide. In contrast, proglumide caused only minor and insignificant inhibition of the output responses to intravenous bethanechol. Virtually complete inhibition to all doses of intraduodenal amino acids and fat was observed with proglumide administration. If indeed proglumide is a specific CCK receptor antagonist, these results support the hypothesis that CCK is the major mediator of the intestinal phase of exocrine pancreatic secretion.
Effect of pentagastrin on gastric mucosal histamine in dogs
Authors: Redfern J. S. , Thirlby R. , Feldman M. , Richardson C. T.
Published: December 2017

We studied the effect of pentagastrin on histamine content of gastric mucosa obtained from dogs with gastric fistulas to determine whether pentagastrin mobilizes cellular stores of histamine. Experiments were also performed on canine gastric mucosa in vitro to investigate the effects of pentagastrin on histamine release, per se. During in vivo studies basal histamine content averaged 0.9 nmol/mg wet wt tissue or 18.8 nmol/mg tissue prot. No significant difference in gastric mucosal histamine content occurred during intravenous administration of pentagastrin (6 or 16 micrograms . kg-1 . h-1) or saline (control), even though acid output from the gastric fistula increased significantly above control during pentagastrin infusion. Moreover, pentagastrin (10(-5) and 10(-8)M) did not release more histamine from gastric mucosa in vitro than the buffer (control), whereas Triton X-100 and the phorbol ester 4 beta-phorbol 12 beta-myristate 13 alpha-acetate, alone and in combination with calcium ionophore A23187, released significant amounts of histamine above control values. From these experiments we conclude that pentagastrin did not alter histamine content of canine gastric mucosa in vivo, even though acid secretion was stimulated maximally, nor did pentagastrin release histamine in vitro.
Permeability of zymogen granule membrane to protein
Authors: Rothman S. S. , Liebow C.
Published: December 2017

The evidence that the membrane of the pancreatic zymogen granule is permeable to its contained secretory proteins is outlined. Included is a discussion of the nature and characteristics of the equilibrium-dependent release of protein from isolated granules, the evidence for the permeability of the granule membrane to digestive enzyme protein in situ, and the seeming paradox that isolated granules release protein in medium similar to that thought to exist in the cell. The permeability hypothesis is reconsidered here in light of recent claims of stable nonpermeable granules.
Motility of the small intestine: a look ahead
Authors: Mathias J. R. , Sninsky C. A.
Published: December 2017

Motility of the gastrointestinal tract has become an important discipline of gastroenterology. In this paper we review important observations made during the early development of this discipline, note the current level of knowledge, and look ahead to some of the questions we believe will be addressed in the near future. Is the slow wave the action potential equivalent of the longitudinal muscle layer? How does the migrating action potential complex interrelate with the migrating myoelectric complex--are they two separate complexes under different control mechanisms? How do the myenteric plexus neurons relate to these complexes? Does the muscularis mucosa control the contraction and relaxation of the villous tips? Is there a finite area in the small intestine that can function as the pacemaker? How important are substances within the lumen in controlling motility? Finally, we emphasize the importance of structure and function of the plexus neurons in motility studies. We also stress the importance of collaboration and a multidisciplinary approach for future understanding of the mechanisms of the small intestine in health and disease.
Microelectrode studies of Necturus antral mucosa. II. Equivalent circuit analysis
Authors: Ashley S. W. , Soybel D. I. , De L. , Cheung L. Y.
Published: December 2017

Intracellular microelectrode techniques were employed to determine the equivalent circuit parameters in Necturus antral mucosa. Stable intracellular impalements were obtained using 15- to 50-M omega microelectrodes. Measured transepithelial and cellular potentials and voltage deflections produced by transepithelial current pulses were used to calculate the electrical resistances of the cell membranes and the equivalent electromotive forces (EMF) at both cell borders. The measured potentials were -4.1 +/- 0.8 mV for the entire epithelia, -41.8 +/- 5.1 mV for the apical membrane, and -45.9 +/- 5.0 mV for the basolateral membrane. Values for the resistances were 7,300 +/- 1,900 omega X cm2 for the apical, 3,990 +/- 1,170 omega X cm2 for the basolateral, and 710 +/- 40 omega X cm2 for the shunt. Assuming that the shunt EMF is zero with control Ringer solution on both sides of the tissue, the effect of this relatively low-resistance shunt on electrical parameters can be determined. The cell membrane EMFs are both oriented with the interior negative and are -1.2 +/- 9.7 mV (apical) and -69.7 +/- 11.3 mV (basolateral). The difference between these values and the measured potentials is the result of a flow of current through the shunt from serosa to mucosa, hyperpolarizing the apical and depolarizing the basolateral membranes.
Sequential disaccharidase loss in rat intestinal blind loops: impact of malnutrition
Authors: Sherman P. , Wesley A. , Forstner G.
Published: December 2017

We studied lactase, maltase, and sucrase activities in the mucosa of self-filling blind loops (SFBL) in adult rats at weekly intervals after SFBL formation in order to determine the sequence in which disaccharidase activities fall. The studies were carried out on nourished and malnourished rats and extended to a recovery period induced by antibiotics to determine the effects of malnutrition on the establishment and repair of disaccharidase deficiencies caused by bacterial overgrowth. Malnutrition was produced by feeding 50% of the intake of paired rats fed ad libitum. Disaccharidase activities were determined in SFBL from nourished and malnourished rats at 7-day intervals until pandisaccharidase deficiency was established and during a 2-wk recovery period induced by antibiotics. Maximal SFBL bacterial counts in both nourished and malnourished groups of rats and brush-border glycoprotein degradation ratios were established at 7 days. In nourished rats only lactase was deficient at 7 days; maltase and sucrase fell later and sequentially. In malnourished rats all three disaccharidases were reduced at 7 days. Disaccharidase activities in self-emptying blind loops (SEBL), used as operated controls, were not decreased 28 days after surgery. Malnutrition had no effect on disaccharidase activities in the SEBL, and malnutrition did not affect recovery rates with antibiotic therapy. We conclude that small intestinal bacterial overgrowth causes a staggered loss of disaccharidase activities beginning with the loss of lactase activity. In the presence of bacterial overgrowth, malnutrition accelerates the conversion of a mono- to a pan-disaccharidase deficiency.
Intestinal metabolism and portal venous transport of 1,25(OH)2D3, 25(OH)D3, and vitamin D3 in the rat
Authors: McDonald G. B. , Lau K. H. , Schy A. L. , Wergedal J. E. , Baylink D. J.
Published: December 2017

We compared the intestinal absorption of three vitamin D3 sterols and tested the hypothesis that the intestine hydroxylates absorbed vitamin D and transports polar metabolites in portal venous blood. Micellar solutions containing 50 nmol of a radiolabeled vitamin D3 sterol (1,25-dihydroxyvitamin D3, 25-hydroxyvitamin D3, or vitamin D3) were placed in closed jejunal segments of rats prepared with lymphatic and mesenteric venous fistulas. Venous blood loss was replaced by infusion of donor rat blood into the saphenous vein. After 1-2 h the rats were killed, and intestinal homogenates, mesenteric blood, and lymph were analyzed. The average rate of absorption of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] was two- and fivefold higher than that of 25-hydroxyvitamin D3 [25(OH)D3] and vitamin D3 (D3), respectively. Transport of hydroxylated vitamin D sterols was primarily via the venous route; the average rate of venous transport of 1,25(OH)2D3 was 18.3 X 10(2) nmol X min-1 X g-1 compared with 8.8 X 10(2) for 25(OH)D3 and 0.13 X 10(2) for D3. High-performance liquid chromatography of intestinal and plasma extracts revealed that there was 25-hydroxylation of absorbed D3, 24- and putative 1-hydroxylation of absorbed 25(OH)D3, and prompt portal venous transport of all hydroxylated metabolites. When 1,25(OH)2D3 was infused into the lumen, the composition of radiolabeled sterols found in intestinal homogenates and mesenteric venous plasma was virtually identical to that of the infusate. These studies provide in vivo evidence for the intestinal metabolism of pharmacological quantities of absorbed vitamin D3 sterols and the prompt portal venous transport of more polar metabolites.
Effects of unstirred Disse fluid, nonequilibrium binding, and surface-mediated dissociation on hepatic removal of albumin-bound organic anions
Authors: Forker E. L. , Luxon B. A.
Published: December 2017

Proceeding from the observation that organic anions bound to albumin have hepatic extraction fractions that are unexpectedly high, we have studied a distributed model that accounts for this phenomenon by invoking sites on the cell surface that catalyze the dissociation of albumin-anion complexes. The present report extends this model to include nonequilibrium binding and rate-limiting diffusion of bound anion to the cell surface. Simulation analysis of the extended model provides an unambiguous basis for interpreting the apparent intrinsic clearance of free anion. The model is fully consistent with the transport data that we obtained with rose bengal [Am. J. Physiol. 248 (Gastrointest. Liver Physiol. 11): G702-G708, 1985] but is suited to estimating only selected components of the unknown parameter vector. Uncertainties inherent in an alternate approach are discussed and illustrated.
Attenuation of trophic response to gastrin after inhibition of ornithine decarboxylase
Authors: Seidel E. R. , Tabata K. , Dembinski A. B. , Johnson L. R.
Published: December 2017

The mechanism by which the hormone gastrin induces growth of the gastrointestinal mucosa is unknown. Many hormones are inducers of ornithine decarboxylase (ODC), the rate-limiting enzyme in the synthesis of the polyamines putrescine, spermidine, and spermine. Although the exact biochemical function of the polyamines is not completely understood, they appear to be required for normal cell growth and differentiation. Rats were maintained on a liquid diet for 5 days and treated with difluoromethylornithine (DFMO, 200 mg/kg ip, 3 times/day), a selective, irreversible inhibitor of ODC, for 5 days. Half of these animals also received pentagastrin (250 mg/kg ip) during the final 3 days of the treatment schedule. DFMO alone had no effect on body weight or mucosal growth. Pentagastrin increased total RNA, DNA, and protein in the oxyntic gland and duodenal and colonic mucosa. Concurrent treatment with DFMO completely inhibited the trophic response to pentagastrin in the oxyntic gland area of the stomach and the duodenal mucosa. In contrast, DFMO was without effect on response of the colonic mucosa to pentagastrin. Pentagastrin treatment did not induce the mucosal ODC activity of the oxyntic gland area of the stomach, the duodenum, the ileum, or the proximal colon of either animals fasted for 48 h or animals maintained on a liquid diet. ODC activity was measured at 4, 8, 12, and 24 h after administration of hormone. These results suggest that, in at least the proximal bowel, the stimulation by gastrin of nucleic acid and protein synthesis requires intact polyamine synthesis but that gastrin itself does not induce ODC.
Enhancement of Na+-dependent bile acid uptake by albumin: direct demonstration in rat basolateral liver plasma membrane vesicles
Authors: Blitzer B. L. , Lyons L.
Published: December 2017

The effects of albumin on taurocholate uptake by rat basolateral liver plasma membrane vesicles were examined. With this system direct effects on carrier-mediated Na+-dependent bile acid uptake may be distinguished from nonspecific alterations in carrier-independent diffusion. Bovine serum albumin increased both the initial velocity and peak uptake of taurocholate in the presence of an Na+ gradient but did not enhance Na+-independent bile acid uptake. The effects of albumin were strikingly dependent on albumin concentration. Maximal enhancement of bile acid uptake was observed at albumin concentrations of 0.125 g/dl (18 microM) to 0.25 g/dl (37 microM), which are similar to reported values for the Kd for albumin binding to the plasma membrane. At high albumin concentrations (2.5 g/dl, 367 microM), uptake was reduced but to a lesser extent than the expected fall in free bile acid concentration. Kinetic studies showed that albumin (0.5 g/dl, 74 microM) reduced the taurocholate Km from 36.5 to 16.1 microM but did not affect Vmax, suggesting that albumin binding may increase the affinity of the bile acid receptor for taurocholate. Bovine gamma-globulin, chicken ovalbumin, and human transferrin did not enhance taurocholate uptake. Control experiments demonstrated that the mechanism of the albumin effect was not dependent on residual albumin-bound calcium and did not involve alteration of the underlying driving forces for bile acid uptake (Na+ gradient). These studies have “unmasked” an enhancing effect on taurocholate uptake by low concentrations of albumin that would not have been readily detected at higher concentrations.
Gastrointestinal myoelectric activity in conscious guinea pigs
Authors: Galligan J. J. , Costa M. , Furness J. B.
Published: December 2017

Myoelectric activity was recorded from the gastric antrum and small intestine of conscious, unrestrained guinea pigs using bipolar Ag-Ag chloride electrodes that had been previously implanted under pentobarbital sodium/Innovar anesthesia. In fasted guinea pigs, the migrating myoelectric complex (MMC) was recorded from the small intestine and was observed to propagate aborally at a speed that declined with distance from the pylorus (range of speeds of the front of phase 3: 17.5 cm/min in the duodenum to 4.1 cm/min in the ileum). The complex was not disrupted by feeding but occurred less frequently in the freely fed state (82-min cycle period in the fasted state versus 139 min in the fed state). The complex started in the duodenum and was accompanied by a brief (6.3 +/- 0.9 min) period of inhibition of antral myoelectric activity. Slow waves were also recorded from the gastric antrum (10.3 +/- 1.3/min) and the small intestine. The frequency of intestinal slow waves was uniform along the length of the bowel (26.2 +/- 1.3/min in the duodenum to 24.7 +/- 1.3/min in the ileum). It is concluded that the guinea pig is similar to other mammalian species, so far examined, in its pattern of gastrointestinal myoelectric activity.
Effect of ethanol on choline transport in rat jejunum
Authors: Hajjar J. J. , Baker E. R. , Renison D. M. , Gardner P. W. , Zirin R. , Tomicic T. K.
Published: December 2017

The effect of ethanol on choline transport across the rat jejunum was studied by intraluminal perfusion in vivo and by influx measurement across the brush-border membrane in vitro. Acute ethanol administration (4 g/kg) through a gastric tube caused an increase in net choline absorption within 1 h. The increase was prevented by pretreatment with pyrazole, an inhibitor of ethanol metabolism. Chronic ethanol administration also caused an increase in choline absorption, the effect being unrelated to the nutritional changes that occur with ethanol ingestion. In contrast, direct instillation of 0.65 M ethanol through the perfusate caused no changes in choline absorption, and the perfusion of a 1.14 M solution even decreased absorption. The in vitro influx of choline across the mucosal membrane of the isolated rat jejunum was also enhanced by pretreatment with ethanol given by gavage 1 h prior to experimentation. Similarly, the ethanol-related increase in the influx rate was inhibited by pyrazole but was unaffected by acetaldehyde or acetate. Like ethanol, pretreatment of rats with methanol stimulated the choline influx rate. The results suggest that ethanol metabolism, rather than the direct effect of ethanol by itself, stimulates the absorption and influx of choline into the rat jejunum. The effect is not produced by the primary metabolites of ethanol, acetaldehyde, or acetate but is very likely related to stimulation by other products of ethanol metabolism.
Duodenal aluminum absorption in the rat: effect of vitamin D
Authors: Adler A. J. , Berlyne G. M.
Published: December 2017

Aluminum absorption by the duodenum was studied with an in vivo isolated gut segment technique in vitamin D-deficient and vitamin D-replete rats. Aluminum uptake could be resolved into saturable and nonsaturable components. Both groups demonstrated an identical nonsaturable mechanism with an aluminum uptake of approximately 23% of the amount perfused per 100 mg dry intestinal weight. Saturable absorption was significantly lower in the vitamin D-deficient group (Jmax 6.9 +/- 1.4 microM X h-1 X 100 mg dry wt-1) than in the vitamin D-replete group (Jmax 13.0 +/- 2.7 microM X h-1 X 100 mg dry wt-1) (P less than 0.05). The presence of aluminum in the perfusion solutions reduced duodenal calcium absorption by 33% (P less than 0.02) in the vitamin D-replete group but not the vitamin D-deficient group. These results suggest that aluminum is absorbed in the duodenum by both a nonsaturable mechanism and a vitamin D-dependent saturable mechanism, for which it may compete with calcium.
Laser-Doppler, H2 clearance, and microsphere estimates of mucosal blood flow
Authors: Kvietys P. R. , Shepherd A. P. , Granger D. N.
Published: December 2017

In autoperfused preparations of feline jejunum, blood flow was measured from the mucosal surface with laser-Doppler velocimetry (LDV) and hydrogen gas (H2) clearance techniques while blood flow was altered by intra-arterial infusions of isoproterenol. LDV and H2 clearance estimates of blood flow were compared with total-wall and mucosal-submucosal blood flows measured with the radiolabeled microsphere technique. Over the range (26.3–73.6 ml X min-1 X 100 g-1) of blood flows attained, a series of direct linear relationships were obtained among LDV, H2 clearance, and microsphere estimates of jejunal blood flow. The slopes of these relationships indicated that the H2 clearance technique over-estimates total intestinal blood flow but reflects mucosal-submucosal flow as measured with microspheres. LDV measurements of blood flow from the mucosal surface were equally well correlated with total and mucosal-submucosal blood flow measured by microspheres, thereby not allowing for a definitive conclusion on the measurement depth of the LDV method. However, the ability of the LDV method to detect changes in blood flow in the perfused gut, even through 3 mm of unperfused tissue, casts a doubt on the assumption that the LDV method has a spatial resolution of less than 0.5–1.0 mm. The results of this study indicate that the H2 clearance technique can be used to measure mucosal blood flow in the small intestine. By contrast, the precise measurement depth of the LDV method is still uncertain and requires further evaluation.
Effects of temperature on ileal blood flow and oxygenation
Authors: Kvietys P. R. , Harper S. L. , Korthuis R. J. , Granger D. N.
Published: December 2017

Arterial pressure, venous outflow pressure, blood flow, and arteriovenous oxygen difference were measured in autoperfused preparations of canine ileum while lumen temperature was altered in 1–5 degrees C increments (or decrements) between 31 and 40 degrees C. Neither blood flow nor vascular resistance was correlated to lumen temperature. However, both arteriovenous oxygen difference and oxygen uptake were linearly correlated with lumen temperature. The relation between ileal oxygen uptake and lumen temperature was consistent with a change in metabolic rate for a 10 degrees C change in temperature (Q10) for oxygen consumption of 2.7. These observations indicate that ambient temperature exerts a profound influence on intestinal oxygen consumption and that variations in temperature may explain the wide range of intestinal oxygen uptake values reported in the literature.
Intracellular electrical activity of muscularis mucosae of the dog stomach
Authors: Morgan K. G. , Angel F. , Schmalz P. F. , Szurszewski J. H.
Published: December 2017

Mechanical and intracellular electrical activity was recorded simultaneously in vitro from smooth muscle of the muscularis mucosae of the canine antrum. The intracellularly recorded membrane potential averaged -51 +/- 1.4 mV (mean +/- SE). Spontaneous electrical activity consisted of spike-shaped potentials that were 20–40 mV in amplitude. The rate of rise of the spike potential was slow (less than 0.2 V/s) and the half-time duration was long (0.5-5.0 s). Phasic contractions were often but not always coupled with spike potentials. Ion substitution studies suggested that the spike potential had a greater dependence on Na+ than on Ca2+. Field stimulation of intramural nerves hyperpolarized the membrane potential and abolished spikes or reduced their amplitude and frequency. These changes were associated with a reduction in tone and phasic contractile activity. The response to stimulation of inhibitory nerves was mimicked by epinephrine, neurotensin, and vasoactive intestinal polypeptide. The resistance to adrenergic blocking agents ruled out the possibility of norepinephrine as the transmitter. The tetrodotoxin sensitivity of the response to neurotensin suggests that neurotensin acts indirectly through the inhibitory nerves. Mimicry between the action of applied vasoactive intestinal polypeptide (VIP) and field stimulation provides support for the hypothesis that VIP may be an inhibitory neurotransmitter. These studies indicate that smooth muscle in the canine gastric muscularis mucosae generates spontaneous electrical and mechanical activity and receives a noncholinergic, nonadrenergic inhibitory innervation.
What transport adaptations enable mammals to absorb sugars and amino acids faster than reptiles?
Authors: Karasov W. H. , Solberg D. H. , Diamond J. M.
Published: December 2017

What digestive adaptations enable mammals to process much more food in much less time with equal or higher digestive efficiency than reptiles and thus to sustain much higher metabolic rates? To answer this question, we measured glucose and proline uptake in small intestinal sleeves of three mammal and three reptile species of similar body size and natural diet. All species exhibit saturable, stereospecific uptake of D-glucose and Na+-dependent L-proline uptake. Passive permeability to glucose is high in hamsters and low in the other species. Uptake increases with temperature up to a maximum around 45–50 degrees C. This temperature dependence may help explain why reptiles bask after meals and why their digestion is impaired if basking is prevented. The total uptake capacity of the small intestine for glucose and proline is seven times higher in mammals than similar-sized reptiles, mainly because the area of mammalian intestine is 4–5.5 times greater. Minor reasons for the higher uptake capacity of mammals are that the transport activity of mammal intestine normalized to quantity of tissue is up to twofold higher and that reptile intestine operates at a lower temperature at night. Vmax for glucose transport varies 10-fold among species, but apparent differences in Km values may be unstirred-layer artifacts. Carrier-mediated uptake of glucose and proline is measurable in the colon of at least three species, but the uptake capacity of the colon is less than 10% of that of the small intestine. An appendix presents a method for measuring the microscopic area of intestines with ridges rather than villi, applies this method to desert iguana intestine, and measures area amplification due to villi in wood rat intestine.
Tone of canine ileocolonic junction: topography and response to phasic contractions
Authors: Quigley E. M. , Phillips S. F. , Cranley B. , Taylor B. M. , Dent J.
Published: December 2017

We wished to define the physiology of the canine ileocolonic sphincter (ICS) and to examine function in relation to the region's anatomy. Prolonged recordings of tone at the ICS were made from seven dogs with isolated ileocolonic loops, and the effects of ileal and colonic distension on sphincteric tone were assessed. In acute experiments, pull-through pressures were measured at the ICS, and the location of the high-pressure zone was related to the region's anatomy. Basal tone at the ICS of approximately 30 cmH2O was confirmed; tone was augmented by colonic and ileal distension. The high-pressure zone was always centered on the anatomic ICS, but it extended into the adjacent ileum and colon for a total length of 2.0 cm (range 1.5–3.0 cm). Phasic contractions contributed to the maintenance of tone at the ICS, and a coordinated pattern of phasic contractions appears to contribute to the sphincteric properties of the region.
Effect of glucagon on hepatic taurocholate uptake: relationship to membrane potential
Authors: Edmondson J. W. , Miller B. A. , Lumeng L.
Published: December 2017

Since glucagon can hyperpolarize hepatic plasma membrane and stimulate biliary bile acid secretion in vitro, we studied the effect of glucagon on taurocholate uptake and its relationship to plasma membrane potential in isolated rat hepatocytes. [14C]taurocholate uptake was linear through 1 min and contained a saturable sodium-dependent and a nonsaturable sodium-independent component. Km of taurocholate uptake by the sodium-dependent system was 18.4 microM. Hill coefficient for Na+ was 2.59 and for taurocholate was 1.1, suggesting that the stoichiometry is 2 Na+:1 bile acid. Stimulation of taurocholate uptake by glucagon was limited to the sodium-dependent component, detected within 5 min of hormone exposure, and was maximum at 30 min. Glucagon, from 10(-8) to 10(-5) M, stimulated taurocholate uptake and hyperpolarized concurrently the plasma membrane potential. Because valinomycin produced a dose-related depolarization of plasma membrane potential, this agent was used to counteract the effects of glucagon. With 10(-6) M glucagon, valinomycin (10(-10) M) depolarized membrane potential from -35.50 to -28.00 mV and inhibited taurocholate uptake from 60% above the control rate to 5% below. These data strongly suggest that taurocholate uptake by isolated hepatocytes is an electrogenic process, and its stimulation by glucagon may be mediated by changes in plasma membrane potential.
Nature of elevated rat intestinal carbohydrase activities after high-carbohydrate diet feeding
Authors: Tsuboi K. K. , Kwong L. K. , Yamada K. , Sunshine P. , Koldovsky O.
Published: December 2017

Adult rats that were maintained on a low-carbohydrate intake showed rapid increase in the activities of sucrase, maltase, and lactase along the length of the small intestine when they were fed a high-starch diet. In the present study, we have identified these activity increases, and showed that they reflect proportional accumulations in enzyme-protein of sucrase-isomaltase (EC 3.2.1.10, 3.2.1.48), maltase-glucoamylase (EC 3.2.1.20), and neutral lactase (EC 3.2.1.23). It was determined that each of these enzymes exists in adult rat intestine in single immunoreactive form and accounts as a group for all sucrase, cellobiase, and most maltase and lactase activities. Dietary change from low to high carbohydrate (starch) resulted in an increase in [3H]leucine accumulation in each of the enzymes, without a change in the amount of label accumulation in total intestinal proteins. The increase in label accumulation in the brush-border carbohydrase pools was matched generally by proportional elevation in the pool concentrations of sucrase-isomaltase and lactase but not maltase. These studies suggest that the elevation of intestinal carbohydrase concentrations induced by high-carbohydrate feeding may involve selective stimulation of their synthesis.
Effects of pentobarbital sodium anesthesia on splanchnic hemodynamics of normal and portal-hypertensive rats
Authors: Lee S. S. , Girod C. , Valla D. , Geoffroy P. , Lebrec D.
Published: December 2017

To determine the effect of pentobarbital sodium anesthesia on the rat with portal hypertension due to portal vein stenosis, four groups of rats were studied. Cardiac output and regional blood flow were measured by radioactive microspheres in anesthetized and conscious sham-operated and portal-hypertensive rats. Anesthesia markedly decreased cardiac output in both sham-operated (109.7 +/- 4.6 vs. 77.8 +/- 1.4 ml/min, P less than 0.001) and portal-hypertensive rats (130.1 +/- 7.6 vs. 93.8 +/- 5.3 ml/min, P less than 0.01). In spite of this diminution in cardiac output, pentobarbital did not significantly change absolute blood flow values of splanchnic organs in either group. However, the fractions of cardiac output perfusing the splanchnic organs were significantly increased by pentobarbital in both groups because of the decrease in cardiac output: sham operated, anesthetized, 22.86 +/- 1.19% vs. conscious, 14.83 +/- 1.02%, P less than 0.001; and portal hypertensive, anesthetized, 26.67 +/- 0.71% vs. conscious, 19.07 +/- 1.44%, P less than 0.001. The hyperdynamic circulation of the portal vein-stenosed rat compared with the sham-operated rat continued to manifest itself with significantly increased portal pressure, cardiac output, and splanchnic blood flow, whether the animal was anesthetized or awake. We conclude that, despite marked hemodynamic changes induced by pentobarbital, the rat with portal vein stenosis remains a useful experimental model of portal hypertension.
Receptors for mammalian tachykinins on isolated intestinal smooth muscle cells
Authors: Souquet J. C. , Grider J. R. , Bitar K. N. , Makhlouf G. M.
Published: December 2017

The existence of receptors for three mammalian tachykinins, substance P (SP), substance K (SK), and neuromedin K (NK), was examined in smooth muscle cells, isolated separately from the longitudinal and circular muscle layers of guinea pig ileum. Tachykinin receptors capable of mediating contraction were present in muscle cells from both layers. The receptors were selectively blocked by the tachykinin antagonist [D-Pro2, D-Trp7,9]substance P but not by muscarinic, gastrin/cholecystokinin, or opiate antagonists (0.3 nM atropine, 1 mM proglumide, and 0.3 nM naloxone, respectively). The rank order of potency of tachykinins in causing contraction, NK greater than SP greater than SK, was similar in both muscle cell types. The results obtained in isolated muscle cells were closely paralleled by results obtained in intact muscle strips; the main difference was the greater sensitivity of isolated cells to tachykinin agonists (250-fold) and antagonist (210-fold). The inhibitory dissociation constant (Ki) of [D-Pro2, D-Trp7,9]substance P estimated from the displacement of dose-response curves (muscle cells) or from Schild plots (muscle strips) differed minimally or not at all, when either SP or SK was used as agonist, consistent with interaction of the two peptides with the same receptor subtype. The notion of a single receptor subtype in ileal muscle cells of the guinea pig was further supported by the occurrence of complete cross-desensitization between SP and SK in muscle strips.
Mechanism and role of intrinsic regulation of hepatic arterial blood flow: hepatic arterial buffer response
Authors: Lautt W. W.
Published: December 2017

Hepatic parenchymal cell metabolic status does not control the hepatic arterial blood flow. Portal blood flow is a major intrinsic regulator of hepatic arterial tone. Hepatic arterial blood flow changes so as to buffer the impact of portal flow alterations on total hepatic blood flow, thus tending to regulate total hepatic flow at a constant level. This response is called the "hepatic arterial buffer response." The mechanism of the arterial buffer response seems to depend on portal blood flow washing away local concentrations of adenosine (production may be constant) from the area of the arterial resistance site. If portal flow decreases, less adenosine is washed away and the local concentration rises resulting in arterial dilation. Putative roles. Hepatic clearance of many hormones and endogenous compounds is blood flow limited. Constancy of total hepatic blood flow is crucial to homeostasis, and severe changes in the magnitude of flow can rapidly alter plasma concentrations of such compounds. The buffer may also prevent portal flow changes from severely altering intrahepatic blood pressures and liver blood volume. Pathological implications. If the O2 supply-to-demand ratio becomes too low, as in the case of a hypermetabolic liver (chronic alcohol exposure), a state of tissue hypoxia can exist without producing hepatic arterial dilation. Therapeutic implications. Livers show protection and improved recovery from several toxic agents, including alcohol, if the O2 supply-to-demand ratio can be increased. Arterial dilation by means of intra-arterial or intra-portal adenosine may prove useful.
Canine gastric emptying of fiber meals: influence of meal viscosity and antroduodenal motility
Authors: Russell J. , Bass P.
Published: December 2017

Dietary fibers such as psyllium and guar gum have been shown to delay the gastric emptying of liquids and solids, presumably due to an increase in meal viscosity. For liquid test meals containing fats, delayed gastric emptying is associated with a reversal of the usual antral-to-duodenal contractile gradient. The present studies were performed to determine whether the gastric emptying of increasingly viscous psyllium and guar gum meals was associated with antroduodenal motility changes. Dogs were surgically fitted with mid-duodenal cannulas for the measurement of gastric emptying. Strain-gauge force transducers were used to monitor antral and duodenal contractile responses to the test meals. Low-viscosity fiber meals emptied from the stomach rapidly (E 1/2 approximately 10 min) compared with the high-viscosity meals (E 1/2 approximately 40 min). None of the test meals stimulated antral or duodenal motility despite differences in gastric emptying time. Other motor parameters such as the time of reappearance and the duration of the burst interval were also unchanged. We conclude a) as test meals' fiber content and viscosity increase, gastric emptying is slowed; and b) viscosity-related delays in gastric emptying are not due to an effect on postprandial antroduodenal motility.
Isolated perfusion of murine liver in situ: technique and validation
Authors: Styne P. N. , Vierling J. M.
Published: December 2017

Although liver perfusion in situ is a valuable technique for the study of hepatic metabolism, it has rarely been applied to the study of mice. This is primarily due to the lack of a simple, reproducible technique to cannulate the delicate portal vein and initiate perfusion without irreversible hepatic injury. Therefore, we developed a technique to overcome these obstacles and performed studies to assess the viability of the perfused murine liver. The inflow catheter assembly permits rapid, reproducible cannulation of the portal vein and protects the cannulated vein from the effects of subsequent manipulations. Serial assessments of perfusion pressure, flow rate, perfusate pH, oxygen consumption, and fluxes of alanine aminotransferase and potassium indicate that the murine liver remains viable during perfusion. Moreover, the light and electron microscopic appearance of perfused livers is indistinguishable from that of freshly excised control livers. This technique should facilitate perfusion studies of hepatic metabolism in murine strains with genetic homogeneity and defined genetic abnormalities of hepatic metabolism.
Cholecystokinin is not a peripheral satiety signal in the dog
Authors: Pappas T. N. , Melendez R. L. , Strah K. M. , Debas H. T.
Published: December 2017

The doses of cholecystokinin (CCK) that have been shown to cause satiety after peripheral administration are pharmacological and whether "physiological" doses of exogenous CCK or endogenously released CCK have a satiety effect is not known. The purpose of the present study is threefold: to compare the potency of endogenous and exogenous CCK for their satiety, cholecystokinetic, and pancreozyminic actions; to determine whether small doses of CCK in the presence of gastric distension cause satiety; and to test the satiety effect of CCK administered centrally into the lateral cerebral ventricle. Dogs were prepared with cerebroventricular guides and esophageal and duodenal fistulas (n = 4), with chronic bile fistulas (n = 8), and chronic pancreatic fistulas (n = 7). Satiety effect was quantified in the esophageal fistula dog by the amount of blenderized food sham fed within 7.5 min. Duodenal perfusion of fat, used as a releaser of endogenous CCK, stimulated pancreatic protein, and gallbladder contraction with D50 values of 1.5 and 0.3 mmol/h, respectively, but had no effect on the volume sham fed (316 +/- 82 ml/min without and 371 +/- 41 ml/min with the maximal dose of sodium oleate infused). The D50 values of CCK-8 (pmol X kg-1 X h-1) for satiety and for stimulation of pancreatic enzyme secretion and gallbladder contraction were 440, 120, and 22, respectively. Injection of CCK-8 into the lateral cerebral ventricle inhibited sham feeding in a dose-dependent manner. We conclude that duodenal fat in doses producing maximal gallbladder and pancreatic stimulation has no satiety effect in the dog.(ABSTRACT TRUNCATED AT 250 WORDS)
Concentration-dependent effects of disulfonic stilbenes on colonic chloride transport
Authors: Smith P. L. , Sullivan S. K. , McCabe R. D.
Published: December 2017

Stripped rabbit colonic mucosa was studied in vitro in Ussing chambers to determine effects of the disulfonic stilbenes 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonate (SITS) and 4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS) and the diuretic furosemide on unidirectional and net Cl fluxes. Results from these studies reveal that SITS (1 mM) added to either the serosal or mucosal bathing solution reduced both unidirectional Cl fluxes with no significant change in net Cl flux. The effects of SITS do not appear to be mediated by an effect on the shunt permeability since SITS (1 mM) did not alter either the intercept or slope of the Na concentration dependence of the serosal-to-mucosal Na flux. Furosemide (1 mM) decreased the serosal-to-mucosal Cl flux without altering short-circuit current (Isc) when added to the luminal bathing solution and reduced both unidirectional fluxes and increased Isc when added to the serosal bathing solution. DIDS (0.5 mM) added to the luminal bathing solution did not alter unidirectional Cl fluxes or Isc. However, serosal addition of DIDS produced dose-dependent changes in Cl transport. At 5 microM DIDS reduced the mucosal-to-serosal Cl flux without altering the serosal-to-mucosal flux or Isc. At 50 microM DIDS reduced the mucosal-to-serosal Cl flux and increased Isc, and at 0.5 mM DIDS increased the serosal-to-mucosal Cl flux, reduced the mucosal-to-serosal Cl flux, and increased Isc and transepithelial conductance. The effect of 0.5 mM DIDS on Isc was reduced by Ca removal from the serosal bathing solution and by the loop diuretics furosemide and bumetanide.(ABSTRACT TRUNCATED AT 250 WORDS)
Cholecystokinin mediates feedback regulation of pancreatic enzyme secretion in rats
Authors: Louie D. S. , May D. , Miller P. , Owyang C.
Published: December 2017

Previous studies have shown that trypsin and chymotrypsin in the duodenum exert a negative-feedback regulation on pancreatic enzyme secretion in the rat. The mechanism responsible for this physiological phenomenon is unknown. By use of a specific and sensitive bioassay based on amylase release from isolated pancreatic acini, the role of cholecystokinin in the negative-feedback regulation of exocrine pancreatic secretion was examined. Rats were prepared with duodenal cannulas and pancreaticobiliary cannulas. Diversion of pancreaticobiliary juice resulted in a threefold increase in pancreatic protein output and an increase of plasma cholecystokinin from a basal level of 0.5 +/- 0.08 pM cholecystokinin octapeptide (CCK-8) to 16 +/- 4 pM CCK-8. Perfusion of trypsin (2 mg/h) or pancreaticobiliary juice returned pancreatic protein output to basal levels and plasma cholecystokinin to 2.1 +/- 1.2 and 0.33 +/- 0.1 pM, respectively. The inhibitory effect of trypsin on cholecystokinin release was enzyme and site specific, since inhibition of cholecystokinin release was not observed with perfusion of amylase into the duodenum or with trypsin into the ileum. Intravenous infusion of proglumide abolished the increase in pancreatic secretion following diversion of pancreaticobiliary juice. Intraduodenal perfusion of lidocaine, infusion of tetrodotoxin into the superior mesenteric artery, or intravenous infusion of atropine inhibited the rise in plasma cholecystokinin seen with diversion of pancreaticobiliary juice. These studies suggest that feedback regulation of pancreatic enzyme secretion in the rat is mediated by release of cholecystokinin. Furthermore, the feedback mechanism is neurally mediated, involving a cholinergic pathway.