bluuebunny/crossref_metadata_2025 huggingface dataset:
Cholesterol metabolism in regenerating liver of the rat
Authors: Field F. J. , Mathur S. N. , LaBrecque D. R.
Published: December 2017

The regenerating rat liver was used as a model to investigate the necessity for new cholesterol synthesis prior to the onset of cell division. Plasma cholesterol levels in partially hepatectomized rats were significantly decreased 24 and 48 h after surgery compared with levels in sham-operated animals. Hepatic cholesteryl ester content was also significantly increased in livers from partially hepatectomized animals, but the hepatic content of unesterified cholesterol was not affected. Hepatic triglyceride content was significantly increased within 6 h after surgery in the regenerating liver. The triglyceride levels reached a peak at 24 h, and by 72 h they had decreased back to levels that were no different from control. In the regenerating liver, microsomal 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase activity was increased 12 h after surgery. The activity of this enzyme remained significantly elevated throughout the 72-h period after surgery. In contrast, 12 h after partial hepatectomy the rate of hepatic cholesterol synthesis was significantly lower than that observed in livers from sham-operated rats. An increase in the rate of cholesterol synthesis was not observed until 48 h after partial hepatectomy, some 32 h after the start of DNA synthesis. Microsomal acyl-CoA:cholesterol acyltransferase activity was unchanged except for a 28% decrease at 72 h after partial hepatectomy. The data suggest that new cholesterol synthesis is not a requirement prior to the initiation of DNA synthesis in the regenerating rat liver.(ABSTRACT TRUNCATED AT 250 WORDS)
Intestinal vasoregulation in spontaneously hypertensive rats
Authors: Granger D. N. , Harper S. L. , Korthuis R. J. , Bohlen H. G. , Kvietys P. R.
Published: December 2017

The intestinal vascular responses to graded reductions in arterial pressure and elevations in venous pressure were measured in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Blood flow and capillary pressure were measured in denervated, autoperfused segments of small intestine. Blood flow, capillary pressure, and total vascular resistance were significantly higher in SHR than WKY at the resting mean arterial pressures. Decrements in arterial pressure led to significant reductions in total vascular resistance in WKY but not in SHR. There was a significant tendency for capillary pressure autoregulation in WKY but not in SHR. Increments in venous pressure did not alter vascular resistance in WKY, yet significantly increased total vascular resistance in SHR. The latter effect was due entirely to a rise in precapillary resistance and is consistent with an enhanced sensitivity of the vasculature to myogenic factors. Intestinal blood flow, measured using 15-micro microspheres, was not significantly different between WKY and SHR in innervated preparations. However, in denervated preparations intestinal blood flow was significantly higher in SHR than WKY, indicating that there is a significant neural component to the increased intestinal vascular resistance in SHR.
Origin and spread of slow waves in canine gastric antral circular muscle
Authors: Bauer A. J. , Publicover N. G. , Sanders K. M.
Published: December 2017

Electrical slow waves recorded from circular muscle cells near the myenteric and submucosal plexuses were found to be significantly different. By measuring the latencies between the arrival of evoked events at two recording sites, slow wave conduction velocities were determined in the three dimensions of circular muscle. Slow waves propagated more rapidly in the axis parallel to the circular fibers than in the axes perpendicular to the circular fibers. The rates of slow wave propagation were also determined in axes parallel and perpendicular to fibers in myenteric and submucosal circular muscles. Slow waves conducted more slowly in the circular muscle near the submucosa than in circular muscle near the myenteric plexus. From conduction velocity measurements, a technique was developed to determine the pacemaker site of spontaneous slow waves in a muscle strip. These data demonstrate that slow waves originate from multiple discrete foci; in muscle strips cut along the long axis of the stomach, these foci are found predominantly in the orad region of the muscle strip; and slow waves originate in the outer myenteric half of the muscle.
Intestinal ion transport and diarrheal disease
Authors: Fondacaro J. D.
Published: December 2017

The physiology of intestinal electrolyte transport is currently an area of intense research interest. Also, reports regularly appear that define possible roles of various endocrine, paracrine, and neurohumoral substances in regulating intestinal ion and water flux. A vast body of knowledge has appeared recently that focuses on the action of specific intracellular mediators or second messengers and certain biochemical events that are thought to be involved in this transport process. This area of research has drawn the attention of the clinical investigator as well as the basic scientist because of the implications of these findings to the understanding of secretory disorders of the gastrointestinal tract, in particular diarrheal disease. The purpose of this review is to focus on recent findings reported in three major areas: the physiology of intestinal electrolyte transport and its regulation; the pathophysiology of secretory diarrhea; and current thoughts and practices in the therapeutic approach to the disease.
Calcitonin gene-related peptide-induced selective inhibition of gastric acid secretion in dogs
Authors: Pappas T. , Debas H. T. , Walsh J. H. , Rivier J. , Tache Y.
Published: December 2017

Calcitonin gene-related peptide (CGRP) is a 37-residue peptide recently characterized in the brain and found in high concentrations in the gut, particularly in the stomach and pancreas. The effects of intravenous infusion of human and rat CGRP (260 pmol . kg-1 . h-1) on gastric secretion and emptying and pancreatic exocrine secretion were studied in conscious dogs. CGRP inhibited by 60-75% gastric acid secretion stimulated by a meal, sham feeding, or step doses of bombesin but did not modify acid response to step doses of histamine or bethanechol. The inhibitory effect of CGRP is not due to blockage of postprandial or bombesin-stimulated gastrin release. CGRP did not influence basal or meal-stimulated pancreatic exocrine secretion or the rate of gastric emptying of a saline meal. These results indicate that CGRP is a potent and selective inhibitor of gastrin-mediated acid secretion in dogs and, under these conditions, did not alter other gastrointestinal functions such as gastric emptying or pancreatic exocrine secretion.
Effect of exocrine pancreatic secretagogues on circulating somatostatin in dogs
Authors: Beglinger C. , Ribes G. , Whitehouse I. , Loubatieres-Mariani M. M. , Grotzinger U. , Gyr K.
Published: December 2017

Several secretagogues of exocrine pancreatic secretion have been proposed to act as regulators of pancreatic D-cell function. To characterize this relationship, we measured incremental responses of protein, bicarbonate, and circulating somatostatin to graded doses of intravenous cholecystokinin (CCK-33), CCK-8, caerulein, bombesin, secretin, and intraduodenally perfused HCl, sodium oleate, and L-phenylalanine in conscious dogs with gastric and pancreatic fistulas and compared them with postprandial values (to a beef meal). Bombesin produced dose-related increases in somatostatin secretion (maximal, 46% of meal response), but caerulein, CCK-33, and CCK-8 released only small amounts of somatostatin at doses equivalent for pancreatic protein secretion. Secretin did not stimulate somatostatin release at any dose studied, whereas intraduodenal HCl at a load submaximal for pancreatic bicarbonate secretion increased somatostatin levels slightly (maximal, 16% of meal response). L-Phenylalanine and sodium oleate markedly increased protein secretion, but only oleate clearly stimulated somatostatin release (maximal, 11% of meal response). Our results suggest a greater quantitative importance of the intestinal phase for exocrine pancreatic stimulation than for somatostatin release.
Inhibitory peptidergic neurons: functional difference between somatostatin and enkephalin in myenteric plexus
Authors: Yau W. M. , Dorsett J. A. , Youther M. L.
Published: December 2017

This study reports on a difference in the inhibitory action of the neuropeptides somatostatin and Met-enkephalin on acetylcholine (ACh) release from myenteric plexus-longitudinal muscle strips of guinea pig small intestine. Met-enkephalin (8.7 X 10(-8) M) inhibited ACh release evoked by either substance P (3.7 X 10(-8) M) or neurotensin (7.5 X 10(-11) M), and this inhibition could be reversed by naloxone (5 X 10(-8) to 5 X 10(-5) M). Neurotensin-induced ACh release was also sensitive to the inhibition by somatostatin. However, when tested in a dose range from 6.1 X 10(-8) to 6.1 X 10(-6) M, somatostatin was ineffective in reducing the efflux of ACh evoked by substance P. These observations provided evidence to support the view that inhibitory peptidergic neurons within the myenteric plexus modulate the activity of cholinergic neurons with a high degree of specificity and that both somatostatin and Met-enkephalin have distinct neuromodulatory functions in the gut.
Cell death (apoptosis) during pancreatic involution after raw soya flour feeding in the rat
Authors: Oates P. S. , Morgan R. G. , Light A. M.
Published: December 2017

Involution of the enlarged pancreas was studied in rats changed from a diet of raw soya flour (RSF) to a normal diet of cubes. After feeding RSF for 4 or 12 wk pancreatic weight, DNA, RNA, and protein were all significantly greater than in control animals fed cubes continuously. When these animals were changed to a cube diet, pancreatic DNA and RNA returned to control values within 48 h, while pancreatic weight and protein reverted to control values within 7 days of the change in diet. The morphological changes seen in the pancreas during involution indicate that cell death occurred by the process of apoptosis. Increased cell death during involution was seen as a rapid increase in the incidence of apoptotic bodies (AB) located in the cytoplasm of intact acinar cells and macrophages. These AB's contained condensed fragments of cytoplasm, nuclear, or a combination of these remnants, which were derived from the acinar cell. The increase in apoptosis after withdrawal of the RSF diet was probably in response to the withdrawal of the trophic influence, cholecystokinin.
In vitro effects of beta-casomorphins on ion transport in rabbit ileum
Authors: Hautefeuille M. , Brantl V. , Dumontier A. M. , Desjeux J. F.
Published: December 2017

beta-Casomorphins (beta-CM) represent opioid peptides derived from bovine beta-casein. As opiates are known to decrease short-circuit current (Isc) and stimulate intestinal electrolyte absorption, we tested the effects of natural beta-CM-4-OH, beta-CM-5-OH, and three related analogues on electrolyte transport in rabbit ileum in vitro. At concentrations of 10(-7) to 10(-3) M, the three analogues (beta-[D-Ala2]CM-4-NH2, beta-[D-Ala2,Met5]CM-5-NH2, and beta-[D-Ala2,4,Tyr5]CM-5-NH2) caused a dose-dependent, naloxone-reversible reduction in Isc after addition to the serosal side of the preparation. beta-[D-Ala2,4,Tyr5]CM-5-NH2 also decreased Isc after mucosal addition. Serosal addition of the same analogue stimulated absorption of sodium and chloride (+2.90 +/- 0.95 and +2.12 +/- 0.60 mu eq . h-1 . cm-2, respectively) and inhibited residual flux (-1.80 +/- 0.57 mu eq . h-1 . cm-2). The natural beta-CM tested did not decrease Isc. These results demonstrate that beta-CM analogues stimulate intestinal absorption of electrolytes by an opioid mechanism. The fact that beta-[D-Ala2,4,Tyr5]CM-5-NH2 was effective on the mucosal side favored the hypothesis that certain food-related opioid peptides might be absorbed by the intestine.
Pharmacological characterization of opossum distal colonic muscularis mucosae in vitro
Authors: Percy W. H. , Christensen J.
Published: December 2017

In muscularis mucosae from the opossum distal colon, both tone and spontaneous contractions were highly dependent on the available oxygen. Acetylcholine and histamine caused, respectively, atropine- and pyrilamine-sensitive contractions. Norepinephrine relaxed the tissue, an effect abolished by propranolol. Under these conditions norepinephrine failed to elicit contractions and at higher concentrations again caused relaxations. The tissue gave concentration-dependent relaxations to ATP but not to ADP, AMP, or adenosine. Electrical field stimulation (20-30 Hz, 1-2 ms, 120 mA) revealed a cholinergic excitatory innervation and a nonadrenergic, noncholinergic neural inhibition. Cholecystokinin, gastrin, substance P, and vasoactive intestinal polypeptide were without effect on this tissue. In these respects, colonic muscularis mucosae differs considerably from that of other gastrointestinal viscera.
Absorption of pantothenic acid in rat and chick intestine
Authors: Fenstermacher D. K. , Rose R. C.
Published: December 2017

Pantothenic acid absorption was evaluated in the intestine of rat and chicken to reevaluate the concept that this nutrient crosses the mucosa by simple diffusion. Unidirectional influx of [3H]pantothenic acid (0.9 microM) across the brush-border membrane of rat jejunum in vitro demonstrates sodium dependence and saturation kinetics. Net transepithelial transport (absorption) of pantothenic acid takes place in everted sacs of jejunum against an electrochemical potential gradient. This accumulation does not occur in tissue exposed to metabolic inhibitors. Also, pantothenic acid accumulates in the transport cells of both rat and chicken intestine against a 9- to 10-fold concentration gradient. Recently absorbed pantothenic acid is freely diffusible from isolated chicken enterocytes. No metabolic conversion of pantothenic acid was detected during absorption in the intestine of either species under conditions in vitro or in vivo. The present results indicate that pantothenic acid present at low concentrations is absorbed in the intestine by a specific transport mechanism; the process is best described as sodium-dependent, secondary active transport.
Centrally mediated stimulation of jejunal water and electrolyte secretion by calcitonin in dogs
Authors: Primi M. P. , Bueno L.
Published: December 2017

The effects of intracerebroventricular versus intravenous injection of salmon calcitonin (sCT) at a dose of 0.2 IU X kg-1 on jejunal fluxes of water, Na+, and K+ were investigated before and after vagotomy or an intravenous treatment with indomethacin (1 mg X kg-1) in dogs prepared with a jejunal Thiry-Vella loop. Intestinal transport in the Thiry-Vella loop and concomitant mean transit time were measured during an infusion (2 ml X min-1) of an isotonic electrolyte solution and phenol red bolus injections. Basal net water absorption was significantly (P less than 0.01) reduced by 51.7% from 2 to 3 h after intracerebroventricular administration of sCT, Na+ absorption was reduced by 62.6%, and net flux of K+ was reversed from absorption to secretion. A similar intravenous dose had no effect. Previous treatment with indomethacin or bilateral thoracic vagotomy did not reduce the water, Na+, and K+ secretory effects of centrally administered sCT, whereas indomethacin per se appeared to reduce water and electrolyte absorption. A significant (P less than or equal to 0.05) increase in mean transit time was observed after intracerebroventricular but not intravenous calcitonin (0.2 IU X kg-1), and this effect was abolished after vagotomy. These results suggest that calcitonin may be involved in the central control of intestinal secretion in dog, inasmuch as these effects were mediated by different structures from those affecting intestinal motility.
Glucose-coupled sodium absorption in the developing rat colon
Authors: Potter G. D. , Burlingame S. M.
Published: December 2017

The developing mammalian colon is lined by villi and is capable of glucose and amino acid absorption at birth in the rat. Neither the point at which this capacity is lost nor the effect of the capacity for glucose transport on Na absorption has been studied. We have now applied a system for perfusion of the lumen of in vitro segments of colon from 20-day-old fetal rats, and pups between 6 and 8 days old, to measure Na transport and transepithelial potential difference (PD). The lumens of colons from animals at both ages were perfused with solutions containing glucose or mannitol and 22Na. Net Na transport was 164 +/- 37 mu eq X h-1 X g dry weight tissue perfused-1, as determined by the difference between lumen-to-bath and bath-to-lumen flux in fetal rat colons at day 20. Glucose increased the lumen-to-bath flux by 90 +/- 35 mu eq X h-1 X g-1. PD was immediately increased from -1.7 +/- 0.16 to -8.0 +/- 0.96 mV (lumen with respect to bath) by the addition of glucose, and the change in PD was inhibited by 10(-4) M phlorizin. The PD response to glucose was lost at day 2 of life, but the villus epithelium persisted. Amiloride, 10(-4) M, did not alter PD or Na transport at either age. We conclude that the fetal rat colon exhibits glucose-dependent Na flux at birth but that this property is lost by 6-8 days.(ABSTRACT TRUNCATED AT 250 WORDS)
Source of activator calcium in isolated guinea pig and human gastric muscle cells
Authors: Bitar K. N. , Burgess G. M. , Putney J. W. , Makhlouf G. M.
Published: December 2017

The source of Ca2+ responsible for contraction was examined in suspensions of smooth muscle cells and in perfused single muscle cells from guinea pig and human stomach. In both preparations removal of Ca2+ from the medium or addition of the Ca2+ channel blocker methoxyverapamil had no effect on the contractile response to various agonists, including cholecystokinin octapeptide (CCK-8) and acetylcholine, but inhibited the response to high extracellular K+ by 76-82%. Repeated stimulation of guinea pig or human single muscle cells in Ca2+-free medium, or in the presence of methoxyverapamil caused a progressive decrease and eventual abolition of contractile response; response was restored on restitution of Ca2+ to the medium or elimination of methoxyverapamil. Measurement of 45Ca2+ content in guinea pig muscle cells showed that CCK-8 had no effect on the rate of Ca2+ influx but increased the rate of Ca2+ efflux transiently by sixfold. Net peak efflux coincided with the time of peak contraction and was stoichiometrically related to the degree of contraction. Equipotent, maximally effective contractile doses of CCK-8, acetylcholine, and methionine-enkephalin caused equivalent degrees of net Ca2+ efflux. The results indicate that contractile agonists cause release of Ca2+ from a depletable intracellular store in gastric muscle cells. The release is accompanied by a dose-dependent increase in Ca2+ efflux and is capable of sustaining an initial maximal contraction. Repeated contractile activity requires influx of Ca2+ from extracellular sources.
Enterohepatic circulation of bile acids in pigs: diurnal pattern and effect of a reentrant biliary fistula
Authors: Legrand-Defretin V. , Juste C. , Corring T. , Rerat A.
Published: December 2017

The present studies were undertaken 1) to assess the quantitative absorption of total bile acids in the portal vein of normally fed, unanesthetized pigs with an intact biliary tract and 2) to evaluate the effect of a chronic reentrant biliary fistula on absorption. In the intact biliary tract group (5 pigs), mean total bile acid concentration averaged 83.9 +/- 2.0 and 15.6 +/- 0.6 microM in portal and arterial blood, respectively, and 216.9 +/- 20.4 mmol of total bile acids were absorbed over 24 h. Time courses of blood concentration and absorption were described all along the light-dark cycle, and hepatic uptake averaged 79.3 +/- 0.5%. A reentrant choledocal fistula in the upper duodenum (5 pigs) did not affect mean daily blood concentrations (87.5 +/- 2.4 and 19.1 +/- 0.8 microM in portal and arterial blood, respectively), daily absorption (226.4 +/- 23.7 mmol, i.e., 93.5% of the daily secretion), or hepatic uptake (76.4 +/- 1.1%), but it did seem to influence the daily kinetics of blood concentration and absorption. These studies supply quantitative and kinetic data about the absorptive stage of the enterohepatic cycle in pigs and show that a bile fistula is suitable for the study of biliary dynamics.
Colonic formation of soft feces in rabbits: a role for endogenous prostaglandins
Authors: Pairet M. , Bouyssou T. , Ruckebusch Y.
Published: December 2017

Rabbits produce hard and soft feces in a circadian rhythm. The motor activity of the haustrated proximal colon is inhibited during the formation of soft feces, whereas the spiking activity of the distal colon is stimulated. A potential role for endogenous prostaglandins (PG) in the control of the soft-feces elaboration by the rabbit colon was investigated in conscious animals by using PGE2 and PGF2 alpha and by inhibiting them with indomethacin. The infusion of both PGE2 and PGF2 alpha induced typical electromechanical events consisting of inhibition of the proximal and stimulation of the distal colon and was followed by soft-pellet defecation. Rabbits accustomed to be fed twice daily produced soft feces at fixed intervals of 252 +/- 32 min after the evening meal, with a soft-to-hard feces ratio of 1.45. After indomethacin treatment, this ratio was significantly (P less than 0.01) reduced to 0.92. These results are consistent with the concept that endogenous prostaglandins play a major role in the motor function involved in soft-feces formation by the rabbit.
Role of substance P nerves in longitudinal smooth muscle contractions of the esophagus
Authors: Crist J. , Gidda J. , Goyal R. K.
Published: December 2017

Longitudinal muscle strips from different sites along the opossum esophagus were stimulated transmurally so as to produce neurally mediated contractions. Low-frequency transmural stimulation produced contractions after termination of the stimulus ("off" contractions), whereas high-frequency stimuli produced contractions beginning during the stimulus and extending beyond termination of the stimulus (extended-duration contractions). The intrastimulus portion of the extended-duration contraction was partially antagonized by atropine or substance P desensitization, whereas the poststimulus portion of the contraction was selectively and fully antagonized by desensitization with substance P. A combination of atropine and substance P desensitization abolished the extended-duration contraction. The amplitude of contraction was greater in the proximal than in the distal strips, irrespective of the mode of stimulation. The poststimulus portion of the extended-duration contraction was significantly longer in muscle strips taken from more distal than proximal portions of the esophagus. This gradient in duration of contractions was abolished by substance P desensitization but was not affected by atropine. Exogenously applied substance P (10 microM) produced equally sustained long-duration contractions at all sites along the esophagus. These observations suggest that a) both acetylcholine- and substance P-containing nerves are responsible for the extended-duration contraction of longitudinal muscle, and b) transmural stimulation causes an aborally directed increase in the duration of contractions; this gradient of increasing duration of contraction appears to be due to a more prolonged neural release of substance P at more distal sites.
Regulation of neurotensin release from canine enteric primary cell cultures
Authors: Barber D. L. , Buchan A. M. , Walsh J. H. , Soll A. H.
Published: December 2017

A recently developed primary cell-culture system allows direct study of the cellular mechanisms regulating neurotensin secretion from intestinal mucosal cells. We now report the use of these methods to evaluate the modulation of neurotensin release by adrenergic, cholinergic, and peptidergic transmitters. Collagenase-dispersed canine ileal mucosal cells, enriched for neurotensinlike immunoreactivity (NTLI) by centrifugal elutriation, were maintained for 48 h on collagen-coated culture dishes. Epinephrine (0.01-100 microM) stimulated a dose-dependent increase increase in NTLI secretion. The NTLI response to epinephrine increase in NTLI secretion. The NTLI response to epinephrine was competitively inhibited by propranolol, producing a parallel rightward shift of the epinephrine dose-response curve. alpha-Adrenergic agonist methoxamine (10 microM) and clonidine (10 microM) did not alter basal NTLI secretion. Epinephrine stimulation was not significantly inhibited by the alpha-adrenergic antagonists prazosin (10 microM) or yohimbine (10 microM). The diterpene forskolin, an adenyl cyclase activator, increased NTLI release and had an additive effect on the response to epinephrine. In contrast to beta-adrenergic activation, carbachol and somatostatin produced a dose-dependent inhibition of epinephrine-stimulated NTLI release. At 100 microM carbachol, NTLI release was inhibited 68%, and this action was partially blocked by atropine (0.1 microM). Somatostatin (100 nM) produced a 96% inhibition that was not surmountable by 1 mM epinephrine. These data indicate that neurotensin release is stimulated by beta-adrenergic agonists and adenylate cyclase activation. Somatostatin and the muscarinic agonist carbachol directly inhibit NTLI release.
Action of cholecystokinin analogues on exocrine and endocrine rat pancreas
Authors: Otsuki M. , Okabayashi Y. , Ohki A. , Oka T. , Fujii M. , Nakamura T. , Sugiura N. , Yanaihara N. , Baba S.
Published: December 2017

In the present study we have examined the abilities of cholecystokinin-(26-33)-amide [CCK-(26-33)-NH2, CCK-8], nonsulfated CCK-(26-33)-NH2 (desulfated CCK-8), CCK-(30-33)-NH2 (CCK-4), CCK-(26-33)-OH (deamidated CCK-8), and succinyl CCK-(27-31)-NH2 (Suc-Des-Asp6,Phe7-CCK-7) to stimulate exocrine pancreatic secretion from both isolated pancreatic acini and isolated perfused pancreas. We have also compared this action with their ability to cause insulin release. The modification of either the N- or C-terminal amino acid residues of CCK-8 decreased in potency, but the magnitude of the stimulation of enzyme secretion caused by a maximally effective peptide concentration was the same. The minimal effective concentration of CCK-8, desulfated CCK-8, and CCK-4 for insulin release from the isolated rat pancreas in the presence of 8.3 mM glucose was the same as that for pancreatic exocrine secretion. In contrast, the concentrations of deamidated CCK-8 and Suc-Des-Asp6,Phe7-CCK-7 required to produce insulin release were 5-10 times higher than those required to cause stimulation of pancreatic enzyme and juice secretion. It is concluded therefore that the N-terminal 4-amino acid residues or the C-terminal 2-amino acid residues of CCK-8 are not essential for biological activity but do contribute to its potency. In addition, the C-terminal 2-amino acid residues and an amide group in the C-terminal phenylalanine residue of CCK-8 appear to be important determinants of the insulin-releasing activity of the CCK peptides.
Intestinal anaphylaxis in the rat: jejunal response to in vitro antigen exposure
Authors: Perdue M. H. , Gall D. G.
Published: December 2017

In previous studies we showed that rats sensitized to egg albumin respond to in vivo intraluminal antigen with decreased net absorption of Na+, Cl-, and water. These abnormalities are associated with high serum levels of immunoglobulin E (IgE) antibodies and mucosal mast cell degranulation. In the present in vitro study electrical parameters, unidirectional fluxes of Na+ and Cl-, and levels of cAMP were determined in jejunum from sensitized and control rats during a basal period and after antigen addition. In Ussing chambers potential difference and short-circuit current increased significantly in tissue from sensitized rats after addition of 100 micrograms/ml of egg albumin to both mucosal and serosal surfaces. These changes were accompanied by a reversal of net Cl- absorption to net Cl- secretion. The presence of doxantrazole, a mast cell-stabilizing agent, in the buffer prevented these abnormalities. No changes occurred in response to antigen challenge in tissue from controls. In a further series of experiments the antigen was added only to the mucosal side of the tissue in Ussing chambers. In these studies short-circuit current increased after a lag period of approximately 25 min and was significantly increased (P less than 0.025) at 35 min. cAMP levels increased significantly in jejunal slices from sensitized rats exposed to antigen for 2 min. Our findings suggest that the in vivo transport abnormalities induced by IgE-mediated mucosal reactions to a food protein are related to antigen stimulation of a Cl- secretory process.
Pancreatic acinar cells in monolayer culture: direct trophic effects of caerulein in vitro
Authors: Logsdon C. D. , Williams J. A.
Published: December 2017

Adult mouse pancreatic acinar cells were cultured as monolayers on collagen gels. Cells plated in medium containing 10% fetal bovine serum (FBS), epidermal growth factor (1 nM), carbachol (1 microM), insulin (1 microM), and corticosterone (10 nM) showed adaptive and growth responses. An adaptive phase occurred over the first 4-5 days, during which there was an approximately 50% decrease in the content of protein and DNA in the cultures, and the remaining attached cells showed reduced contents of zymogen granules. Subsequently, the cells spread out, divided, and formed confluent monolayers by days 11-14. Cell division was indicated by a doubling of the content of protein and DNA between days 5 and 9 and a 13-fold increase in thymidine incorporation. Microscopic examination of 14-day cultures revealed monolayers of cuboidal cells with morphological features of pancreatic acinar cells. To determine the direct effects of cholecystokinin on pancreatic acinar cell growth, cells were cultivated in media lacking added hormones and containing only 2.5% FBS with or without caerulein, a cholecystokinin analogue. Caerulein led to a 152% increase in DNA and an 89% increase in protein at day 9. By use of a preincubation [3H]thymidine incorporation assay, caerulein induced a dose-dependent increase in [3H]thymidine incorporation and nuclear labeling index, which was detectable at 0.1 nM, one-half maximal at 1 nM, and a maximal threefold increase occurred at 10 nM concentration. The results demonstrate a direct effect of caerulein on the pancreas to induce cell growth.
Intestinal sugar transport: does the Na+ gradient provide all the energy?
Authors: Baker R. D.
Published: December 2017

It has not yet been established that the energy released from the Na+ gradient during Na+-sugar cotransport by small intestine is sufficient, by itself, to drive uphill sugar transport under conditions in which other sources of energy are available and in which sugar is being vigorously transported. This work attempts to test the thermodynamic sufficiency of the Na+ mechanism under such conditions using hamster jejunum in vitro. From data on tissue uptake of D-galactose and unstirred layer considerations, the concentration ratio for galactose across the apical membrane during mucosal-to-serosal galactose transport was estimated to be at least 50 when concentration in the bulk mucosal solution was 2.2 mM. This estimate and reasonable assumptions regarding intracellular Na+ activity and apical membrane potential were used to calculate the minimum physiological coupling ratio (i.e., the ratio of coupled net fluxes of Na+ and galactose) required if all the energy necessary for galactose transport is transferred from Na+. The minimum physiological coupling ratio required was roughly 1.4. An estimate based on the ratio of transepithelial chord permeabilities to galactose, instead of the apical concentration ratio, would be higher. The measured physiological coupling ratio (0.4) was considerably less than that required. For reasons discussed, this result should be interpreted with caution. It can be concluded that the issue of energetic adequacy is not yet settled.
Active K+ absorption by the gastric mucosa: inhibition by omeprazole
Authors: Reenstra W. W. , Bettencourt J. D. , Forte J. G.
Published: December 2017

Unidirectional fluxes of K+ across the histamine-stimulated frog gastric mucosa bathed in Cl(-)-Ringer were measured. Comparison of nutrient-to-secretory and secretory-to-nutrient K+ fluxes determined using either 42K or 86Rb as radioisotopic tracers gave identical results, and thus either isotope could be used for K+ flux measurements; the majority of these experiments used 86Rb as the tracer. Short-circuited mucosas maintained a small net absorption of 0.07 +/- 0.03 mueq X cm-2 X h-1 (n = 9). Omeprazole decreased acid secretion from 4.98 +/- 0.58 to 0.08 +/- 0.02 mueq X cm-2 X h-1 and reversed the direction of net K+ flux giving a net secretion of 0.09 +/- 0.04 mueq X cm-2 X h-1. Ouabain increased the rate of K+ absorption to 0.32 +/- 0.08 mueq X cm-2 X h-1 with a flux ratio (JKn----s/JKs----n) of 0.31 +/- 0.09; subsequent addition of omeprazole significantly decreased the rate of K+ absorption and increased the flux ratio. Omeprazole did not alter the fraction of transmucosal current carried by either K+ or Cl-. For omeprazole inhibited-mucosas at open circuit increasing the secretory osmolarity by 100 mosM with sucrose decreased the transmucosal resistance by 14% and increased nutrient-to-secretory K+ flux by 31%. For actively secreting mucosas no significant changes were seen in either parameter. These results are shown to be consistent with an electroneutral apical H+-K+ exchange pump and diffusion from the gland lumen-to-the secretory fluid, being rate limiting for K+ flux.
Seasonal fluctuations in pepsinogen secretion from frog esophageal peptic glands
Authors: Shirakawa T. , Hirschowitz B. I.
Published: December 2017

The seasonal activity of pepsinogen secretion in the Rana catesbeiana was studied by use of peptic gland bearing esophageal mucosa mounted in a perfused double chamber. The amount of the basal pepsinogen secretion during hibernation (winter) and breeding (spring) periods was approximately 25 and 55% of basal secretion during the active (summer) period. The circumannual variation of basal secretion was highly correlated (r = 0.88, n = 37) with the pepsinogen content of the mucosa. The fractional rate of basal secretion (approximately 2% of content per hour) remained essentially constant, and pepsinogen as a fraction of total protein remained at between 20 and 25%. The results indicate that the decrease in absolute basal secretion from frog peptic glands during winter is a consequence of decreased content and hence synthesis of protein, including pepsinogen, by the mucosa. In addition, stimulated secretory responses to both bethanechol and bombesin, as a multiple of basal rate, were reduced during both hibernation and breeding periods, whereas the response to isoproterenol was entirely abolished during the hibernation period. By contrast, the secretory response to isobutylmethylxanthine remained constant (approximately 200% of basal) through all seasons, suggesting that mechanisms responsible for enzyme translocation and secretion remained intact. Reduced basal and secretagogue-stimulated secretion during hibernation and breeding seasons is thus likely due to a combination of reduced protein synthesis and decreased number or function of agonist receptors in peptic cells of the frog.
Importance of interstitial matrix hydration in intestinal chylomicron transport
Authors: Tso P. , Barrowman J. A. , Granger D. N.
Published: December 2017

We have shown previously that lymph flow has a profound effect on intestinal chylomicron transport. However, since lymph flow both determines the rate of convective movement of chylomicrons within the interstitium and reflects the degree of hydration of the interstitial matrix, we were unable to determine which factor was more important for the inverse relation between the chylomicron appearance time and lymph flow. In this investigation, we measured the chylomicron appearance time in rats with a normal lymph flow and expanded matrix (study A), in rats with a reduced lymph flow but expanded matrix (study B), and finally in rats with a dehydrated matrix (study C). The chylomicron appearance times were 11.7, 13.6, and 21.7 min for the rats from studies A-C, respectively. Thus, the data obtained from this study indicate that the matrix hydration may exert a more significant influence on chylomicron movement than lymph flow per se. In conclusion, the reduced chylomicron appearance time produced by expansion of the mucosal interstitium results from a diminished resistance of the interstitial matrix to chylomicron movement rather than a decreased transit time due to an enhanced convective flux of chylomicrons.
Vagal control of canine postprandial upper gastrointestinal motility
Authors: Hall K. E. , el-Sharkawy T. Y. , Diamant N. E.
Published: December 2017

The role of the vagus nerves in the control of postprandial motility in the upper gastrointestinal tract was investigated in four dogs by use of a bilateral cervical cooling blockade technique. On administration of food, the fasting migrating motor complex (MMC) was replaced by the postprandial (feeding) pattern. Feeding pattern duration varied in a dose-dependent manner with either total volume or calories of food. During the feeding pattern, oscillations in lower esophageal sphincter (LES) pressure occurred at time intervals equivalent to the MMC cycle period. Twenty-one control feeding experiments and 17 postprandial vagal blockade experiments were performed, with a minimum of three of each type in each dog. Vagal blockade, initiated at times ranging from 15 min to 4 h after feeding and maintained for up to 5 h, abolished the postprandial activity in the upper gastrointestinal tract. During postprandial vagal blockade, LES pressure was abolished and bursts of contractions were observed only in the upper small bowel, a pattern resembling that observed during vagal blockade in the fasted state. These bursts occurred at the expected times relative to, and their cycle period was not significantly different from, that of the MMCs recorded prior to feeding. Vagal blockade started prior to feeding prevented initiation of the fed pattern, which appeared immediately on termination of the blockade. We conclude that initiation and maintenance of the postprandial pattern in the upper gastrointestinal tract with concurrent inhibition of the fasting MMC normally require vagal integrity. The "clock" controlling the MMC cycle period is not reset by feeding, but its effect on motility is suppressed.
Effect of systemic acid-base disorders on ileal intracellular pH and ion transport
Authors: Wagner J. D. , Kurtin P. , Charney A. N.
Published: December 2017

We previously reported that changes in ileal net Na absorption correlated with arterial pH, changes in net HCO3 secretion correlated with the plasma HCO3 concentration, and changes in net Cl absorption correlated with arterial CO2 partial pressure (PCO2) during the systemic acid-base disorders. To determine whether changes in intracellular pH (pHi) and HCO3 concentration [( HCO3]i) mediated these effects, we measured pHi and calculated [HCO3]i in the distal ileal mucosa of anesthetized, mechanically ventilated Sprague-Dawley rats using 5,5-[14C]dimethyloxazolidine-2,4,-dione and [3H]inulin. Rats were studied during normocapnia, acute respiratory acidosis, and alkalosis, and uncompensated and pH-compensated acute metabolic acidosis and alkalosis. When animals in all groups were considered, mucosal pHi was not altered, but there were strong correlations between mucosal [HCO3]i and both arterial PCO2 (r = 0.97) and [HCO3] (r = 0.61). When we considered the rates of ileal electrolyte transport that characterized these acid-base disorders [A. N. Charney and L.P. Haskell, Am. J. Physiol. 245 (Gastrointest. Liver Physiol. 8): G230-G235, 1983], we found strong correlations between mucosal [HCO3]i and both net Cl absorption (r = 0.88) and net HCO3 secretion (r = 0.82). These findings suggest that the systemic acid-base disorders do not affect ileal mucosal pHi but do alter mucosal [HCO3]i as a consequence of altered arterial PCO2 and [HCO3]. The effects of these disorders on ileal net Cl absorption and HCO3 secretion may be mediated by changes in [HCO3]i. Arterial pH does not appear to alter ileal Na absorption through changes in the mucosal acid-base milieu.
Morphological and biochemical changes of the pancreas in rats treated with acetaldehyde
Authors: Majumdar A. P. , Vesenka G. D. , Dubick M. A. , Yu G. S. , DeMorrow J. M. , Geokas M. C.
Published: December 2017

Daily intraperitoneal injections of acetaldehyde for 10 days to adult rats produced distinct morphological and biochemical changes in the exocrine pancreas, without affecting the body weight, pancreatic weight, and DNA, RNA, and protein content of the pancreas. By electronmicroscopy, although the number and size of the acinar zymogen granules appeared to be the same between the saline- and acetaldehyde-treated rats, the zymogen granules of the latter group showed decreased osmiophilia. Acinar mitochondria of the acetaldehyde-treated rats were found to be slightly swollen with dense granules, and plasma membrane fragments were often seen in the acinar lumen. Administration of acetaldehyde significantly decreased immunoreactive cationic trypsin (ogen) and total amylase activity in the pancreas, but not in the serum, where amylase activity was markedly increased. Basal secretion of amylase, trypsinogen, and chymotrypsinogen from isolated dispersed pancreatic acini of acetaldehyde-treated rats was increased by 40-50%. Nicotine (5-25 mM) induced a profound increase in secretion of the same enzymes from isolated acini of both saline- and acetaldehyde-treated rats, but in the latter group there was a concomitant rise in LDH release. Furthermore, CCK-8 (1 nM), secretin (1 microM), and carbachol (10 microM) either alone or in combination with nicotine (12.5 mM) produced a profound stimulation in amylase, trypsinogen, and chymotrypsinogen secretion from acini of both groups of rats. On the other hand, secretion of 3H-pulse-labeled proteins from isolated acini of acetaldehyde-treated rats by nicotine was decreased by approximately 50% compared with the controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Only free bile acid drives ileal absorption of taurocholate
Authors: Luxon B. A. , King P. D. , Forker E. L.
Published: December 2017

We compared the intestinal absorption of monomeric taurocholate bound to albumin with the absorption of the free form. In the presence of albumin the apparent uptake coefficient is about three times greater than that in its absence. This result resembles the one reported previously for the liver. In the gut, however, this phenomenon is attributable to the diffusive resistance of an unstirred intervillous fluid layer, whereas in the liver this explanation has been excluded. We conclude that only free taurocholate engages the bile acid transport system in ileal mucosa, whereas in the liver bile acid uptake is driven by albumin-taurocholate complexes, as well as by free taurocholate.
Effects of calcium antagonist TMB-8 on active Na and Cl transport in rabbit ileum
Authors: Donowitz M. , Cusolito S. , Sharp G. W.
Published: December 2017

The effects of 3,4,5-trimethoxybenzoate 8-(N,N-diethylamino)octyl ester (TMB-8), an agent that traps calcium within intracellular stores, were studied on active electrolyte transport in rabbit ileum under basal conditions and after altering transport by increasing the intracellular cAMP content or by exposure to two agonists that act by altering intracellular Ca2+ (carbachol and serotonin). TMB-8 decreased the ileal short-circuit current and increased active Na and Cl absorption by increasing the mucosal-to-serosal Na and Cl fluxes. These effects were reversed by increasing the bathing solution Ca2+ to 4 mM, a concentration that itself did not alter basal ileal transport. The maximum glucose- and amino acid (alanine)-induced increase in Na absorption in the ileum was not affected by TMB-8. The effects on basal transport of TMB-8 were not associated with a change in 45Ca2+ entry across the ileal serosal surface. TMB-8 did not alter cAMP-induced secretion, as judged by its lack of effect on the increase in short-circuit current caused by 8-bromo-cAMP (10(-4) M). TMB-8 totally prevented the transport effects of carbachol but did not inhibit the effects of serotonin. These data suggest a role for intracellular Ca2+ in regulation of basal ileal Na and Cl transport but not in cAMP-induced secretion. There appear to be several pools of intracellular Ca2+ involved in neurohumoral effects on active electrolyte transport.
Contributions of ischemia and reperfusion to mucosal lesion formation
Authors: Parks D. A. , Granger D. N.
Published: December 2017

Two theories have been proposed to account for the mucosal injury associated with intestinal ischemia, hypoxia-countercurrent exchange, and oxygen free radicals. The countercurrent mechanism suggests that mucosal injury should occur predominately during the ischemic period, whereas the oxygen free radical hypothesis predicts that the majority of mucosal injury results from reperfusion of ischemic tissue. Histological specimens obtained during the ischemic period and following reperfusion allowed a systematic evaluation of the time course of development of mucosal lesions in a regional ischemia model. Reperfusion after 3 h of regional hypotension reduced mean mucosal thickness from 1,022.2 +/- 6.3 to 503.6 +/- 10.0 microns. The decrease in mucosal thickness was largely due to a reduction in villus height, inasmuch as the reduction in crypt depth was statistically insignificant. A significantly smaller change in mucosal thickness was observed when the bowel was subjected to 3 h ischemia without reperfusion. The mucosal injury produced by 3 h ischemia and 1 h reperfusion was more severe than that produced by 4 h ischemia without reperfusion. The results of this study suggest that most of the tissue damage produced by the widely employed regional hypotension model occurs at the time of reperfusion.
Measurement of resistance to flow across antroduodenal area during fasting
Authors: Mearin F. , Azpiroz F. , Malagelada J. R.
Published: December 2017

Changes in antroduodenal resistance to flow may participate in the regulation of gastric emptying and duodenogastric reflux. Little is known, however, about the relationship between antroduodenal resistance and the physiological patterns of contractile activity in this area. We have developed an instrument that maintains an electronically regulated constant-pressure gradient of 2 mmHg across both ends of a flaccid cylinder positioned fluoroscopically across the pylorus. Because resistance bears a constant inverse relationship to flow at a fixed pressure gradient, changes in the recorded rate of airflow through the cylinder are a measure of antroduodenal resistance. In vitro studies showed that, under these conditions, airflow was a function of the diameter and length of the air path and the frequency and duration of external pressure waves greater than 2 mmHg. In vivo studies in four dogs examined the relationship between interdigestive phases of motor activity and variations in resistance exerted by the antroduodenal area. We found that flow rates varied markedly with each phase. Antroduodenal resistance was lowest during motor quiescence (phase I), rose gradually during irregular activity (phase II), and reached its peak during maximal contractile activity (phase III) (P less than 0.05). Resistance was similar for antegrade and retrograde flow. Additional studies suggested that the pyloric area contributes mostly to resistance during phase I, whereas duodenal resistance at least matches that of the pylorus during phase III.