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PubMed2006

Mucosal stimulation activates secretomotor neurons via long myenteric pathways in guinea pig ileum.

This study examined whether mucosal stimulation activates long secretomotor neural reflexes and, if so, how they are organized. The submucosa of in vitro full thickness guinea pig ileal preparations was exposed in the distal portion and intracellular recordings were obtained from electrophysiologically identified secretomotor neurons. Axons in the intact mucosa of the oral segment were stimulated by a large bipolar stimulating electrode. In control preparations, a single stimulus pulse evoked a fast excitatory postsynaptic potential (EPSP) in 86% of neurons located 0.7-1.0 cm anal to the stimulus site. A stimulus train evoked multiple fast EPSPs, but slow EPSPs were not observed. To examine whether mucosal stimulation specifically activated mucosal sensory nerve terminals, the mucosa/submucosa was severed from the underlying layers and repositioned. In these preparations, fast EPSPs could not be elicited in 89% of cells. Superfusion with phorbol dibutyrate enhanced excitability of sensory neurons and pressure-pulse application of serotonin to the mucosa increased the fast EPSPs evoked by mucosal stimulation, providing further evidence that sensory neurons were involved. To determine whether these reflexes projected through the myenteric plexus, this plexus was surgically lesioned between the stimulus site and the impaled neuron. No fast EPSPs were recorded in these preparations following mucosal stimulation whereas lesioning the submucosal plexus had no effect. These results demonstrate that mucosal stimulation triggers a long myenteric pathway that activates submucosal secretomotor neurons. This pathway projects in parallel with motor and vasodilator reflexes, and this common pathway may enable coordination of intestinal secretion, blood flow, and motility.

Action Potentials↗
PubMed1995

The humoral immune system in coeliac disease.

IgA is transported into intestinal secretions to perform exclusion of luminal antigens. The prerequisites are antigen sampling by the Peyer's patch M cells, antigen processing by antigen-presenting cells, and presentation of antigenic peptides by HLA class II molecules to immunocompetent T-cells. The basis for intestinal immunity is the maturation cycle of specifically primed T and B cells from the gut-associated lymphoid tissue via mesenteric lymph nodes and peripheral blood back to the intestinal lamina propria. In coeliac disease, patients are sensitized against gluten and serum gliadin antibodies are often detected. Gliadin antibodies are also found in other gastrointestinal diseases, other disorders and in healthy individuals not carrying the coeliac disease-specific DQA/DQB alleles. On the other hand, serum reticulin and endomysium autoantibodies are both sensitive and highly disease-specific. Positivity in patients with normal jejunal morphology indicates latency of coeliac disease. These tissue autoantibodies are directed against fibroblast-derived extracellular matrix proteins. The immune system is involved in the amplification and perpetuation of the abnormalities of the intestinal mucosa in coeliac disease. The role of antibody in the pathogenesis remains unknown. The author hypothesizes gluten-triggered autoimmune mechanism to be operative.

Antibody Formation↗
PubMed1978

The role of IgA immunoglobulins in the passive transfer of protection to Taenia taeniaeformis in the mouse.

Normal mice were protected against infection with metacestodes of Taenia taeniaeformis when administered intestinal, colostral or serum immunoglobulins obtained from adult mice previously orally infected with the parasitie. The protective capacity of these preparations was found to be associated mainly with IgA of colostrum and intestinal secretions and IgG of serum. The removal of IgA and IgG from immune colostrum and serum, respectively, abolished the protective effect. Neonatal mice were protected against infection with T. taeniaeformis when fed purified colostral IgA and serum IgG from immune donors. The intraduodenal injection of intestinal IgA from immune donors into 4-week-old mice passively protected the recipients against infection with T. taeniaeformis, but intestinal IgG from immune donors had no protective effect when given in this manner. The protective capacity of IgA and IgG was largely eliminated by prior absorption with T. taeniaeformis antigen or hatched, activated oncospheres of T. taeniaeformis.

Animals↗
PubMed1991

Dissociation between systemic and mucosal humoral immune responses in coeliac disease.

We examined humoral immunity in coeliac disease as expressed in serum (systemic immunity), and in saliva, jejunal aspirate, and whole gut lavage fluid (mucosal immunity). The aims were to define features of the secretory immune response (IgA and IgM concentrations and antibody values to gliadin and other food proteins measured by enzyme linked immunosorbent assay (ELISA)) in active disease and remission, and to establish whether secretions obtained by relatively non-invasive techniques (saliva and gut lavage fluid) can be used for indirect measurements of events in the jejunum. Serum, saliva, and jejunal aspirate from 26 adults with untreated coeliac disease, 22 treated patients, and 28 immunologically normal control subjects were studied, together with intestinal secretions obtained by gut lavage from 15 untreated and 19 treated patients with coeliac disease and 25 control subjects. Jejunal aspirate IgA and IgM and gut lavage fluid IgM concentrations were significantly raised in patients with untreated coeliac disease; the lavage fluid IgM concentration remained higher in patients with treated coeliac disease than in controls. Serum and salivary immunoglobulin concentrations were similar in the three groups. Patients with untreated coeliac disease had higher values of antibodies to gliadin compared with treated patients and control subjects in all body fluids tested; these were predominantly of IgA and IgG classes in serum, and of IgA and IgM classes in jejunal aspirate and gut lavage fluid. Values of salivary IgA antibodies to gliadin were significantly higher in untreated coeliacs, though antibody values were generally low, with a large overlap between coeliac disease patients and control subjects. In treated patients, with proved histological recovery on gluten free diet, serum IgA antigliadin antibody values fell to control values, though serum IgG antigliadin antibody values remained moderately raised. In contrast, there was persistence of secretory antigliadin antibodies in treated patients (particularly IgM antibody) in both jejunal aspirate and gut lavage fluid. Antibody responses to betalactoglobulin and ovalbumin were similar to those for gliadin, including persistence of high intestinal antibody values in patients with treated coeliac disease. There was a positive correlation between antibody values in jejunal aspirate and gut lavage fluid, but not between saliva and jejunal aspirate; thus salivary antibodies do not reflect intestinal humoral immunity.

Adolescent↗
PubMed1981

Studies on hydragogue drugs: effect of surfactants on cAMP levels in the rat jejunal mucosa in short time experiments in vivo.

Theophylline and the surface active agents specified below were instilled into the jejunum of anaesthetized rats, and the cAMP levels in the mucosal tissue determined after 71/2 and 15 min. incubation in vivo. Most experiments were done in rats prepared with two tied intestinal loops; one of these served as the control loop and the other as the stimulated loop. The surfactants (mmol/l) included dodecylsulphate (17), dioctylsulphosuccinate (5.6), cetrimonium bromide (4.1), deoxycholic acid (2.4 and 3.6) and Lubrol WX (0.5% w/v). Theophylline (10 mmol/l) caused a substantial increase in cAMP (110% +/- 17, n = 7 and 60% +/- 8.9, n = 10, respectively) and dodecylsulphate a minor and transitory increase (28.1% +/- 3.8, n = 10 and 11.7% +/- 4.9, n = 8). The other agents were without stimulatory effect on cAMP, although like dodecylsulphate they may significantly affect normal intestinal cation and glucose transport under these conditions. The results, therefore, do not suggest that stimulation of cAMP and intestinal secretion induced thereby is any significant phenomenon in the overall hydragogue effect of these agents, at least not in short term jejunal experiments.

Animals↗
PubMed1998

The absence of stereoselective P-glycoprotein-mediated transport of R/S-verapamil across the rat jejunum.

We have studied the potential stereoselective transport and metabolism of R/S-verapamil in rat jejunum, in-situ. A regional single-pass perfusion of the rat jejunum was performed on 24 rats in six separate groups. The effective permeability (Peff) was assessed for three different concentrations of verapamil, 4, 40 and 400 mg L(-1). The Peff of each enantiomer was also determined at 400 mg L(-1) when chlorpromazine (10 mM) was added to the perfusion solution. Two other groups of rats received R/S-verapamil as an intravenous infusion and the intestinal secretion and metabolism were studied by simultaneously perfusing the jejunum with a control or with chlorpromazine (10 mM) added. The concentrations in the outlet perfusate of each enantiomer of verapamil and norverapamil were assayed with HPLC. R/S-Verapamil is a high permeability drug in the proximal rat small intestine throughout the luminal concentration range studied and complete intestinal absorption was expected. There was an increase of Peff from 0.42 x 10(-4) cm s(-1) to 0.80 x 10(-4) cm s(-1) (P < 0.05) at concentrations from 4 to 400 mg L(-1), respectively. The observed concentration-dependent jejunal Peff and fraction absorbed (P < 0.05) of R/S-verapamil is consistent with the saturation of an efflux mechanism. When chlorpromazine (a P-glycoprotein inhibitor/substrate) was added the jejunal Peff increased to 1.47 x 10(-4) cm s(-1). There was no difference between the Peff of the two enantiomers in any of these experiments. The efflux of R/S-norverapamil into the rat jejunum was high after intravenous administration of R/S-verapamil, suggesting extensive metabolism in the enterocyte. In conclusion, both R/S-verapamil enantiomers are P-glycoprotein substrates, but there is no stereoselective transport of R/S-verapamil in the rat jejunum. The results also suggests that R/S-norverapamil is formed inside the enterocytes.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2002

Transport mechanisms of nicotine across the human intestinal epithelial cell line Caco-2.

Ulcerative colitis is a disease more commonly seen in nonsmokers. Because nicotine was postulated to be a beneficial component of tobacco smoke for ulcerative colitis, various formulations of nicotine have been developed to improve the local bioavailability within the gastrointestinal tissue. In the present study, to characterize the disposition of nicotine in the intestines, we investigated intestinal nicotine transport using Caco-2 cells. Nicotine was predominantly transported across Caco-2 cell monolayers in a unidirectional mode, corresponding to intestinal secretion, by pH-dependent specific transport systems. The specific uptake systems appear to be distinct from organic cation transporters and the transport system for tertiary amines, in terms of its substrate specificity and the pattern of the interaction. These transport systems could play a role in the intestinal accumulation of nicotine from plasma and could also be responsible for the topical delivery of nicotine for ulcerative colitis therapy. These findings could provide useful information for the design of effective nicotine delivery.

Biological Transport↗
PubMed1992

Binding of Pseudomonas cepacia to normal human intestinal mucin and respiratory mucin from patients with cystic fibrosis.

Although not as prevalent as Pseudomonas aeruginosa, Pseudomonas cepacia is another opportunistic pathogen which colonizes the lungs of at least some patients with cystic fibrosis. A subgroup of these patients exhibits the "cepacia syndrome", i.e., a rapid clinical deterioration and death within one year. To investigate potential early sites of bacterial attachment, we have measured the specific binding of P. cepacia isolates from cystic fibrosis (CF) sputa to both CF and non-CF mucins purified from respiratory and intestinal secretions, respectively. As shown in microtiter binding assays, clinical isolates from 19/22 patients were found to bind to both mucins, with the highest specific binding exhibited by isolates from eight patients, seven of whom later died with the cepacia syndrome. No differences were observed in the binding capacity of the two (CF versus non-CF) mucins. Binding was specific, saturable, and not influenced by tetramethylurea, a disruptor of hydrophobic associations. Individual sugars were ineffective as hapten inhibitors, as were several lectins. Mucins treated by reduction/alkylation or chloroform/methanol extraction showed enhanced bacterial binding, findings which were attributed to exposure of underlying binding sites. Deglycosylation procedures indicated that mucin receptors for P. cepacia include N-acetylglucosamine and N-acetylgalactosamine, probably linked together as part of core oligosaccharide structures. P. cepacia isolates also bound to buccal epithelial cells, and mucin partially inhibited the binding of those isolates of P. cepacia that also had the ability to bind to mucin. We speculate that specific binding of P. cepacia to secreted mucins may be an early step in the pathogenesis of the cepacia syndrome.

Bacterial Adhesion↗
PubMed1996

Experimental studies of intestinal ion and water transport.

A major advance in transport physiology was H. H. Ussing's development of the voltage-clamp method, and later the Koefoed-Johnsen-Ussing model for Na+ transport. In the same decade, J. C. Skou identified the Na(+)-K(+)-ATPase, which maintains the Na+ and K+ gradients that drive most epithelial transport processes. With this foundation, Danish scientists have pursued the mechanism of ion transport and the resulting solute-linked water flow. Recent contributions have been on isosmotic transport, suggesting solute recycling, and KCl-water cotransport in the basolateral epithelial cell membrane. Efficient small intestinal nutrient absorption is dependent on coupling to the Na+ gradient. Cotransport of Na+ and glucose is quantitatively the most important absorptive mechanism in the small intestine, as illustrated by the success of oral rehydration solutions in diarrhoea. The majority of amino acids are likewise transported by Na+ dependent carriers, but recent experiments have identified a concomitant Cl- dependency for some. Regulation of intestinal secretion, both under normal digestive processes, and in response to enterotoxins, has turned out to be very complex. It involves local and central neuronal regulation through an array of neurotransmitters and local actions of gastrointestinal hormones. Major effectors are the submucosal neurons and the main transmitters serotonin, vasoactive intestinal peptide, acetylcholine, substance P, and neurotensin. Development of antisecretagogues is impeded by the existence of several receptor subtypes and significant species differences. The Na+ and water-conserving properties of the large intestine have been shown to be regulated by adrenocortical hormones, with aldosterone as a potent stimulator of colonic Na+ absorption. A major colonic function is the symbiosis with the anaerobic bacterial population. The fermentation of carbohydrate to short-chain fatty acids, which can be absorbed, supplements small intestinal digestive function.

Animals↗
PubMed2004

Uroguanylin and guanylin peptides: pharmacology and experimental therapeutics.

Guanylin, uroguanylin, and the bacterial heat-stable enterotoxin (ST) peptides comprise a new family of cyclic guanosine 3'-5' monophosphate (cGMP)-regulating agonists. The discovery of guanylin and uroguanylin peptides stems from studies of cellular mechanisms underlying a form of secretory diarrhea caused by enteric bacteria. Guanylin, uroguanylin, and microbial ST peptides activate a common apical membrane receptor-guanylate cyclase (R-GC) that elicits large increases in the intestinal secretion of chloride and bicarbonate via the intracellular second messenger, cGMP. Guanylin and uroguanylin were isolated from rat jejunum and opossum urine, respectively. These peptides are endogenous peptide hormones that physiologically regulate R-GC signaling proteins in target cells. Physiological roles for these peptides include the regulation of epithelial cell balance in the intestinal epithelium and modulation of sodium balance through actions in the kidney. The guanylin-uroguanylin-ST peptides are candidate therapeutic agents targeting receptors in the intestine, kidney, and other epithelia. For example, uroguanylin has anti-tumor actions in an animal model for human colon cancer. The ST peptides can be used as diagnostic agents to detect secondary colon cancers by single photon-emitting computed tomography (SPECT) imaging, thus localizing metastatic forms of colon cancer. Other examples of potential therapeutic applications for the guanylin family of cGMP-regulating agonists are: (1) the irritable bowel syndrome (IBS) with constipation, (2) salt-dependent forms of high blood pressure, (3) liver regeneration and repair, and (4) respiratory diseases such as asthma. Competitive pharmacological antagonists of bacterial ST peptides offer a means for treating the diarrhea caused by ST-secreting strains of enteric bacteria.

Amino Acid Sequence↗
PubMed2004

Lateral intercellular space volume as a determinant of CFTR-mediated anion secretion across small intestinal mucosa.

Studies of full-thickness, small intestinal preparations have shown that maximal anion secretion [indexed by short-circuit current (I(sc))] during intracellular cAMP (cAMP(i)) stimulation is transient and followed by a decline toward baseline. Declining I(sc) is preceded by decreases in transepithelial conductance (G(t)), which in the small intestine reflects the lateral intercellular space (LIS) volume of the paracellular pathway. We hypothesized that decreases in LIS volume limit the magnitude and duration of cAMP(i)-stimulated anion secretion. Experimental manipulations to increase the patency of the LIS (assessed by G(t) and electron microscopy) were investigated for an effect on the magnitude of cAMP(i)-stimulated anion secretion (assessed by the I(sc) and isotopic fluxes) across murine small intestine. In control studies, changes of G(t) after cAMP(i) stimulation were associated with a morphological "collapse" of the LIS, which did not occur in intestine of CFTR-null mice. Removal of the outer intestinal musculature, exposure to a serosal hypertonic solution, or increased serosal hydrostatic pressure minimized reductions in G(t) and increased the cAMP(i)-stimulated I(sc) response. Increased I(sc) primarily resulted from increased Cl(-) secretion that was largely bumetanide sensitive. However, bumetanide-insensitive I(sc) was also increased, and similar increases occurred in the Na(+)-K(+)-2Cl(-) cotransporter (NKCC1)-null intestine, indicating that activities of non-NKCC1 anion uptake proteins are also affected by LIS volume. Thus LIS patency is an important determinant of the magnitude and duration of CFTR-mediated anion secretion in murine small intestine. Decreases in LIS volume may limit the pool of available anions to basolateral transporters involved in transepithelial secretion.

Animals↗
PubMed2006

Strobilocercus fasciolaris infection with hepatic sarcoma and gastroenteropathy in a Wistar colony.

Tapeworm cysts were identified in liver of Wistar rats and it induced fibrosarcoma in liver and gastroenteropathy in stomach and intestine. The tapeworm larva was confirmed as Strobilocercus fasciolaris by PCR linked mitochondrial DNA sequencing. Light microscopy, special staining (masson trichrome) and immunoflouresence supported the diagnosis of fibrosarcoma. Infiltration of plasma cells, macrophages and eosinophils were observed in the liver section. Gastric mucosal hyperplasia, dilation of gastric glands with secretion, intestinal mucosal cell hyperplasia, proliferation of duodenal submucosal glands were confirmed by light microscopy and supported by PAS, AB staining. The concomitant development of hepatic sarcoma and gastroenteropathy by larvae of Taenia taeniaeformis (S. fasciolaris) infection is very rare and is the first reported case in Wistar rats to our knowledge.

Animals↗
PubMed1994

Regulation of cholecystokinin synthesis and secretion in rat intestine.

Cholecystokinin is a classical gastrointestinal hormone that is produced by discrete endocrine cells of the upper small intestine. Cholecystokinin is produced in various molecular forms that result from differences in posttranslation processing of a single gene product. Cholecystokinin is secreted from the intestine in response to the ingestion of food. We observed that specific dietary substances increase the rate of transcription of the cholecystokinin gene and stimulate cholecystokinin release in rats. In contrast the paracrine transmitter, somatostatin, inhibits dietary-stimulated cholecystokinin secretion and lowers intestinal mRNA levels. Evidence that cholecystokinin gene expression is not necessarily linked to hormone secretion is supported by the observation that the neuropeptide, bombesin, stimulates cholecystokinin release but does not modify intestinal cholecystokinin mRNA levels. To examine the intracellular messengers that might regulate the cholecystokinin cell directly, we developed an in vitro method for studying cholecystokinin release from isolated intestinal mucosal cells. In this perifusion system, cholecystokinin release was stimulated by membrane depolarizing concentrations of KCl (50 mmol/L), the calcium ionophore A23187 (1 mumol/L), and the cAMP analogue dibutyryl cAMP (1 mumol/L). Biologically active cholecystokinin was also released in a dose-dependent manner by the peptide transmitters, bombesin and monitor peptide. These findings indicate that neurotransmitters and hormones may directly regulate the cholecystokinin cell and suggest that the phosphoinositide and adenylate cyclase cascades mediate stimulated-cholecystokinin secretion.

Animals↗
PubMed1992

Affinity purification of functional receptors for Escherichia coli heat-stable enterotoxin from rat intestine.

Active receptors for Escherichia coli heat-stable enterotoxin (ST) were partially purified by ligand-affinity chromatography. The affinity column was prepared by coupling ST to biotin derivatized with an extended N-hydroxysuccinylated spacer arm prior to binding to monomeric avidin immobilized on agarose. Detergent extracts of rat intestinal mucosa membranes were quantitatively depleted of ST binding activity when chromatographed on this affinity matrix. Biotinylated ST-receptor complexes were eluted from affinity columns with 2 mM biotin and these complexes quantitatively dissociated with bile salts. Using this technique, functional ST receptors were purified maximally about 2000-fold, with about 3% of the total activity in crude extracts recovered in these purified preparations. Analysis of affinity-purified preparations by polyacrylamide gel electrophoresis and silver staining demonstrated a major protein subunit of 74 kDa. Affinity cross-linking of these preparations to 125I-ST demonstrated specific labeling predominantly of the 74-kDa subunit. In addition, lower amounts of labeled ST were incorporated into subunits of 164 and 45 kDa, confirming the heterogeneous nature of ST receptors. Purified receptors bound ST in a concentration-dependent fashion, with an IC50 of 10(-9) M. These studies demonstrate that ligand-affinity chromatography can be employed to purify ST receptors. The availability of purified receptors will facilitate further studies of mechanisms underlying ST-induced intestinal secretion.

Animals↗
PubMed2002

Neuropathophysiology of irritable bowel syndrome.

Widespread symptoms associated with the irritable bowel syndrome (IBS) are abnormal defecation and abdominal pain, both of which can be exacerbated by psychogenic stress. Disordered defecation may present as diarrhea or constipation. A subgroup of IBS patients alternate from one to the other over time. Urgency to stool often accompanies the diarrheal-state, and patients with the constipation-predominant form of IBS report straining and the feeling of incomplete evacuation. Basic scientific research aims for improved understanding of the physiology and pathophysiology of the digestive systems from which the arrays of IBS symptoms emerge. The key systems for the defecation-related symptoms are the intestinal secretory glands, the musculature, and the nervous system that controls and integrates their activity. Abdominal pain and discomfort arising from these systems adds the dimension of sensory neurophysiology. This review details current concepts of the underlying pathophysiology in terms of the physiology of intestinal secretion, motility, nervous control, sensing function, immuno-neural communication, and the brain-gut axis.

Abdominal Pain↗
PubMed2002

Development of antigen induced colitis in SCID mice reconstituted with spleen derived memory type CD4(+) CD45RB(+) T cells.

BACKGROUND AND AIMS: Enteric bacterial and/or food antigens may be crucial in the development of colitis but little is known of the exact mechanism of antigen specific reactions in this condition. The aim of this study was to determine whether systemically primed antigen specific CD4(+) T cells containing both CD45RB(high) and CD45RB(low) populations participate as a pathogenic subset that in turn leads to inflammatory reactions selectively in the large intestine. METHODS: SCID mice were reconstituted with splenic CD4(+) CD45RB(+) T cells or CD4(+) CD45RB(low) T cells isolated from donor mice systemically primed with ovalbumin (OVA) plus CFA. The reconstituted mice were then fed OVA for several weeks. RESULTS: Reconstitution of SCID mice with OVA primed splenic CD4(+) T cells, containing populations of CD45RB(high) and CD45RB(low), resulted in the development of colitis by 4-5 weeks following repeated administration of oral OVA. Histopathological study revealed thickened wall, inflammatory cell infiltration, crypt elongation, and loss of goblet cells in the large intestine. The CD4(+) CD45RB(low) population of cells extracted from the affected large intestine secreted high levels of interferon gamma (IFN-gamma) and tumour necrosis factor alpha (TNF-alpha) at the protein and mRNA levels. Administration of neutralising antibodies to TNF-alpha, but not to IFN-gamma, prevented the development of colitis. Furthermore, adoptive transfer with OVA primed splenic CD4(+) CD45RB(low) T cells evoked severe colitis. CONCLUSIONS: These results demonstrate that systemically primed activated/memory CD4(+) CD45RB(low) T cells can mediate the development of specific antigen induced colitis in SCID mice, and also that TNF-alpha is critical in the induction of this type of colitis. Our results contrast with those from studies in some colitis models in which CD45RB(low) T cells appeared to prevent colitis through secretion of immunosuppressive cytokines.

Adoptive Transfer↗
PubMed1983

Stimulation of prostaglandin production in rabbit ileal mucosa by bradykinin.

When rabbit ileal mucosa was incubated with exogenous [3H]arachidonic acid (AA), its major metabolites, identified by comigration with known standards on thin-layer chromatography, were prostaglandin (PG) E2, 6-keto-PGF1 alpha and to a lesser extent PGF2 alpha and PGD2. The rate of prostanoid release from the serosal surface of the mucosa only was increased after incubation th either bradykinin, lys-bradykinin, melittin or the calcium ionophore A 23187, in a rapid and dose-dependent fashion. Peptide concentrations as low as 10(-9) M were effective. Kinin-induced release of AA or its metabolites required the presence of Ca++ in the incubation medium. Stimulation of prostanoid release by lys-bradykinin was completely blocked by indomethacin. The combined lipoxygenase/cyclooxygenase inhibitors BW 755 and eicosa-5,8,11,14-tetraynoic acid and the lipoxygenase inhibitor nordihydroguaiaretic acid also blocked the stimulation of PG synthesis by lys-bradykinin. These inhibitors caused an increase in levels of AA released from the tissue by lys-bradykinin. The phospholipase inhibitors, mepacrine and U- 10029, inhibited the lys-bradykinin-stimulated release of both prostanoids and AA. At higher concentrations, U- 10029 inhibited the stimulation of transepithelial potential difference and short-circuit current across rabbit ileal mucosa produced by lys-bradykinin. These results support the hypothesis that bradykinin-stimulated intestinal secretion may be mediated by PGs.

Animals↗
PubMed2004

Role of dietary intake and intestinal absorption of oxalate in calcium stone formation.

The factors affecting the urinary excretion of oxalate are critical to the risk of forming calcium oxalate stones. This article reviews the role of dietary and intestinal oxalate in determining the level of oxalate excreted in urine. The amount of oxalate available for absorption throughout the intestine is highly dependent on the state of oxalate (a) in the food ingested, and (b) in the intestinal contents at each section of the intestinal tract since only the soluble form of oxalate can be absorbed. In this respect, the solubility of calcium oxalate (CaOx) under the prevailing conditions is paramount in determining the amount of oxalate available for absorption at any particular site. In turn, the main factors that control how much oxalate is in the soluble form are pH and the concentrations of calcium, magnesium and (indirectly) phosphate. Based on these parameters, a model of the intestine has been constructed which brings together the available evidence on the prevailing concentrations of these various factors at different sites in the intestine after allowing for dietary intake and the concentration of the above ions in intestinal secretions. The model then calculates the likely concentration of oxalate that is in the soluble form at each site and therefore available for passive absorption at that site. The model shows that oxalate is likely to be absorbed in the stomach, although it can be also absorbed in the small intestine, particularly at the distal end (after the absorption of calcium), and in the colon, since, on a normal intake of calcium and phosphate, most of the calcium in the large bowel would be anticipated to be precipitated as calcium phosphate under the prevailing alkaline conditions and high concentration of phosphate. The amount of free oxalate in the colon is also controlled by the presence or absence of Oxalobacter formigenes, an anaerobe that has an obligate requirement for oxalate as a source of energy and cellular carbon.

Animals↗