Intestinal Water Transport Research Articles

Analysis of antidiarrhoeic effect of plants used in popular medicine

People customarily use the extracts of plants known to have antidiarrhoeal effects without any scientific base to explain the action of the extract. For this reason, an investigation was undertaken with a view to determining the efficacy of the effects of the brute aqueous extract (BAE) of the leaves of Psidium guajava (guava), Stachytarpheta cayenensis (bastard vervain), Polygonum punctatum (water smartweed), Eugenia uniflora (Brazil or Surinam cherry) and Aster squamatus (zé-da-silva) on the intestinal transport of water in rats and on the gastrointestinal propulsion in mice. With the exception of the BAE of S. cayenensis, all other BAE's have increased the absorption of water in one or more intestinal portion in relation to the control group. All tested BAE, except that of P. punctatum, reduced the gastrointestinal propulsion in relation to that of the control group. The results indicate that the BAE of the leaves of P. guajava, S. cayenensis, P. punctatum, E. uniflora and A. squamatus have a potential antidiarrhoeic effect to be confirmed by additional investigations in animals infected with enteropathogenic agents.

Effects of cerebral TRH on intestinal water transport: role of vagal, muscarinic, and VIP pathways

Thyrotropin-releasing hormone (TRH) is a central nervous system (CNS) transmitter that stimulates various gastrointestinal secretory and motor processes by increasing vagal outflow. In this study, the CNS effects of TRH on ileal and jejunal water transport were examined in awake rats and dogs, respectively. Cerebral but not intravenous TRH (0.1-5.0 nmol/kg) significantly (P < 0.01) reversed net water absorption from approximately 30 microliters.cm-1.h-1 in rats and 300 microliters.cm-1.h-1 in dogs toward net water secretion of 60 and 600 microliters.cm-1.h-1, respectively. Truncal vagotomy and ganglionic blockade with chlorisondamine completely abolished this stimulatory effect of cerebral TRH, whereas adrenalectomy, hypophysectomy, noradrenergic and opiate blockade, and inhibition of prostaglandin and nitric oxide synthesis did not. Atropine methylnitrate significantly (P < 0.05) attenuated the stimulatory response produced by TRH by approximately 30%. Intravenous infusion of the vasoactive intestinal peptide (VIP) receptor antagonist, [4Cl-D-Phe6, Leu17]VIP (0.05-5.0 mumol.kg-1.h-1), significantly (P < 0.01) inhibited the stimulatory response of TRH by approximately 60%. Pretreatment of the animals with both atropine and the VIP antagonist completely abolished ileal and jejunal water secretion stimulated by cerebral TRH. These results indicate that 1) TRH acts within the CNS to stimulate net ileal and jejunal water secretion in rats and dogs, respectively; 2) these actions are mediated by vagal pathways; and 3) stimulation of intestinal secretion by cerebral TRH is primarily mediated by a VIP-sensitive mechanism and, in part, by a muscarinic mechanism.

Guanylin: a peptide regulator of epithelial transport 1

Regulation of intestinal salt and water transport is critical to the maintenance of fluid volume. Control of this life-sustaining activity is mediated by the concerted actions of hormones, neurotransmitters, and locally acting factors. The intestinal peptide guanylin is ideally suited to play a pivotal role in this regulation. Guanylin is produced by the epithelium and appears to be secreted mucosally to act locally on an apical receptor. The guanylin receptor is a member of the guanylate cyclase (GC-C) family of proteins. Elevation of intracellular cyclic GMP by guanylin mediates the stimulation of Cl- secretion, which results in the increased intestinal fluid secretion. Proguanylin is found in the circulation and GC-C occurs in other epithelia, suggesting that guanylin plays an endocrine role by regulating the function of tissues such as the kidney and liver. Uroguanylin is a structurally related peptide that is abundant in urine, has biological activity similar to guanylin, and appears to be made by the intestine. This peptide may link the intestine and kidney in an endocrine pathway for control of renal salt excretion. Overproduction of guanylin/uroguanylin would be expected to elicit secretory diarrhea similar to that caused by the bacteria that produce peptide analogs of these endogenous peptide hormones. This unique molecular mimicry has provided clues leading to the discovery of guanylin and insight into the mechanism of action of these intestinal peptides. The discoveries of guanylin and uroguanylin have provided exciting opportunities for further enhancing our understanding of epithelial transport and function.

Amino Acids Mediate Postprandial Jejunal Proabsorption

Ingestion of a meal stimulates small intestinal ion and water transport. Current evidence suggests that this response, termed proabsorption, is primarily mediated by the apical Na+/glucose cotransporter. Like glucose, the majority of amino acid absorption occurs by Na+-dependent, secondary active transport. The purpose of this study was to determine the role of amino acid transport in meal-induced jejunal ion and water absorption in vivo. Exteriorized, neurovascularly intact jejunal loops measuring 25 cm were created in six female mongrel dogs, and the dogs were allowed to recover for 2 weeks. After an overnight fast, the loops were perfused with a standard buffer containing 10 mM aspartate, leucine, glycine, or lysine. Net water and electrolyte absorption before and after a mixed meal was calculated using [14C]polyethylene glycol as a volume marker. Aspartic acid, leucine, glycine, and lysine are each transported by a separate transporter system. Except for lysine, each amino acid significantly (P < 0.05) potentiated sodium and water absorption after a meal. In addition, this effect was at least as great as that seen with 10 mM glucose. These results demonstrate that amino acid transporter, like the Na+/glucose cotransporter, mediates meal-induced jejunal sodium and water absorption and may be as important in the proabsorptive response.

Concentrations of antisecretory factor in eggs and in chicken blood plasma.

1. In the present study, the concentration of antisecretory factor (ASF), a lectin with hormone-like properties, and with the capacity to regulate water and electrolyte transport in the small intestine, was higher in hen's egg yolk than in egg white (1.20 v. 0.46 units/ml). 2. The blood plasma concentrations of ASF activity were higher in d-old chicks (1.03 units/ml) than in 7-d-old (0.42 units/ml) or 21-d-old birds (0.18 units/ml); the contents were found to be high again in 35-d-old chickens, but to have decreased by 60 to 90% after transport to slaughter 1 day later. 3. The amount of ASF activity was lower in two groups of chickens manifesting patent loose droppings at slaughter (0.15 units/ml in one group, and 0.08 units/ml in the other), than in two groups with normal faecal consistency (0.65 units/ml in one group, and 0.72 units/ml in the other). 4. The results demonstrate the presence of ASF in eggs, and a variation of ASF activity in chickens blood plasma in relation to age, stress and faecal consistency. The interpretation of these data suggests a regulatory influence of ASF on chicken intestinal transport of water.

Interleukin 1 induces a neurally mediated colonic secretion in rats: Involvement of mast cells and prostaglandins

Background/Aims: Interleukin 1β (IL-1β) is known to regulate intestinal ion and water transport in vitro through prostaglandin release. This study investigated the effect of IL-1β on colonic net water flux in vivo to determine its nature (nerve mediation versus action on the epithelium), the mediators involved, and its relationship with mast cell degranulation. Methods: Isolated colonic loops of anesthetized animals were infused with Ringer's buffer containing [14C]polyethylene glycol 4000. Net water flux was calculated according to 14C activity determined in the effluent collected at 15-minute intervals. Histological analysis was used to identify intact mast cells in colonic sections and radioimmunoassay to determine histamine levels. Results: Both IL-1β and the calcium ionophore A23187 induced colonic hypersecretion during 30 minutes. This effect was blocked by tetrodotoxin, doxantrazole, and indomethacin but not chlorpheniramine. Recombinant human interleukin 1β decreased the number of intact mast cells. This effect was eliminated by doxantrazole but not tetrodotoxin or indomethacin. A23187 or IL-1β increased histamine levels in the effluent during 75 and 45 minutes, respectively. Conclusions: In vivo, rhL-1β induces colonic hypersecretion in rats. This effect is nerve mediated but not H1 receptor mediated and involves mast cell degranulation and prostaglandin release.

Water and electrolyte absorption and secretion

Intestinal water and electrolyte transport mechanisms continue to be characterized in increasing depth. This review deals principally with the modulation of these processes. In particular, there is continuing interest in the effects of luminal contents on intestinal function in both normal and disease states. Various aspects of extrinsic and intrinsic neural control have been investigated by several groups whose findings are discussed.

5-HT Receptor Subtypes Involved in Luminal Serotonin-Induced Secretion in Rat Intestine in Vivo

The purpose of this study was to compare the 5-hydroxytryptamine (5-HT) receptor subtypes involved in secretion of water and electrolytes (sodium, potassium, and chloride) induced by luminally administered serotonin in rat jejunum and ileum in vivo. Ketanserin partially inhibited and ICS 205-930 totally inhibited serotonin-evoked secretion. Ketanserin induced mild basal secretion while ICS 205-930 alone reduced basal absorption. There were no differences in the effects of ketanserin or ICS 205-930 on serotonin-induced secretion by rat jejunum versus ileum. Neither N -acetyl-5-hydroxytryptophyl-5-hydroxytryptophanamide nor methysergide altered the secretary effect of serotonin in rat ileum. The substituted henzamides, cisapride, and BRL 24924, and the 5-HT 4 agonist, 5-methoxytryptamine, induced water and electrolyte secretion. While BRL 24924 did not alter the subsequent serotonin-induced secretory fluxes, cisapride slightly inhibited the induced secretion. These results suggest that (1) in both segments of the intestine, 5-HT 2, 5-HT 3, and/or 5-HT 4 receptor subtypes are involved in the regulation of intestinal transport of water and electrolytes under basal conditions; (2) serotonin-induced water and electrolyte secretion is mediated by pathways involving 5-HT 2, 5-HT 3, and 5-HT 4 receptor subtypes in both rat jejunum and ileum; (3) 5-HT 1 receptors do not seem to be involved in the mediation of intestinal water and electrolyte transport; (4) these effects are similar to those described for systemically administered 5-HT.

Endotoxin-induced alterations in rat colonic water and electrolyte transport

This study examines the effects of endotoxin on intestinal water and electrolyte transport in adult male rats. Endotoxin (1.55 mg/kg, intravenously) reduced in vivo colonic saline absorption 61% in 1 hour. In vitro unidirectional and net 22Na and 36Cl fluxes showed that endotoxin significantly decreased net colonic 22Na absorption compared with control colons (0.3 ± 1.7 vs. 4.8 ± 1.1 μEq/h × cm2). Although endotoxin had no significant effect on basal short circuit current (Isc) and conductance, 3H-inulin flux studies suggested an increase in colonic permeability. Isc responses to the 5′-cyclic adenosine monophosphate (cAMP)-dependent secretagogues prostaglandin E2 (1 μmol/L) and vasoactive intestinal peptide (0.1 μmol/L) were diminished by 80% and 50%, respectively. However, cytosolic cAMP-dependent protein kinase activity under basal and stimulated (6 μmol/L 8-bromo-cAMP) conditions was not altered by endotoxin treatment. The Isc responses to 10 μmol/L bethanechol, a Ca2+-dependent agonist, were not effected by endotoxin treatment. It was concluded that endotoxin significantly affects colonic transport function and may contribute to the development of diarrhea in inflammatory bowel diseases.

Pharmacoeconomics of the therapy of diarrhoeal disease.

We review the pathophysiology of intestinal water and electrolyte transport leading to diarrhoea, the currently available pharmacological strategies for its treatment, and the economic implications of such treatments. Diarrhoea occurs most frequently and is associated with highest mortality in children under 5. Oral rehydration therapy (ORT) is the cornerstone of its management. The safety and efficacy of ORT in the prevention of death from dehydration, both in field and also in hospital settings, are now well established. Because it is also inexpensive, ORT is widely applicable worldwide. More recently, rice-based ORT has emerged, based on well known traditional remedies for diarrhoea in southeast Asia and the Far East. Rice-based ORT has the advantage of being more culturally acceptable, readily available even in rural homes in developing countries, and is more effective in reducing stool output and the duration of diarrhoea, compared with conventional glucose-electrolyte solutions such as World Health Organization ORT. For infants, the well known antidiarrhoeal properties of human milk needs emphasis for a variety of reasons including economic ones. Data concerning the economic benefits to a nations' health budget as a result of nationwide implementation of oral rehydration solution (ORS) use are limited. Available data from individual centres in developing countries, if projected to national level, would incur considerable economic advantage. Except for a few notable infections such as shigellosis, cholera, amoebiasis and giardiasis, the widespread use of antibiotics in acute diarrhoea, still a common practice in many developing countries, has no proven value and may be detrimental. The economic implications of antibiotic abuse in the treatment of diarrhoea in developing countries is enormous. Despite the availability of a wide spectrum of pharmacological agents for diarrhoea reviewed in this article, only a few such agents are of proven clinical efficacy: corticosteroids, aminosalicylates and immunosuppressants in the treatment of inflammatory bowel disease and opioid derivatives such as loperamide which may be useful in protracted diarrhoea in children and in disorders where rapid gastrointestinal transit is the main cause of diarrhoea. Opioids are not recommended for acute infective diarrhoea in childhood. Octreotide, a somatostatin analogue, is reported to be useful in the treatment of secretory diarrhoea due to noninfective causes and in the treatment of intractable diarrhoea associated with AIDS. Its high cost and need for parenteral administration prevent its wider application.(ABSTRACT TRUNCATED AT 400 WORDS)

Characterization of small intestinal water, sodium, and potassium transport and morphology in the pig.

The suitability of the young pig for studies of intestinal transport was investigated by determination of net water, sodium, and potassium absorption, and morphometry in jejunum and ileum. Active net absorption was seen in both jejunum and ileum. There was no difference in absorption between segments and there was a good correlation between water and electrolyte transport. Heart rate, arterial pressure, and absorption were constant with time. Villus height and width were similar to those of human, but crypt depth was greater, and the ratio of villus height to crypt depth less. The mucosa was partially permeable to polyethylene glycol 4000 and this marker is not suitable for studies of transport in young pigs.

Effect of base precursors on water and electrolyte transport during oral hydration solution perfusion in secreting rat intestine

In situ steady-state, single-pass small intestine perfusions in rats were carried out to compare the effect of the bicarbonate and citrate World Health Organization oral rehydration solutions and a base precursor-free solution on intestinal water and electrolyte transport after inducing intestinal secretion with purified heat-stable Escherichia coli enterotoxin. When toxin was not perfused, the rates of water, sodium, and bicarbonate absorption were significantly greater from the bicarbonate-containing solution than from the citrate or base precursor-free solutions. Chloride absorption was greater from the base precursor-free solution, but this might reflect the higher chloride concentration of the perfusate. When toxin was perfused, there was no significant difference among the solutions in the rates of water, potassium, or chloride absorption. Sodium absorption occurred at significantly greater rates from both the bicarbonate and the base precursor-free solutions than from the citrate solution. Base precursor-containing solutions may not provide any advantage over a base precursor-free solution in stimulating water and sodium absorption in 5'-cyclic guanosine monophosphate mediated acute diarrhea.

Short-chain glucose polymer and anthracene-9-carboxylic acid inhibit water and electrolyte secretion induced by dibutyryl cyclic AMP in the small intestine

Glucose-stimulated sodium absorption is the rationale for treatment with glucose-based oral rehydration solution in diarrhea. Concurrent treatment with pharmacological inhibitors, which specifically block chloride secretion, may be a useful adjunct to oral fluid therapy. To examine this hypothesis, the authors determined the intestinal water and ion transport rates in rat small intestine during the secretory phase induced by perfusion with N6-2′-0-dibutyryl adenosine 3′,5′-cyclic monophosphate (dbcAMP), 1.0 mmol/L. A marker (polyethylene glycol 4000) dilution technique was used to evaluate the antisecretory effects of a defined short-chain glucose polymer, d-glucose, and a chloride channel blocker, anthracene-9-carboxylic acid (A-9-C). The results showed that dbcAMP induced small intestinal water and chloride ion secretion rapidly and reliably. The 2.5% concentration of rice short glucose polymer (G2, 22.7%; G3, 28.2%; G4, 14.0%; G5, 16.6%; G6, 11.6%; G7–9, 6.9%) is a better carbohydrate than the 2.5% concentration of d-glucose in reversing secretion of water, chloride, and sodium ions induced by dbcAMP. The combination of A-9-C and the glucose polymer can reverse dbcAMP-induced intestinal secretion and produces significantly (P < 0.05) better antisecretory effect on water, sodium, and chloride ions than d-glucose with A-9-C.

Only pharmacological doses of atrial natriuretic peptide affect intestinal ion transport in non-volume expanded rats.

Pharmacological doses of atrial natriuretic peptide were infused into rats to study its effect on intestinal transport. Saline control or two concentrations of rat alpha atrial natriuretic peptide (0.06 or 1.0 nmol/min/kg) were administered intravenously (1 ml) over one hour. Jejunal net transport of water and electrolytes was measured with a plasma-like luminal electrolyte solution using a 'closed loop' technique. Distal colonic potential difference and arterial blood pressure were monitored continuously. Blood samples for analysis of plasma atrial natriuretic peptide concentrations were taken at the end of the experiments. Plasma concentrations were increased (mean (SD) (2.1 (0.5) and 24.0 (1.1) nmol/l respectively) compared with the controls (0.023 (0.016) nmol/l). Blood pressure dropped by 30% (p less than 0.05) in both groups of rats receiving atrial natriuretic peptide but remained unchanged when control saline was infused. Jejunal net absorption was reduced (p less than 0.01) only in animals receiving the higher concentration of peptide (H2O from 173 (33) to 64 (69) microliters.h-1.cm-2, Na from 25.7 (5.3) to 10.9 (8.9) mumol.h-1.cm-2). Distal colonic potential difference was not affected by atrial natriuretic peptide. In conclusion massive doses of atrial natriuretic peptide are required to produce any change in intestinal salt and water transport in normal, non-volume expanded rats; these effects could be a non-specific or 'toxic' response.

Effect of neuropeptide Y on jejunal water and ion transport in humans

Neuropeptide Y is a neurotransmitter in enteric and postganglionic sympathetic neurons. In animal models of intestinal water and ion transport, neuropeptide Y decreases stimulated secretion but has no consistent effect on basal transport. In the present study, the effect of neuropeptide Y on jejunal water and electrolyte transport in healthy volunteers was investigated under basal conditions and during intestinal secretion induced by intraluminal administration of prostaglandin E2. The triple-lumen tube technique was used for perfusion of the small intestine with a plasmalike electrolyte solution containing polyethylene glycol as a nonabsorbable volume marker. After an initial control period (saline IV) neuropeptide Y was administered IV at a dose of 400 pmol · kg−1 · h−1. Neuropeptide Y significantly increased net absorption of water, sodium, potassium, and chloride under basal conditions. The peptide significantly reduced the secretion of these electrolytes induced by an intraluminal prostaglandin E2 concentration of 5 μmol/L and reduced net water secretion by 36%. The results of the current study suggest that neuropeptide Y can change intestinal water and ion transport from secretion toward absorption.

Immune System Control of Intestinal Ion Transport

SummaryThe immune system takes part in the regulation of intestinal water and electrolyte transport through the release of inflammatory mediators that act both directly and via the enteric nervous system to inhibit NaCl absorption and stimulate electrogenic Cl– secretion. It is likely that immune system activation is a normal physiologic event. The intestinal tract is filled with antigens and, although the barrier function of the epithelium usually serves to prevent their transmigration into the lamina propria, it probable that, on occasion, antigen presentation does occur. Under these instances, the phagocytes may instantly respond by initiating an intestinal secretory response that washes these antigens away. Similarly, previous sensitization to dietary antigens may allow mast cell degranulation to initiate a cleansing secretory response. Certainly under pathological conditions such as infection with parasites, bacteria, and viruses, the immune-mediated intestinal secretory response can either wash away...

Intestinal water transport in juvenile atlantic salmon ( Salmo salar L.) during smolting and following transfer to seawater

1. 1. The rate of mucosal to serosal water movement was measured in vitro in non-everted midgut segments in Atlantic salmon ( Salmo salar L.) during parr-smolt transformation (February–July) and following transfer of smolts to seawater in May. 2. 2. The rate increased significantly during smolting from 5.61 μl/cm 2/hr in the parr (February) to 11.03 μl/cm 2/hr in smolts in May. 3. 3. Measured at intervals over a period of 20 days in seawater, the rate of water transport was not significantly different from that found in the freshwater-adapted smolts (11.20 μl/cm 2/hr). 4. 4. Intestinal water transport is sodium-linked and inhibited by ouabain but is not stimulated by cortisol.

Treatment of endocrine and nonendocrine secretory diarrheal states with Sandostatin ®

Endocrine tumors of the gastroenteropancreatic (GEP) axis elaborate excessive amounts of peptides that are potent intestinal secretagogues. The actions of these peptides on intestinal transport of water and electrolytes lead to the accumulation of fluid in the intestinal lumen and diarrhea. One of the most clinically relevant secretagogues is vasoactive intestinal polypeptide (VIP). Other relevant secretagogues elaborated from tumors are serotonin, prostaglandins, and kinins. Sandostatin ® (octreotide, Sandoz, Basle, Switzerland), a long-acting octapeptide analog of somatostatin, inhibits experimentally induced intestinal secretion and has been used successfully to treat patients with secretory diarrhea refractory to other pharmacotherapy. The effective dose is in the range of 50 to 200 μg, given subcutaneously two or three times daily. The mechanism for the inhibitory effect on secretion is not clearly understood but it appears to involve inhibition of the adenylate cyclase-cyclic adenosine monophosphate system as well as interference with calcium as an intercellular mediator of enterocyte secretion. A particularly interesting use of this drug has been to treat the watery diarrhea seen in patients with acquired immunodeficiency syndrome. It is also effective in other types of secretory diarrhea not associated with endocrine tumors. These include diabetic diarrhea, idiopathic secretory diarrhea of infancy, and high output ileostomy diarrhea.

Hydrogen peroxide stimulates rat colonic prostaglandin production and alters electrolyte transport.

The changes in short circuit current (electrogenic Cl- secretion) of rat colon brought about by xanthine/xanthine oxidase in the Ussing chamber were inhibited by catalase and diethyldithiocarbamate, but not by superoxide dismutase. These results, the reproduction of the response with glucose/glucose oxidase and with exogenous H2O2, and the lack of effect of preincubation with deferoxamine or thiourea implicate H2O2, and not O2- or OH., as the important reactive oxygen metabolite altering intestinal electrolyte transport. 1 mM H2O2 stimulated colonic PGE2 and PGI2 production 8- and 15-fold, respectively, inhibited neutral NaCl absorption, and stimulated biphasic electrogenic Cl secretion with little effect on enterocyte lactic dehydrogenase release, epithelial conductance, or histology. Cl- secretion was reduced by cyclooxygenase inhibition. Also, the Cl- secretion, but not the increase in prostaglandin production, was reduced by enteric nervous system blockade with tetrodotoxin, hexamethonium, or atropine. Thus, H2O2 appears to alter electrolyte transport by releasing prostaglandins that activate the enteric nervous system. The change in short circuit current in response to Iloprost, but not PGE2, was blocked by tetrodotoxin. Therefore, PGI2 may be the mediator of the H2O2 response. H2O2 produced in nontoxic concentrations in the inflamed gut could have significant physiologic effects on intestinal water and electrolyte transport.

ANP INDUCES WATER AND ELECTROLYTE SECRETION IN THE IN VIVO RAT PERFUSED JEJUNUM

Atrial natriuretic peptide (ANP) is involved in the renal regulation of water and electrolyte homeostasis. ANP exerts its effects through the stimulation of the guanylate cyclase (GC)-cGMP system. Conflicting data have been reported concerning the effects and the mechanism of action of ANP in the intestine. Aims of the work were: 1) to see whether ANP affects the intestinal water and electrolyte transport and 2) to investigate its mechanism of action and namely the binding of ANP to intestinal cells or membranes and its effects on the GC-cGMP system. Intravenous administration of ANP (0.3ug/Kg/30min) resulted in a significant shift of water, sodium and chloride absorption toward secretion in the vivo perfused rat jejunum. Such effect was prompt, but of short duration (less than 10 minutes on a continued ANP infusion). No effect was observed on potassium transport. The effects of the addition of 3-28 rat ANP in a concentration range of 10−8 to 10−SM on GC and on cGMP were studied using rat jejunal homogenates and rat jejunal cells. GC and cGMP were measured at various times after the addition of ANP. 2 minutes after the addition on ANP, a modest (1.5 times) increase of both GC and cGMP was observed which rapidly returned to basal levels. No specific binding was obtained by incubating 125I-ANP with basolateral membranes, cells or homogenates prepared from rat jejunum. We conclude that ANP may play a role as a short-lived modulator in the intestinal regulation of water and electrolyte homeostasis. The mechanism of such interaction appears to be indirect, since it does not involve the GC-cGMP system nor is mediated by specific binding sites on the enterocyte.