Ileal Water Research Articles

In Vivo Sugar Diffusion in the Ileal Epithelium of Spontaneously Hypertensive Rats

Background: D -glucose absorption, distinguishing between active and diffusive components, was studied in the ileum of spontaneously hypertensive rats (SHR) and their normotensive control Wistar-Kyoto (WKY) rats. Net water transport was also determined. Methods: A perfusion system in vivo with ileum loops was used, and experiments with phlorizin, phloretin and 2,4,6-triaminopyrimidine (TAP) were performed in order to discriminate between active and diffusive components and between transcellular and paracellular routes. Results: A significant decrease in total D -glucose absorption was found in SHR compared to WKY rats, this reduction being due to a lower SGLT1-mediated component. The effect was not compensated by the total diffusive component, since the phlorizin-insensitive D -glucose absorption did not significantly change between rat strains. However, the diffusive component of D -glucose transport was relatively more important in hypertensive than in normotensive rats. The use of 2,4,6-triaminopyrimidine (TAP), which blocks the transport across the paracellular route, showed that the paracellular diffusion of D -glucose was higher in SHR than in WKY rats. Intestinal net water absorption was not modified between either group of animals, though the presence of phlorizin in the perfusate decreased the ileal water absorption to a greater extent in normotensive rats. Conclusion: The observed reduction in D -glucose absorption in vivo in the ileum of SHR was due to a decrease in the SGLT1-active component. Despite the paracellular diffusion of D -glucose being higher in hypertensive than in normotensive rats, the total diffusion component was not high enough to compensate this alteration.

Time- and surgery-dependent effects of lipopolysaccharide on gut, cardiovascular and nitric oxide functions.

Lipopolysaccharide (LPS) is considered a major effector of hypotension in septic shock, partly through increasing nitric oxide (NO) formation. LPS-activation of leukocytes that express cytokines which induce NO synthase (iNOS) has also been considered an important contributor to shock. However, LPS, cytokines, and NO are not necessarily associated with hypotensive shock. We investigated whether the timing of LPS injection after initial surgery could influence responses to LPS. E. coli LPS (17 mg/kg 0111:B4 and 026:B6 serotypes) was injected 15 or 120 min after tracheal and femoral cannulation in the anesthetized rat. LPS caused hypotension for 2 h when injected 15 min (early injection) after initial surgery. LPS decreased blood pressure for only 15 min when injected 2 h (late injection) after initial surgery. Plasma NO was increased and leukocytes were decreased after both the early and late LPS injection. Blood pressure responded the same when a second surgery (ileal cannulation and luminal perfusion) followed the early or preceded the late LPS injection. Ileal NO secretion increased and effective mucosal blood flow decreased when LPS followed gut surgery, but these did not change when gut surgery followed LPS. Plasma NO was increased and leukocytes were decreased when LPS followed gut surgery, but these did not change when gut surgery followed LPS. Ileal water absorption was not affected by LPS. These observations suggest that a desensitization to the hypotensive effect of LPS develops with time after an initial trauma. An additional gut trauma does not change the blood pressure response, but does have effects on leukocyte sequestration and NO synthesis. NO synthesis alone could not explain the effects on blood pressure.

The Na+/H+ exchange isoform NHE3 regulates basal canine ileal Na+ absorption in vivo

BACKGROUND & AIMS: Three different Na+/H+ exchange isoforms have been localized in mammalian ileum: Na+/H+ exchange isoform 1 (NHE1) on the basolateral membrane and NHE2 and NHE3 on the brush border membrane. The aim of this study was to determine whether NHE3 is the predominant isoform serving basal ileal Na+ absorption. METHODS: Immunocytochemistry was performed on canine ileum with specific polyclonal antibodies. Absorption studies (n = 58) were performed in dogs with 25-cm ileal Thiry-Vella fistulas. In groups 1-4, luminal 5- (N,N-dimethyl)-amiloride (DMA) was administered at doses of 100 nmol/L, 5 mumol/L, and 0.7 mmol/L to inhibit NHE1, NHE2, and NHE3, respectively. In groups 5-8, 1 mmol/L phlorizin (PHLZ), 0.7 mmol/L DMA, and 1 mmol/L PHLZ plus 0.7 mmol/L DMA were administered intraluminally. RESULTS: NHE2 and NHE3 were present in the brush border of canine ileal villus epithelial cells. The highest concentration of DMA (0.7 mmol/L) caused a significant reduction (P > 0.05) in basal ileal water and sodium absorption. PHLZ and 0.7 mmol/L DMA each alone significantly reduced basal ileal absorption (P > 0.05), whereas PHLZ plus 0.7 mmol/L DMA had an additive effect. CONCLUSIONS: NHE3 seems to be the Na+/H+ exchange isoform involved in the modulation of basal ileal water and sodium absorption. Both Na+/H+ exchange mediated through NHE3 and Na(+)- glucose cotransport contribute to basal ileal water and sodium absorption. (Gastroenterology 1997 Jan;112(1):174-83)

Role of brush border Na+/H+ exchange in canine ileal absorption.

Na+/H+ exchanger isoforms have been identified in mammalian intestinal enterocytes and cloned: NHE1 on the basolateral membrane regulating intracellular pH; and NHE2 and NHE3 on the brush border serving transcellular absorption in Na+. NHE1 and NHE2 are much more sensitive to inhibition by amiloride than NHE3, their in vitro IC50s for amiloride being 1 microM, 1 microM and 39 microM, respectively. This study tested the hypothesis that the brush border NHE3 isoform plays the predominant role in basal and meal-stimulated ileal absorption. Absorption studies (N = 72) were performed in dogs with 25-cm ileal Thiry-Vella fistulae. Six groups were studied over 4 hr. Perfusion with [14C]PEG and 140 mM Na+ was used to calculate absorption of water, ions, and glucose. Luminal amiloride was administered from the second to the fourth hours at doses of 20 microM in groups 3 and 4 to inhibit NHE1 and NHE2, and 1mM in groups 5 and 6 to also inhibit NHE3. A 480-kcal canine meal was ingested after the second hour in groups, 2, 4, and 6. Meal ingestion was followed by significant increases in water and electrolyte absorption. Amiloride (1 mM) caused significant reductions in basal and meal-stimulated ileal absorption, while the 20 microM dose had no effect on either. These data are consistent with the hypothesis that NHE3, but not NHE2, is involved in basal and meal-stimulated ileal water and Na+ absorption.

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.

Endogenous Nitric Oxide Promotes Ileal Absorption

Background/aims. Nitric oxide (NO) is generated in vascular endothelium and enteric neural plexuses from L-arginine by the action of nitric oxide synthase (NOS). This study tested the hypothesis that NO is a modulator of ileal water and ion transport. Methods. NADPH diaphorase staining was performed on fixed frozen sections of canine ileum. Absorption studies ( n = 80) were performed in five dogs with 25-cm ileal Thiry-Vella fistulas (TVF). Perfusion with [ 14C]PEG was used to calculate absorption of water, ions, and glucose from the TVF. Experiments comprised three 1-hr periods: basal, drug infusion, and recovery. Drugs infused luminally at 5 × 10 -4 mol/liter included l-ARG (NOS substrate), l -NAME (NOS inhibitor), l-ARG/ l-NAME combination, d -ARG (inactive enantiomer of l-ARG), l-LYS (basic amino acid control for l-ARG), and SNAP (NO donor). Results. NADPH diaphorase staining indicated NOS activity in the ileal mucosa and submucosa. l -ARG and SNAP caused significant increases in water and ion absorption, whereas l-NAME caused significant decreases. The prosecretory effect of l -NAME was completely reversed by synchronous l-ARG. d-ARG and l-LYS had no significant effects. No infused agent influenced [ 14C]PEG recovery. Conclusions. Inhibition of endogenous NO synthesis by l-NAME causes a prosecretory response for water and ions, which can be reversed by the administration of NOS substrate lARG. These results are consistent with the hypothesis that endogenous NO maintains a proabsorptive influence on water and ion transport in the ileum.

Effect of olsalazine on sodium-dependent bile acid transport in rat ileum

Olsalazine (OLZ), a relatively new form of 5-aminosalicylic acid (5-ASA), is being used for the treatment of colitis. A major side effect of olsalazine is diarrhea, reported in 12-25% of patients. One suggested mechanism for this side effect is enhanced ileal water and electrolyte secretion. We propose that OLZ may also inhibit ileal bile acid (BA) transport, resulting in choleretic diarrhea. This would result in excess BAs reaching the colon, with consequent BA-induced secretory diarrhea. Therefore, we studied the effect of OLZ on rat ileal absorption of taurocholate. BA uptake was determined in rat ileal segments, everted sacs, brush border membrane vesicles (BBMV), and Xenopus laevis oocytes. Segments and everted sacs were treated with 5 mM OLZ for 30 min prior to and throughout 10-min taurocholate (Tc) uptake. Terminal ileal BBMV were used to study the effect of OLZ on sodium-dependent bile acid uptake independent of cellular metabolism. Direct effects on the bile acid carrier were examined using Xenopus laevis oocytes expressing the cloned apical rat ileal BA transporter. In ileal segments 5 mM OLZ inhibited 10-min Tc uptake by 69.4 +/- 8.8% (P < 0.01) (N = 10 animals). Increasing concentrations of OLZ resulted in a dose-dependent inhibition of Tc uptake. Ten-minute Tc uptake with 0.5, 1.0, 2.0, 2.5, and 5 mM OLZ was inhibited by 13.5, 39.6, 49.7, and 70.5%, respectively. In BBMV, OLZ inhibited 45-sec Tc uptake in a dose-dependent manner but did not effect Na-dependent L-alanine uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Neural Mechanisms in Basal and Meal-Stimulated Ileal Absorption

The ingestion of a meal stimulates absorption from the jejunal lumen and is dependent on intact neural pathways. Few studies of ileal absorptive responses to a meal have been performed. This study tested two hypotheses: (1) a meal stimulates ileal glucose, water, and ion absorption, and (2) intact intestinal neurotransmission is necessary to maintain the basal and meal-stimulated absorptive states in the ileum. Absorption studies (n = 50) using 14 C-labeled PEG were performed on six dogs with 25-cm ileal Thiry-Vella fistulas (TVF). Four groups were randomly studied over 4 hr. Intraluminal oxethazaine (2 mg/dl) was administered to the TVF in Groups 2 and 4 after the 1st hour to produce neural blockade. A control volume of water was administered to the TVF in Groups 1 and 3 after the 1st hour. A 480 kcal meal was ingested at the end of the 2nd hour in groups 3 and 4. Ileal water, ion, and glucose absorption were increased significantly (P < 0.05) by the ingestion of a meal. TVF oxethazaine significantly reduced (P < 0.05) basal water and ion absorption but had no effect on meal-stimulated absorption. Ileal absorption of water, ions, and glucose is significantly increased by the ingestion of a meal. Basal ileal absorption appears to be partly dependent upon intact neurotransmission. Postprandial ileal absorption appears to be independent of neural blockade, implicating circulating hormones, paracrine mediators, or neurotransmission within the myenteric plexus of the enteric nervous system as the primary modulators of meal-stimulated ileal absorption.

Na+/H+ exchange mediates postprandial ileal water and electrolyte transport.

Feeding stimulates fluid and electrolyte absorption in the small intestine. Previous studies have suggested that Na+/glucose cotransport is important in initiating this response in the jejunum. The purpose of this study was to determine whether Na+/H+ exchange plays a role in meal-induced absorption. Exteriorized, neurovascularly intact jejunal and ileal loops (25 cm) were constructed in dogs. Following a two-week period of postoperative recovery, the loops of awake dogs were perfused with standard buffer alone or with increasing concentrations of amiloride, a Na+/H+ exchange inhibitor. Water, sodium, and chloride fluxes were calculated following a meal using [14C]PEG as a volume marker. The meal significantly increased absorption in both the jejunum (P < 0.001) and ileum (P < 0.01) in those animals perfused with buffer alone. More significantly, amiloride suppressed the increased absorption seen following a meal in the ileum (P < 0.001) but not the jejunum. The response in the ileum was dose dependent. These findings suggest that a major mediator of postprandial sodium and water absorption in the ileum is the Na+/H+ exchanger.

Administration of calcitonin gene-related peptide (CGRP) antiserum into the central nervous system reverses hemorrhage-induced ileal water absorption in rats: [formula omitted]. Division of Gastroenterology, Department of Medicine, University of California San Diego, La Jolla, CA

Administration of calcitonin gene-related peptide (CGRP) antiserum into the central nervous system reverses hemorrhage-induced ileal water absorption in rats: [formula omitted]. Division of Gastroenterology, Department of Medicine, University of California San Diego, La Jolla, CA

Effect of α1-adrenergic blockade on canine ileal water, electrolyte, and glucose absorption

Meal ingestion stimulates an increase in small intestinal water and electrolyte absorption. Endogenous norepinephrine may at least partially mediate this meal-stimulated proabsorptive response. Luminally administered alpha 1-adrenergic agonists such as norepinephrine and phenylephrine cause significant small bowel absorption, which can be prevented by the selective alpha 1-adrenergic antagonist terazosin. This study tested two hypotheses: (1) a meal stimulates ileal water, electrolyte, and glucose absorption; and (2) meal-stimulated ileal absorption is mediated via alpha 1-adrenergic receptor activation. Absorption studies (N = 27) were performed on dogs with 25-cm ileal Thirty-Vella fistulas (TVF). Perfusion with [14C]PEG was used to calculate absorption of water, electrolytes, and glucose from the TVF. Three groups were randomly studied over 4 hr: (1) terazosin alone, (2) meal alone, and (3) terazosin plus meal. Terazosin (10(-4) M) was administered to the TVF in groups 1 and 3 following the first hour. A 480-kcal mixed canine meal was ingested at the end of the second hour in groups 2 and 3. Ileal water, electrolyte, and glucose absorption increased significantly in response to meal ingestion (P < 0.05). Luminal terazosin did not significantly alter basal or meal-stimulated ileal absorption. In conclusion, meal ingestion stimulates ileal absorption of water, electrolytes, and glucose. Neither basal nor meal-stimulated ileal absorption is altered by alpha 1-adrenergic receptor blockade. These data suggest that nonadrenergic neural pathways or humoral factors are the likely mediators of meal-induced intestinal absorption.

Nitric Oxide Modulates Water and Electrolyte Transport in the Ileum

To test the hypothesis that nitric oxide is a modulator of ileal water and ion transport. Nitric oxide is produced in the vascular endothelium and enteric neural plexuses of the intestine and is involved in gastrointestinal motility and smooth muscle contractility. Little is known about the role of nitric oxide in intestinal epithelial transport. Ten-centimeter rabbit ileal segments (n = 50) were vascularly perfused with an electrolyte solution containing red cells. The lumen was perfused with a solution containing 14C-PEG. Net fluxes of water and ions were calculated during three 20-minute periods: basal, drug infusion, and recovery. Perfusion pressure was recorded to document changes in vascular resistance. Agents infused included the nitric oxide synthase substrate L-arginine, the nitric oxide source sodium nitroprusside, the substrate control D-arginine, and the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester. L-arginine and sodium nitroprusside caused absorption of water and ions. NG-nitro-L-arginine methyl ester caused secretion of water and ions, which was prevented by synchronous infusion of L-arginine. Infusion of D-arginine had no effect. Both L-arginine and sodium nitroprusside caused mild vasodilation. Inhibition of endogenous nitric oxide synthesis by NG-nitro-L-arginine methyl ester causes secretion of water and ions. This secretion is reversed by administration of the nitric oxide synthase substrate L-arginine. These findings are consistent with the hypothesis that endogenous nitric oxide has a proabsorptive influence over the ileum in the basal state.

Luminal adrenergic agents modulate ileal transport: Discrimination between α1 and α2 receptors

Luminal α-adrenergic agonists alter ileal water, ion, and glucose transport by a local mechanism. This study tested the hypothesis that luminal adrenergic agents modulate ileal transport selectively, via specific α 1 and α 2 receptors. Absorption studies (n = 72) were performed on dogs with 25-cm ileal Thiry-Vella fistulas (TVF). Perfusion with ( 14C) polyethylene glycol was used to calculate absorption of water, ions, and glucose from the TVF. Experiments included four 1-hour periods. Agonists used were phenylephrine ( α 1), clonidine ( α 2), and norepinephrine ( α 1 > α 2 and β). Antagonists used were terazosin ( α 1) and yohimbine ( α 2)- Phenylephrine and norepinephrine caused significant increases in water and ion absorption (p < 0.05). Clonidine caused significant decreases in water, ion, and glucose absorption (p < 0.05). Terazosin and yohimbine had no effect alone. Terazosin prevented the proabsorptive effect of phenylephrine and norepinephrine, and yohimbine blocked the prosecretory effect of clonidine. Yohimbine significantly increased the norepinephrine-induced proabsorptive effect. Luminal α-adrenergic agents selectively modulate ileal transport. Alpha 1-receptor activation causes a proabsorptive response, whereas α 2-receptor activation causes a prosecretory response. The combination of a luminally administered mixed and β-adrenergic agonist (norepinephrine) with α 2 receptor blockade (yohimbine) may prove useful in pathologic secretory states such as intestinal transplants, diabetic diarrhea, or diarrhea-associated endocrinopathies.

Site specificity and meal stimulation of the intestinal absorption of water, electrolytes, and bile acids

Ileal water and electrolyte absorption exceed jejunal absorption in both the basal and meal-stimulated states. The purposes of these experiments were to determine: (1) if luminal bile acids alter basal or meal-stimulated intestinal absorption, and (2) if there is site specificity or meal stimulation of intestinal bile acid absorption. Twenty-five centimeters of canine proximal jejunal and distal ileal Thiry-Vella fistulas were constructed. Simultaneous jejunal and ileal absorption studies (n = 88) were performed with a luminal perfusate containing polyethylene glycol labeled with radioactive carbon-14 to calculate the absorption of water, electrolytes, and the bile acid taurocholate (TC). In group 1, there was no TC in the luminal perfusate, whereas in group 2, 10 mM of TC was present in the luminal perfusate. Half of the observations were performed after a meal stimulus, which consisted of an orally ingested, 480-kcal mixed nutrient meal. Intraluminal TC did not affect basal or meal-stimulated water or electrolyte absorption. In both the basal and meal-stimulated states, ileal absorption of water, electrolytes, and TC significantly exceeded jejunal absorption (p < 0.05). A meal significantly stimulated water and electrolyte absorption in both the jejunum and ileum, but it stimulated absorption of TC in the ileum only (p < 0.05). Intraluminal TC does not alter basal or meal-stimulated intestinal water and electrolyte absorption. A meal stimulates increased water and electrolyte absorption in both the jejunum and the ileum, but it stimulates bile acid absorption in the ileum only. Bile acid absorption is site specific and responsive to a meal stimulus.

Effect of nifedipine on mouth-to-cecum transit of liquid meal in normal subjects

Nifedipine has been shown to inhibit small bowel motility and to increase ileal water and electrolyte absorption in animals, but few reports are available in human subjects. The drug has been reported to influence esophageal and colon motility in man, without affecting gastric emptying. We performed a double-blind, controlled, crossover, randomized study to investigate the effect of oral nifedipine 30 mg vs placebo on the orocecal transit time of a lactulose-labeled, liquid caloric meal in nine healthy volunteers, and its correlation with plasma nifedipine concentration. The transit time was measured using the breath hydrogen test. The drug study was preceded by a reproducibility study, which showed a mean variation in transit time of 8.3% (+/- 1%, SE). Nifedipine significantly increased orocecal transit time compared to placebo (nifedipine 131 +/- 16; placebo 104 +/- 14.5 min; P < 0.05). This effect correlated well with plasma nifedipine concentration expressed as area under the curve (r = 0.92, P < 0.004). Nifedipine 30 mg significantly delays orocecal transit of a liquid caloric meal. The small bowel is likely to be the site of action. These findings may afford a rational basis for investigating a possible antidiarrheal role of nifedipine.

Luminal Adrenergic Agonists Modulate Ileal Transport by a Local Mechanism

Intestinal transport is controlled by neural pathways, hormones, and luminal agents. Luminal adrenergic agents influence water and ion transport in the jejunum. This study tested two hypotheses: (i) luminal adrenergic agents influence ileal water, ion and glucose transport, and (ii) luminal adrenergic agents exert their effects locally and selectively. Absorption studies (n = 46) were performed on dogs with two adjacent 25-cm ileal Thiry-Vella fistulas (TVF). Perfusion with [14C]polyethylene glycol was used to calculate absorption of water, ions, and glucose from the distal TVF. Experiments were composed of three 1-hr periods: basal, luminal adrenergic agonist infusion, and recovery. In group 1 the adrenergic agonists were administered to the distal TVF: norepinephrine (α1 > α2 and β), phenylephrine (α1), clonidine (α2), and isoproterenol (β). In group 2 the adrenergic agonists were administered to the proximal TVF, with absorption measured in the distal TVF. In group 1 norepinephrine and phenylephrine caused a significant increase in water absorption (P < 0.05). Clonidine and isoproterenol caused decreased absorption of water and ions, with clonidine causing significantly decreased absorption (P < 0.05) of water, ions, and glucose. In group 2 there were no changes in distal TVF absorption. Luminal adrenergic agents did not alter the heart rate in either group. Luminal adrenergic agonists modulate ileal transport via a local mechanism. A proabsorptive response is observed with α1 agonists, while α2 and β agonists cause a prosecretory effect. Inhibition of glucose absorption appears to be selectively mediated via the α2-adrenergic receptor. Luminal proabsorptive α1-adrenergic agents may prove useful in pathologic secretory states such as intestinal transplants, diabetic diarrhea, or diarrhea-associated endocrinopathies.

Balance Studies and Polymeric Glucose Solution to Optimize Therapy After Massive Intestinal Resection

The aim of this study was to determine whether fluid homeostasis could be maintained by using a hypo-osmolar (200 to 221 mosmol/kg), relatively low-sodium (50 to 52 mmol/liter) solution that contained a glucose polymer in a 54-year-old patient with high ileostomy output attributed to short-gut syndrome and resultant prerenal azotemia. Sequential balance studies were performed to assess stool and urinary output, stool fat, and urinary electrolytes initially during intravenous rehydration and subsequently during administration of the necessary fluids and nutrients exclusively by oral supplementation. The additional effects of high-fat and low-fat diet, loperamide hydrochloride, and octreotide acetate were evaluated. When the patient sipped a hypo-osmolar oral rehydration solution while she was awake during the day and received a high dose of loperamide and a 40-g fat, disaccharide-free diet, salt and water homeostasis was maintained. The addition of octreotide did not substantially enhance fluid balance; rather, it increased fecal fat and fluid losses from the small bowel. Thus, hypo-osmolar polymeric glucose solutions maintain fluid homeostasis in patients with the short-gut syndrome. In such patients, simple balance studies are useful for assessing the absorptive capacity of the residual intestine, for developing an optimal individualized treatment, and for eliminating the need for costly, long-term home parenteral nutrition.

Effects of olsalazine and sulphasalazine on jejunal and ileal water and electrolyte absorption in normal human subjects

Effects of olsalazine and sulphasalazine on jejunal and ileal water and electrolyte absorption in normal human subjects

Effects of olsalazine and sulphasalazine on jejunal and ileal water and electrolyte absorption in normal human subjects.

The effect of sulphasalazine and olsalazine on jejunal and ileal water and electrolyte absorption was investigated in normal subjects by a steady state intestinal perfusion of a physiological glucose bicarbonate electrolyte solution in the absence and presence of increasing concentrations of each drug. (Olsalazine 0.25 g/l, 1.0 g/l, jejunum; 0.5 g/l, 1.0 g/l, ileum; sulphasalazine 0.25 g/l, 0.5 g/l, 2.0 g/l jejunum; 1.0 g/l, 2.0 g/l, ileum.) In the jejunum olsalazine at 1.0 g/l significantly inhibited water, sodium, chloride, and potassium absorption (p less than 0.05). In the ileum olsalazine at 0.5 and 1 g/l significantly inhibited glucose uptake (p less than 0.04) and water absorption (p less than 0.03). In the jejunum sulphasalazine had a dose related and significant inhibitory effect on water, bicarbonate, and sodium absorption and at 2.0 g/l an inhibitory effect on chloride, potassium (p less than 0.005), and glucose (p less than 0.05) absorption. In the ileum sulphasalazine had no significant effect on water and electrolyte absorption. All inhibitory effects were rapidly reversible. These data show that unexplained diarrhoea in patients with ulcerative colitis treated with olsalazine may occur as a consequence of inhibition of water and electrolyte absorption in the small intestine and that the mechanisms of inhibition of sulphasalazine and olsalazine are different.

Regulation of rat ileal water absorption by central ?2 adrenergic receptors

This study examined the role of central adrenergic receptors in the regulation of water absorption by the rat ileum. Clonidine, an alpha 2-adrenergic receptor agonist, increased water absorption in vivo following intracerebroventricular but not intravenous injection. Intracerebroventricular injection of prazosin, an alpha 1-adrenergic receptor antagonist, did not alter basal water absorption. Prazosin did not prevent the clonidine effect. In contrast, the alpha 2-adrenergic receptor antagonist, yohimbine, reduced basal absorption and prevented the intracerebroventricular clonidine effect. Treatment with reserpine reduced ileal norepinephrine content by 98%, reduced basal water absorption consistent with a loss of sympathetic outflow to the mucosa, but did not prevent the increase in water absorption due to intracerebroventricular clonidine. These results suggest that central alpha 2 receptors regulate water absorption by the rat ileum. The clonidine-induced increase in water absorption is not mediated by the sympathetic nerves innervating the intestine.