Jejunal Absorption Research Articles

Effect of angiotensin-(1–7) on jejunal absorption of water in rats

The effect of angiotensin-(1–7) on jejunal water absorption in rats was investigated. The jejunal sac of anesthetized rats was filled with two ml of tyrode solution containing 3.7 MBq of tritiated water. A femoral vein was cannulated for administration of peptides and drugs. Infusion of Ang-(1–7) at the dose of 0.7 ng/kg.min produced a significant increase in jejunal water absorption compared to control (32% increase). The Ang-(1–7) antagonist A-779 abolished the effect of Ang-(1–7) on water absorption. A reduction of the Ang-(1–7) effect was also produced by treatment with the AT 1 receptor antagonist, losartan or the AT 2 receptor antagonist, PD123.177. The increase in jejunal water absorption produced by Ang-(1–7) was blocked by the nitric oxide synthase inhibitor, L-NAME and by indomethacin. These data suggest that the effect of Ang-(1–7) on the jejunal loop is mediated by activation of a multiple angiotensin receptors and/or by an atypical angiotensin receptor. Furthermore, the effect of Ang-(1–7) on jejunal water absorption is mediated by nitric oxide and by a cyclooxygenase-dependent mechanism.

Route of jejunal mucosa absorption of trypsin demonstrated by immunofluorescence.

Previous studies have demonstrated the absorption of porcine trypsin in isolated jejunal loops from male Wistar rats by open-loop perfusion. The possible routes of absorption were examined in the study reported here. Trypsin (0.5 mg/ml) was dissolved in tyrode solution and perfused at a rate of 0.5 ml/min, at 37 degrees C, for 40 min. Using immunoperoxidase and immunofluorescence techniques, strong reactivity towards anti-TLCK-trypsin antibody was demonstrated through out the enterocyte cytosol. The present data indicate that trypsin was absorbed by enterocytes, probably through a transcellular route.

In ovo Peptide YY Administration Improves Body Weight at Hatch and Day 3 in Turkey Poults

Previous studies in our laboratory have demonstrated that in ovo administration of peptide YY (PYY) at Day 18 of incubation enhanced adjusted feed conversion ratio (AFCR) and BW gains of broilers during the first week post-hatch. Preliminary studies have also shown that in ovo PYY administration at Day 25 of incubation also increases jejunal glucose absorption in 1-d-old Nicholas turkey poults. The objective of this study was to further elucidate the effects of in ovo PYY administration on growth and feed conversion in two turkey lines: a commercial growth line (BUT; British United Turkey, UK) and the Egg Line. Eggs from both turkey lines were randomly placed in the same incubator. On Day 25 of incubation, 380 BUT and 440 Egg Line eggs were injected with 100 μL 1.025% saline (control) or 600 μg PYY/kg egg weight. At hatch, 168 poults from each treatment group were wing-banded, weighed, and randomly distributed across pens in four Petersime batteries. A standard turkey starter crumble feed and water were available ad libitum. Feed and birds were weighed on Days 3, 10, and 17 to determine BW gains and AFCR. Poults of both lines from PYY-treated eggs were heavier (P < 0.01) than controls at Day 3. This effect was not apparent at Days 10 and 17. A subset of birds from each treatment group was randomly chosen at Day 17 and sexed by dissection. At hatch and again at Day 3, there were noBWdifferences (P = 0.94 and P = 0.15, respectively) noted between sexes. Males were heavier at 10 and 17 d (P = 0.0001). These results suggest that PYY enhances poult weight and may attenuate differences in BW caused by gender during early post-hatch life.

Morphological and functional adaptation of the small intestine after colectomy and ileal pouch-anal anastomosis in rats

This study investigated morphological and functional changes in the small bowel after colectomy and ileal pouch-anal anastomosis (IPAA). In 15 rats electrolyte, glucose, and water absorption was determined by in vivo single-pass perfusion of the proximal and distal small intestine 15 weeks after IPAA. Afterwards the small intestine was resected for morphometric evaluation. Controls were 15 identically treated rats without operation. IPAA led to a significant increase in the small intestinal diameter and a significant increase in villus length and density, which was more apparent in ileum than in jejunum. Therefore the mucosal surface per unit serosa increased significantly by 59% in the jejunum and by 76% in the ileum. In the pouch there was a significant increase in goblet cell density, crypt depth, and diameter of the muscularis which was not detectable in the segments proximal from the pouch. Due to the increase in mucosal surface there was a significant increase in total glucose and electrolyte and sorption in the ileum while absorption rates per unit mucosa were unchanged, with the exception of an increase in mucosal sodium absorption. Jejunal absorption and ileal absorption of water remained unchanged. Adaptation of the small intestine after IPAA leads to colonic metaplasia in the pouch and intestinal hyperplasia proximal from the pouch. The loss of colonic absorption is compensated by the increase in ileal mucosal surface with subsequently elevated electrolyte and glucose absorption. Changes in intestinal permeability may be responsible for additional water depletion, which is compensated by the upregulation of enteric water and sodium absorption.

Experimental colitis decreases rat jejunal amino acid absorption: Role of capsaicin sensitive primary afferents

Ulcerative colitis and experimental colitis are known to be associated with functional and structural abnormalities of the small intestine. The aim of this study was to determine whether experimental colitis in the rat has any effect on jejunal amino acid absorption and to investigate the neural mechanisms involved. In Sprague Dawley rats, colitis was induced by intracolonic administration of 0.1 ml of 6% iodoacetamide. Alanine absorption in the jejunum was measured using the single pass intraluminal perfusion technique in vivo and the three-compartment model in vitro. Experiments were done in normal and sham treated rats, as well as in rats that underwent neonatal capsaicin treatment, adult capsaicin treatment, or subdiaphragmatic vagotomy. Colitis was more severe in rats subjected to neonatal or adult capsaicin treatment, but was not affected by subdiaphragmatic vagotomy. In rats with colitis, jejunal alanine absorption was reduced by 2% (P>0.05), 28%, 40%, and 18% (P<0.001) at 1, 1.5, 2, and 3 days post rectal iodoacetamide administration. A rebound increase of 12% above baseline was noted at 4 days (P<0.05). Similar results were noted in vitro. In rats that received two consecutive injections of iodoacetamide, the decrease in jejunal alanine absorption occurred earlier, was more severe, and persisted for more than 30 days. Neonatal as well as adult capsaicin treatment aggravated both the colitis and the decrease in jejunal alanine absorption. On the other hand, subdiaphragmatic vagotomy attenuated the decrease in jejunal alanine absorption, but had no significant effect on colitis severity. It is concluded that iodoacetamide induced colitis impairs jejunal amino acid absorption and that this effect involves vagal efferents as well as capsaicin sensitive primary afferents.

Systemic Effects of Acute Terminal Ileitis on Uninflamed Gut Aggravate Bile Acid Malabsorption

Background. Some patients with terminal ileitis suffer from significant bile acid malabsorption even if the inflammation is locally limited. We hypothesized that inflammation in the terminal ileum may lead to changes in mucosal absorption in more proximal intestinal segments and aggravate bile acid malabsorption.Methods. Five hamsters underwent laparotomy and localized instillation of 2,4,6-trinitrobenzenesulfonic acid (TNBS) in 10% ethanol into the last 4 cm of ileum to create terminal ileitis. A control group (n = 5) underwent instillation of saline. Animals were sacrificed after 24 h. Active and passive transport of radiolabeled bile acids was measured in the proximal and terminal ileum and glucose absorption in the jejunum using an everted sleeve technique. Myeloperoxidase (MPO) activity and histomorphology were examined by standard methods.Results. In animals with ileitis, active bile acid uptake decreased by 84% in the terminal ileum (t test, P <0.001) and by 58% in the proximal ileum (P < 0.05) compared with saline-treated controls. Jejunal glucose absorption decreased by 59% (P < 0.01). Passive bile acid and glucose absorption rates were not significantly changed in any segments of treated animals versus controls. Histological examination of the treated group revealed signs of acute terminal ileitis without changes in the proximal ileum and jejunum. All control tissues were uninflamed. MPO activity was 13-fold increased in the inflamed ileal samples compared with controls (P <0.001). No significant changes were seen in the proximal ileum and jejunum. There was no evidence of reflux of TNBS into proximal ileum. Nominal mucosal surface area values showed no significant changes between groups. Pretreatment of an additional group of hamsters (n = 5) with acetylsalicylic acid before TNBS instillation ameliorated the inflammatory response in the terminal ileum and largely abrogated the negative effects on ileal bile acid absorption.Conclusion. These data suggest that limited acute ileitis impairs active bile acid uptake in the terminal ileum. It also diminishes active bile acid and glucose absorption in more proximal segments of the small intestine, likely by a systemic effect. This systemic effect may aggravate bile acid malabsorption in patients with limited ileitis.

Enhancement of Jejunal Absorption of Conjugated Bile Acid by Neurotensin in Rats

Release of neurotensin (NT) from intestines is markedly stimulated by ingested fat, and NT may facilitate lipid digestion and absorption through various actions that are not fully understood. Our recent finding that NT stimulates hepatic output of bile acids only when bile delivery to the intestine is maintained has led us to investigate the effects of NT on bile acid absorption in the rat small intestine. We measured the effects of intravenous infusion of NT (3-10 pmol x kg(-1) x min(-1)) on biliary recovery of (3)H-taurocholate ((3)H-TC) and (3)H-cholate administered into proximal and distal intestines or into isolated intestinal segments in situ in biliary fistula rats. To further understand the underlying mechanisms involved, the effects of NT on intestinal absorption of (3)H-D-glucose, (3)H-leucine, (14)C-antipyrine, and (51)Cr-EDTA were investigated by monitoring the absorption of radioactivity into superior mesenteric venous blood. Infusion of NT, at doses that caused near physiologic increases in blood NT levels, increased biliary recovery of (3)H-TC from the jejunum (3.4-fold) and ileum (1.7-fold), but did not enhance absorption of (3)H-cholate. NT also facilitated transcellular uptake of (3)H-glucose and (3)H-leucine and increased paracellular uptake to (51)Cr-EDTA and (3)H-mannitol, but did not alter the absorption rate for (14)C-antipyrine. These results indicate that NT can exert a facilitative effect on intestinal bile acid absorption and return to liver. This effect of NT may involve increases in paracellular absorption and carrier-mediated transport by mechanisms not yet identified.

Concerted action of dopamine on renal and intestinal Na(+)-K(+)-ATPase in the rat remnant kidney.

The present study evaluated renal and intestinal adaptations in sodium handling in uninephrectomized (Unx) rats and the role of dopamine. Two weeks after uninephrectomy, the remnant kidney in Unx rats weighed 33 +/- 2% more than the corresponding kidney in sham-operated (Sham) animals. This was accompanied by increases in urinary levels of dopamine and major metabolites [3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid] and increases in maximal velocity values (169 vs. 115 nmol. mg protein(-1). 15 min(-1)) for renal aromatic L-amino acid decarboxylase, the enzyme responsible for the synthesis of renal dopamine. High salt (HS) intake increased (P < 0.05) the urinary excretion of dopamine and DOPAC in Unx and Sham rats. However, the urinary levels of L-3,4-dihydroxyphenylalanine, dopamine, and DOPAC in Sham rats during HS intake were lower than in Unx rats. Blockade of dopamine D(1) receptors (Sch-23390, 2 x 30 microg/kg) reduced the urinary excretion of sodium in Unx (31% decrease) more pronouncedly than in Sham (19% decrease) rats. However, inhibition of renal Na(+)-K(+)-ATPase activity by dopamine was of similar magnitude in Unx and Sham rats. In parallel, it was observed that uninephrectomy resulted in a significant reduction in jejunal sodium absorption and Na(+)-K(+)-ATPase activity in jejunal epithelial cells. In jejunal epithelial cells from Sham rats, dopamine (1 microM) failed to inhibit Na(+)-K(+)-ATPase activity, whereas in Unx rats it produced a significant reduction. It is concluded that uninephrectomy results in increased renal dopaminergic activity and dopamine-sensitive enhanced natriuresis. Furthermore, it is suggested that decreased jejunal absorption of sodium may take place in response to partial renal ablation, as an example of renal-intestinal cross talk.

Improvement of Intestinal Absorption of Macromolecules by Nitric Oxide Donor

Nitric oxide (NO) is one of the most versatile mediators in mammalian biology. In the present study, we investigated the absorption‐enhancing effects of an NO donor, 3‐(2‐hydroxy‐1‐methylethyl‐2‐nitrosohydrazino)‐N‐methyl‐1‐propanamine (NOC7), on drugs that are poorly absorbed from the gastrointestinal tract. NOC7 significantly increased the jejunal absorption of fluorescein isothiocyanate dextrans (FDs) of different average molecular weights (4000–20,000). This enhancing effect decreased as the FD molecular weight increased. Another NO donor, S‐nitroso‐N‐acetyl‐DL‐penicillamine (SNAP), also increased the absorption of FD‐4 from the jejunum. The absorption enhancement effect of NOC7 significantly decreased after coadministration with an NO scavenger, 2‐(4‐carboxyphenyl)‐4,4,5,5‐tetramethylimidazole‐1‐oxyl‐3‐oxide, sodium salt. Furthermore, the enhancement effect of NOC7 was reversed shortly after cessation of the enhancer treatment. Little damage by NOC7 to the intestinal mucosa was observed in terms of release of lactose dehydrogenase and protein from the intestinal mucosa. NOC7 also increased the absorption of FD‐4 by the colon and rectum. The findings suggest that an NO donor can improve the absorption of macromolecules from all regions of the rat intestine with very little mucosal damage and that an NO donor can act as a potent absorption enhancer. © 2000 Wiley‐Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 89:1296–1304, 2000

Effects of folic acid and amino acids supplementation on zinc intestinal absorption in the progeny of ethanol-treated rats.

This study was designed to examine the effects of supplementation with folic acid and amino acids in dams that consumed ethanol during gestation and lactation to see whether there is an improvement in the intestinal absorption of zinc in pup rats on the 21st day after birth. The rats were randomized into two groups: Ethanol-rats (EG) were administered ethanol during the pregnancy and lactation periods; the ethanol-folic acid group (EFG) received a folic acid and amino acid supplement concomitantly with ethanol administration during pregnancy and lactation. The dams were mated to obtain the first offspring. Two sets of experiments were performed on the offspring at 21 days after birth. In general, in the first set, jejunal zinc absorption in the offspring of EG and EFG groups showed a gradual increase along with increased perfusion time at all assayed concentrations. Jejunal zinc absorption expressed as nmol/intestinal surface was higher in the ethanol-folic acid group than in ethanol animals at all assayed concentrations except at 25 microM concentration. In the second set of experiments, distal ileum zinc absorption in the offspring of ethanolfolic acid dams showed a significant increase at all concentrations tested. These results indicate that supplementation of folic acid and amino acids to dams that consume ethanol during gestation and lactation increase serum and milk zinc levels, although the zinc ingestion is lower. In pups of the supplemented dams, the jejunal and ileal absorption of zinc increased; as a consequence, the serum zinc levels increased. The activity of alcohol dehydrogenase, a metaloenzyme dependent on zinc levels, also increased.

Nuclear scintigraphic assessment of intestinal dysfunction after combined treatment with 9-amino-20(S)-camptothecin (9-AC) and irradiation

Purpose: The camptothecins (CPTs) are potent radiosensitizers of malignant tumors in vivo. The extent of normal tissue damage after combined CPT and radiation treatment is unknown. In this article, a jejunal absorption assay with 99mTc- pertechnetate (Na[ 99mTcO 4]) was used to assess C3H/Kam mice given total body irradiation (TBI) of 4 Gy, 6 Gy, and 8 Gy, 2 mg/kg single intramuscular injection of 9-AC or a combination of 2 mg/kg 9-AC + 4 Gy TBI. We also correlated the absorption data with morphologic changes in the jejunal mucosa. Materials and Methods: ( 99mTcO 4) − absorption from the intestinal lumen into the circulation was studied with dynamic γ-scintigraphy combined with a multichannel analyzer to record the radiometry data in a time-dependent fashion. Jejunal cross sections were scored for the number of cells per villus and the percentage of apoptotic and mitotic cells in the crypt compartment. The jejunal microcolony assay was used to quantify jejunal crypt survival. Results: A dose-dependent decrease in the absorption function was observed 3.5 days following TBI. The mean absorption rate was reduced to 89 ± 16% of control in response to a sublethal 4 Gy TBI and dropped to 47.5 (9.8% in response to 8 Gy TBI. The mean rate of intestinal absorption was delayed by single sublethal 2 mg/kg 9-AC injection to 62 (11% in comparison with control values. The combination of a single 4 Gy TBI with a 9-AC treatment decreased the ( 99mTcO 4) − jejunal absorption in an additive fashion producing absorption lifetime values more than twofold longer than controls. The decrease in ( 99mTcO 4) − absorption at 3.5 days after irradiation, 9-AC treatment or the combination of the two agents correlates with the number of cells per villus and the percentage of apoptotic cells in the crypt compartment. Conclusion: Dynamic enteroscintigraphy with 99mTc-pertechnetate is a sensitive functional assay for rapid evaluation of radiation and chemotherapy induced intestinal damage. Reduced intestinal absorptive function has a cellular basis and correlates directly with the numbers of cells lost per villus in a treatment-dependent manner.

Calcitonin gene-related peptide regulates amino acid absorption across rat jejunum

The calcitonin gene related peptide (CGRP) is widely distributed in the enteric nervous system and gut afferents. Its role in normal digestion and absorption is not characterised. This study is conducted to elucidate whether CGRP regulates amino acid absorption in the small intestine. In in vivo experiments using the single-pass perfusion technique, intravenous infusion of CGRP (250–750 pmol/kg-min) reduced alanine absorption by 35–40%. The effects were completely blocked by the antagonist hCGRP (8–37). Moreover, intravenous infusion of CGRP antagonist blocked the inhibitory effect of intraluminal capsaicin perfusion on alanine absorption. Similarly, intracerebral injection of CGRP decreased alanine absorption, an effect which was reduced by vagotomy. In vitro experiments using isolated jejunal strips showed that CGRP reduced alanine absorption in a dose-dependent manner. At 6 pM, CGRP decreased alanine absorption by 33%. Similarly, CGRP reduced the absorption of proline and taurine by 20 and 11.5%, respectively. Kinetic studies revealed that CGRP reduces alanine influx into intestinal epithelial cells by inhibiting the affinity of the carriers. It is demonstrated that CGRP is involved in the regulation of jejunal amino acid absorption through intrinsic (enteric) and extrinsic (central) neural mechanisms.

Nuclear scintigraphic assessment of radiation-induced intestinal dysfunction.

Radiation-induced damage to the intestine can be measured by abnormalities in the absorption of various nutrients. Changes in intestinal absorption occur after irradiation because of loss of the intestinal absorptive surface and a consequent decrease in active transport. In our study, the jejunal absorption of (99m)Tc-pertechnetate, an actively transported gamma-ray emitter, was assessed in C3H/Kam mice given total-body irradiation with doses of 4, 6, 8 and 12.5 Gy and correlated with morphological changes in the intestinal epithelium. The absorption of (99m)Tc-pertechnetate from the intestinal lumen into the circulation was studied with a dynamic gamma-ray-scintigraphy assay combined with a multichannel analyzer to record the radiometry data automatically in a time-dependent regimen. The resulting radioactivity-time curves obtained for irradiated animals were compared to those for control animals. A dose-dependent decrease in absorptive function was observed 3.5 days after irradiation. The mean absorption rate was reduced to 78.8 +/- 9.3% of control levels in response to 4 Gy total-body irradiation (mean +/- SEM tracer absorption lifetime was 237 +/- 23 s compared to 187 +/- 12 s in nonirradiated controls) and to 28.3 +/- 3.7% in response to 12.5 Gy (660 +/- 76 s). The decrease in absorption of (99m)Tc-pertechnetate at 3.5 days after irradiation correlated strongly (P < 0.001) with TBI dose, with the number of cells per villus, and with the percentage of cells in the crypt compartment that were apoptotic or mitotic. A jejunal microcolony assay showed no loss of crypts and hence no measured dose-response effects after 4, 6 or 8 Gy TBI. These results show that dynamic enteroscintigraphy with sodium (99m)Tc-pertechnetate is a sensitive functional assay for rapid evaluation of radiation-induced intestinal damage in the clinically relevant dose range and has a cellular basis.

Role of Na+-glucose cotransport in jejunal meal-induced absorption.

In awake dogs, meal ingestion stimulates the absorption of water and electrolytes from neurovascularly intact jejunal Thiry-Vella loops, even though these loops are isolated from the remainder of the gut. This study was designed to investigate the role of Na+-glucose cotransport in mediating this event. Meal ingestion enhanced absorption when the jejunal lumen was perfused with an isotonic solution containing D-glucose, D-galactose, or 3-O-methylglucose. This response was absent when the perfusate contained mannitol or when phlorizin was added to the D-glucose solution. Mucosa from the jejunal loops was serially biopsied and assayed for brush-border Na+-glucose cotransporter (SGLT1) mRNA and protein expression. Although no changes in SGLT1 mRNA levels were observed, protein levels significantly increased within 30 min following meal ingestion. The time course of SGLT1 protein expression corresponded with that of increased Na+ and water absorption. These results suggest that meal-stimulated jejunal absorption may be mediated through an induction of mucosal SGLT1.

In vivo Measurements of Glucose Absorption in Preterm Infants

Few data are available regarding the kinetics of glucose absorption in the preterm infant. In order to ascertain the kinetics of glucose absorption in the premature infant and how rate of infusion and concentration affect absorption, jejunal glucose absorption kinetics were measured in 16 preterm infants by infusing 1, 10, and 100 mM glucose solutions in random order. Seventeen infants were perfused with glucose (100 μmol/min) by infusing 67 mM glucose at 1.5 ml/min and 133 mM glucose at 0.75 ml/min to determine the effect of changes in rate of infusion vs. concentration on glucose absorption. K_m and V_max were related to postnatal age. K_m was correlated inversely with the percentage of feedings received as human milk. Antenatal administration of glucocorticoids appeared to increase V_max. The higher infusion rate resulted in greater glucose absorption than the higher concentration glucose solution. Conclusions: The characteristics of glucose absorption in the preterm infant change with age and are affected by diet, glucocorticoids, and the method of infusion. These data have implications for the feeding of preterm infants.

Folic acid intestinal absorption in newborn rats at 21 day postpartum: Effects of maternal ethanol consumption

This study was designed to examine the effects of prenatal and postnatal exposure of ethanol in the in vivo absorption of free folic acid in the small intestine in pups rats at the 21 st day after birth. The rats were accustomed to increasing amounts of ethanol (5 to 20%, vol/vol) in tap water for 1 month. During pregnancy and suckling period, ethanol-fed dams were assigned again to ethanol 20% in drinking water. Two sets of experiments were performed. In the first set, jejunal free folic acid absorption in control group and litters nursed by dams receiving ethanol showed a gradual increase along with the increase of perfusion time at all the assayed concentrations. In general, in litters of ethanol-fed dams, jejunal free folic acid absorption expressed as nmol/intestinal surface, nmol/g tissue wet weight and nmol/g tissue dry weight were higher than in control animals. In the second set of experiments, in distal ileum loops, free folic acid absorption did not occur in control pups, but appeared in litters exposed to ethanol. Milk folic acid levels are significantly decreased in ethanol-treated dams. However, only a slight decrease in the serum folic acid levels occurs in litters of ethanol-fed dams. In conclusion, the results obtained in the present work suggested a different pattern of free folic acid absorption in distal ileum for the two groups. The exposure of rats to ethanol during the pregnancy and suckling period, can affect postnatal development of intestinal functions and could play a role in the genesis of malnutrition observed in the infant.

Jejunal permeability in humans in vivo and rats in situ: investigation of molecular size selectivity and solvent drag.

The mechanisms controlling rates and routes for intestinal absorption of nutrients and small compounds are still not fully clarified. In the present study we aimed to investigate the effect of solvent drag on intestinal permeability of compounds with different molecular sizes in humans and rats. The effective intestinal permeabilities (Peff) of hydrophilic compounds (MW 60-4000) were determined in the single-pass perfused jejunum in humans in vivo and rats in situ under iso- and hypotonic conditions. The transport mechanism(s) of water and the importance of the solvent drag effect were investigated by the use of D2O. This is the first report in humans establishing the relation between in vivo measured jejunal Peff and molecular size for hydrophilic compounds. In addition, in rats we also found a molecular-size selectivity for hydrophilic compounds similar to man. The jejunal Peff of water and urea (MW 60) in both species were several times higher than predicted from their physicochemical properties. In humans, the jejunal absorption of urea and creatinine (MW 113) was increased by solvent drag, while no effect was found for the other investigated compounds. In rats, Peff for urea and creatinine were unaffected. In conclusion, it is still unclear if solvent drag occurs mainly through the para- or transcellular route, although, results from this study further add to our earlier reports suggesting that the transcellular route is most important from a quantitative point of view regardless of physicochemical properties of the transported compounds.

Evidence for an anion exchange mechanism for uptake of conjugated bile acid from the rat jejunum

Absorption of conjugated bile acids from the small intestine is very efficient. The mechanisms of jejunal absorption are not very well understood. The aim of this study was to clarify the mechanism of absorption of conjugated bile acid at the apical membrane of jejunal epithelial cells. Brush-border membrane vesicles from intestinal epithelial cells of the rat were prepared. Absorption of two taurine-conjugated bile acids that are representative of endogenous bile acids in many variate vertebrate species were studied. In ileal, but not jejunal brush-border membrane vesicles, transport of conjugated bile acids was cis-stimulated by sodium. Transport of conjugated bile acids was trans-stimulated by bicarbonate in the jejunum. Absorption of conjugated dihydroxy-bile acids was almost twice as fast as of trihydroxy-bile acids. Coincubation with other conjugated bile acids, bromosulfophthalein, and DIDS, as well as by incubation in the cold inhibited the transport rate effectively. Absorption of conjugated bile acids in the jejunum from the rat is driven by anion exchange and is most likely an antiport transport.

Cisplatin impairs fluid and electrolyte absorption in rat small intestine: a role for 5-hydroxytryptamine

BackgroundThe antineoplastic drug cisplatin has been widely used for the treatment of cancer in humans but its use has been limited by vomiting and diarrhoea. Cisplatin releases 5-hydroxytryptamine into the...

Compartmentalization of extracellular cGMP determines absorptive or secretory responses in the rat jejunum.

We examined potential mechanisms by which angiotensin subtype-2 (AT2) receptor stimulation induces net fluid absorption and serosal guanosine cyclic 3',5'-monophosphate (cGMP) formation in the rat jejunum. L-arginine (L-ARG) given intravenously or interstitially enhanced net fluid absorption and cGMP formation, which were completely blocked by the nitric oxide (NO) synthase inhibitor, N-nitro-L-arginine methylester (L-NAME), but not by the specific AT2 receptor antagonist, PD-123319 (PD). Dietary sodium restriction also increased jejunal interstitial fluid cGMP and fluid absorption. Both could be blocked by PD or L-NAME, suggesting that the effects of sodium restriction occur via ANG II at the AT2 receptor. L-ARG-stimulated fluid absorption was blocked by the soluble guanylyl cyclase inhibitor 1-H-[1,2,4]oxadiazolo[4, 2-alpha]quinoxalin-1-one (ODQ). Cyclic GMP-specific phosphodiesterase in the interstitial space decreased extracellular cGMP content and prevented the absorptive effects of L-ARG. Angiotensin II (ANG II) caused an increase in net Na+ and Cl- ion absorption and 22Na+ unidirectional efflux (absorption) from the jejunal loop. In contrast, intraluminal heat-stable enterotoxin of Escherichia coli (STa) increased loop cGMP and fluid secretion that were not blocked by either L-NAME or ODQ. These findings suggest that ANG II acts at the serosal side via AT2 receptors to stimulate cGMP production via soluble guanylyl cyclase activation and absorption through the generation of NO, but that mucosal STa activation of particulate guanylyl cyclase causes secretion independently of NO, thus demonstrating the opposite effects of cGMP in the mucosal and serosal compartments of the jejunum.