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G I Sandle

Publications and source records attributed to G I Sandle.

At least 37 records · Page 2Linked to original sources
PubMed1994

Potassium channels in colonic crypts.

A characteristic feature of intestinal epithelia is their ability to secrete chloride (Cl-), a process that occurs mainly in intestinal crypts and is the critical transport event in secretory diarrhoea. Increased potassium (K+) channel activity in the basolateral membrane has an important role in the Cl- secretory process by hyperpolarising the cell and maintaining a favourable electrochemical driving force for Cl- exit at the apical membrane. We have shown, using patch-clamp techniques, that the basolateral membrane of human colonic crypt cells contains low conductance K+ channels that are voltage and calcium (Ca2+) sensitive and blocked by barium (Ba2+). These K+ channels are regulated by cytosolic cyclic adenosine monophosphate (cAMP) and Ca2+, intracellular second messengers that also stimulate Cl- secretion. This population of human intestinal K+ channels may be a target for the pharmacological control of Cl- secretory diarrhoea.

Bucladesine↗
PubMed1994

Characterisation of oxidative injury to an intestinal cell line (HT-29) by hydrogen peroxide.

Reactive oxygen metabolites have been implicated in causing epithelial cell injury in colonic inflammation. A model of oxidant injury in intestinal epithelial cells has been developed in which HT-29-18-C1 cells are injured with graded concentrations of hydrogen peroxide and characterised by the MTT test. The MTT test was validated as a cytotoxicity assay and has a similar sensitivity to hydrogen peroxide induced injury as the assay of intracellular adenosine triphosphate. Exposure to a range of hydrogen peroxide concentrations (0.05-20 mM) for varying duration (5-120 min) showed that injury was dependent on time and concentration. The median lethal dose (LD50) for one hour exposure to hydrogen peroxide was approximately 0.1 mM. Injury from hydrogen peroxide was only partially reversible as determined by the MTT test and assay of cellular proliferation by crystal violet staining. There was an exponential loss of hydrogen peroxide when incubated with HT-29-18-C1 cells (t1/2 35 min). Experiments with 0.5 mg/ml aminotriazole and 0.5-2 mM buthionine sulphoximine suggested hydrogen peroxide breakdown was predominantly caused by catalase rather than glutathione peroxidase. Injury resulting from 1 mM hydrogen peroxide could be reduced by either coincubation of cells with 1,10-phenanthroline, an Fe2+ chelator, or preincubation with deferoxamine, and Fe3+ chelator, suggesting the participation of Fe2+ and Fe3+ in hydrogen peroxide induced injury. In conclusion, hydrogen peroxide induces injury in HT-29-18-C1 cells both directly and by generation of the hydroxyl radical.

Adenosine Triphosphate↗
PubMed1994

Aldosterone-induced apical Na+ and K+ conductances are located predominantly in surface cells in rat distal colon.

Aldosterone is a major regulator of Na(+)-absorptive and K(+)-secretory processes in the distal segment of mammalian colon. In this study, the distribution of aldosterone-sensitive cell types in isolated rat distal colon was determined using site-directed intracellular microelectrodes, specific Na(+)- and K(+)-channel blockers, and aldosterone-receptor binding techniques. Electrophysiological data indicated that aldosterone induced parallel apical membrane Na+ and K+ conductances, mainly in surface cells and to a significantly lesser degree in crypt cells. Scatchard analyses of aldosterone-receptor binding in cytosolic fractions revealed the maximum number of specific binding sites in whole mucosal homogenate and in the upper one-third and lower two-thirds of isolated crypt units to be 74.9 +/- 2.0, 59.8 +/- 2.4, and 59.3 +/- 3.2 fmol/mg protein, respectively, indicating the presence of aldosterone receptors in the crypt cell population. We conclude that in rat distal colon aldosterone-induced Na+ and K+ conductances (and by inference, electrogenic Na(+)-absorptive and K(+)-secretory processes) are located predominantly in the surface cell population and to a lesser extent in crypt cells, which also contain aldosterone receptors. This spectrum of aldosterone-induced Na+ and K+ conductances may reflect varying stages of differentiation along the surface cell-crypt cell axis.

Aldosterone↗
PubMed1994

Comparison of aldosterone- and RU-28362-induced apical Na+ and K+ conductances in rat distal colon.

In mammalian distal colon, aldosterone induces electrogenic Na+ absorption and electrogenic K+ secretion, whereas the sole transport effect of specific glucocorticoid agonists is thought to be stimulation of electroneutral NaCl absorption. In this study, intracellular microelectrodes and Na(+)- and K(+)-channel blockers were used to compare the effects of aldosterone and RU-28362 (a specific glucocorticoid agonist) on apical Na+ and K+ conductances in surface cells and upper crypt cells in the most distal colonic segment from adrenalectomized rats. In control animals, surface cells and crypt cells were devoid of apical Na+ and K+ conductances. In aldosterone-treated animals (70 micrograms.100 g body wt-1.day-1 for 7 days), Na+ conductances were induced in 88% of surface cells but only 40% of crypt cells, and the distribution of K+ conductances was similar (82% of surface cells and 50% of crypt cells). The same dose of RU-28362 also induced Na+ conductances in 82% of surface cells and 50% of crypt cells, which tended to be smaller than those induced by aldosterone. RU-28362, in contrast to aldosterone, had no effect on apical K+ conductance in surface cells or crypt cells. Concurrent treatment with the mineralocorticoid antagonist RU-28318 (3.5 mg.100 g body wt-1.day-1 for 7 days) inhibited Na(+)-channel expression in aldosterone-treated animals but had no effect in RU-28362-treated animals. We conclude that in the most distal segment of rat colon, aldosterone acts via mineralocorticoid receptors to induce apical Na+ and K+ conductances, which are only fully expressed in the surface cell population.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗
PubMed1993

Properties of a potassium channel in cultured human gastric cells (HGT-1) possessing specific omeprazole binding sites.

The HGT-1 human gastric cell line is similar to acid secreting parietal cells in that it possesses H2 receptors, histamine sensitive adenyl cyclase, and Cl- channels, which are activated by histamine by a cyclic adenosine monophosphate (cAMP) dependent mechanism. To discover if HGT-1 cells have additional properties found in parietal cells, [3H]omeprazole and patch clamp recording techniques were used to evaluate specific omeprazole binding sites and K+ channels in the plasma membrane. HGT-1 cells exhibited [3H]omeprazole binding in the non-stimulated state, which increased 100% in the presence of 1 mM histamine. High conductance (about 155 pS) K+ channels were active spontaneously in 17% of cell attached or excised inside out patches in non-stimulated subconfluent HGT-1 cells. In inside out patches, channel activity increased fivefold during depolarisation, ion substitution experiments confirmed that the channels were highly selective for K+, and channel activity was almost abolished by removal of Ca2+ or addition of 5 mM Ba2+. In quiescent cell attached patches, 0.1 mM dibutyryl cAMP failed to activate K+ channels. In contrast, 6.7 microM A23187 (a Ca2+ ionophore) increased intracellular Ca2+ concentration from mean (SEM) 14 (3) nM to 248 (30) nM and activated K+ channels in 21% of patches. It is concluded that the plasma membrane of HGT-1 cells possesses (a) specific 3H-omeprazole binding sites, which may reflect the omeprazole sensitive H+,K(+)-ATPase present in gastric parietal cells; and (b) Ca(2+)-activated K+ channels, which may be located in the basolateral membrane of human gastric parietal cells and play a part in acid secretion triggered by Ca(2+)-mediated secretory agonists.

Barium↗
PubMed1991

Segmental variability of glucocorticoid induced electrolyte transport in rat colon.

Recent studies suggest that the ability of glucocorticoids to reduce diarrhoea in active colitis may reflect their direct effects on distal colonic electrogenic Na+ transport and water absorption, as well as their anti-inflammatory action. To determine whether glucocorticoids induce similar changes in proximal colon, specific Na+ and K+ channel blockers (amiloride and tetraethylammonium chloride (TEA) respectively) were used to evaluate the cation transport properties of rat proximal and distal colon in vitro after three days treatment with the glucocorticoid agonist dexamethasone (600 micrograms/100 g/day). In the proximal colon, dexamethasone increased short circuit current (Isc) 2.3 fold (p less than 0.025) and total conductance (Gt) by 87% (p less than 0.015), but had negligible effects on the maximum activity of the basolateral membrane Na(+)-K+ pump and the baseline Na+ and K+ conductive properties of the apical membrane. Additional studies with diphenylamine-2-carboxylic acid (a Cl- channel blocker) suggested that the dexamethasone induced increases in Isc and Gt in proximal colon reflected stimulation of an electrogenic Cl- secretory process. In contrast, in the distal colon dexamethasone increased Isc 10 fold (p less than 0.025), Gt by 100% (p less than 0.015), and the maximum activity of the basolateral Na(+)-K+ pump by 200% (p less than 0.05), and induced substantial Na+ and K+ conductances in the apical membrane. These results indicate that dexamethasone stimulates electrogenic Na+ transport and water absorption to a significant degree only in the distal segment of rat colon. Thus in patients with active colitis, that part of the antidiarrhoeal action of glucocorticoids that reflects stimulation of electrogenic Na+ transport (and hence water absorption) may be restricted to the descending colon and rectum.

Amiloride↗
PubMed1991

Inhibition of the Na+,K(+)-ATPase pump during induction of experimental colon cancer.

During the development of large bowel cancer alterations in colonic epithelial ion transport have been observed some of which result in altered intracellular ionic composition. In many tumors intracellular sodium and potassium become elevated and depressed, respectively. This observation suggests that mechanisms governing intracellular homeostasis for sodium and potassium are no longer tightly regulated. Changes in cell membrane permeability, sodium, potassium-ATPase K(+)-ATPase) pump activity, or both may be responsible for these alterations. It is not known when during initiation and development of cancer such changes may occur. To assess whether there are changes in the Na+, K(+)-ATPase pump early during the induction of large bowel cancer and prior to any notable histological changes, we measured the kinetics of the Na+, K(+)-pump in distal colonic mucosa of CF1 mice one week following only four weekly injections of the carcinogen 1,2-dimethyhydrazine (DMH). The kinetics of the pump were found to be best described by a model of highly cooperative binding. The VMAX of the pump in premalignant mucosa was lower for both sodium and potassium substrate activation (55-65% of control) with little change in other kinetic parameters. Depression of VMAX could not be attributed to an increased barium blockable potassium conductance of the basolateral membrane. Na+,K(+)-ATPase activity was also decreased by 50% in the distal colon of DMH treated mice, but was not affected in the less cancer susceptible proximal colon. These data demonstrate that alterations occur in the Na+,K(+)-pump in premalignant mucosa months before gross tumors develop, and these changes may partially explain the altered levels of Na+ and K+ in the cytoplasm of pre-malignant and malignant colonocytes.

1,2-Dimethylhydrazine↗
PubMed1990

A cAMP-activated chloride channel in the plasma membrane of cultured human gastric cells (HGT-1).

Hydrochloric acid (HCl) secretion by gastric parietal cells involves an apical Cl- conductance, the properties of which have not been defined. In the present study, forskolin and histamine [agonists that increase intracellular cyclic adenosine monophosphate (cAMP)], and dibutyryl cAMP, activated channels in previously quiescent cell-attached membrane patches on cultured human gastric cells (HGT-1). In the cell-attached configuration (Cl- 149 mmol/l in bath and pipette), channels exhibited outward rectification, voltage dependence, inward current (-0.7 pA) at zero holding potential and a reversal potential of +24 mV, consistent with the presence of a Cl- conductive pathway. In excised inside-out patches, channels (i) exhibited degrees of outward rectification and voltage dependence that were comparable to those seen in cell-attached patches, (ii) demonstrated a -21 mV shift of their reversal potential when bath Cl- was decreased from 149 mmol/l to 53 mmol/l (calculated Cl-:cation permeability ratio 17:1), and (iii) were highly sensitive to the Cl- channel blocker diphenylamine-2-carboxylic acid (DPC, 10(-3) mol/l). This cAMP-activated Cl- channel bears many similarities to other Cl- channels within intestinal epithelia, and may represent the apical Cl- channel operating in HCl-secreting gastric parietal cells.

Adenocarcinoma↗
PubMed1990

Uncoupling of sodium chloride transport in premalignant mouse colon.

Ion transport across premalignant large bowel mucosa in CF1 mice was evaluated by measuring sodium and chloride fluxes across voltage-clamped colonic segments obtained from control animals and animals treated for 4 wk with the procarcinogen 1,2-dimethylhydrazine, which induces tumor development principally in the distal colon. In control CF1 mouse colon, the net flux of sodium was 5.1 +/- 0.7 and 4.6 +/- 0.7 microEq.cm-2.h-1 and the net flux of chloride was 6.1 +/- 1.3 and 0.8 +/- 1.2 microEq.cm-2.h-1 in the distal and proximal colon, respectively. Removal of bicarbonate decreased the net flux of sodium 1.5 +/- 0.5 and 1.9 +/- 0.7 microEq.cm-2.h-1 in the distal and proximal colon, respectively, while the net flux of chloride was decreased to 1.7 +/- 1.8 microEq.cm-2.h-1 in the distal colon but was unaltered (0.8 +/- 0.1 microEq.cm-2.h-1) in the proximal colon. Addition of 25 mM bicarbonate stimulated the net flux of sodium and chloride absorption in the distal colon but increased net flux of sodium absorption alone in the proximal colon and stimulated net flux of chloride secretion. Removal of chloride decreased net flux of sodium to 3.4 +/- 1.4 and 1.8 +/- 0.8 microEq.cm-2.h-1 in the distal and proximal colon, respectively. Addition of 20 mM Cl stimulated net flux of sodium in the distal but not the proximal colon. These data suggest that sodium absorption is mediated by an electroneutral Cl-dependent, HCO3-dependent process (i.e., Na-H Cl-HCO3 dual exchange) in control distal colon and by an electroneutral HCO3-dependent process in control proximal colon. Following 1,2-dimethylhydrazine treatment, net flux of sodium in the distal colon was not stimulated by the addition of Cl or HCO3, and transport in the proximal colon was similar to that in control animals. However, 1,2-dimethylhydrazine treatment appears to uncouple Na-H Cl-HCO3 exchange in the distal colon early in the process of large bowel carcinogenesis.

1,2-Dimethylhydrazine↗
PubMed1990

Cellular basis for defective electrolyte transport in inflamed human colon.

Electrolyte transport pathways in distal colonic mucosa from patients with noninflammatory and inflammatory (ulcerative colitis, Crohn's colitis) disease of the large bowel were studied in vitro with electrophysiological techniques. Noninflamed tissues exhibited substantial amiloride-sensitive electrogenic sodium transport. In contrast, inflamed but structurally intact tissues exhibited only a modest degree of electrogenic sodium transport, significant increases in total tissue conductance and apical membrane conductance, and a 100% increase in the arachidonic acid content of the cell membrane fraction of mucosal homogenates. Replacement of chloride with gluconate decreased total tissue conductance to a greater extent in inflamed than in noninflamed tissues, and total tissue conductance was higher in inflamed than in noninflamed tissues in the presence of transepithelial potassium and sodium gradients, suggesting enhanced mucosal "leakiness" to anions and cations in acute colitis. Apical addition of nystatin virtually abolished amiloride-sensitive apical sodium uptake in both groups, indicating that the ionophore formed channels in the apical membrane of noninflamed and diseased mucosa. Additional studies showed that mucosal inflammation decreased maximal activity of the basolateral sodium pump by 76%. Thus, defects in the biophysical properties of colonic epithelial cell membranes are likely to be important factors in the pathogenesis of diarrhea in ulcerative and Crohn's colitis.

Adult↗
PubMed1989

Segmental heterogeneity of basal and aldosterone-induced electrogenic Na transport in human colon.

Recent in vitro studies in human colon have demonstrated marked segmental differences in electrogenic Na transport. In the present study, the Na channel blocker amiloride was used further to characterise basal and aldosterone-induced electrogenic Na transport in isolated human distal and proximal colon. Bathed in NaCl Ringer solution, distal and proximal colon exhibited similar basal electrical properties, but the amiloride-sensitive short-circuit current (Isc) was 200% greater in the distal than in the proximal segment. Bathed in choline-Cl Ringer solution, total Isc decreased by 97% in distal colon and by 88% in proximal colon, indicating that Na dependent transport process(es) account almost entirely for the Isc in both segments. Substituting Na2SO4 for NaCl Ringer solution (i) increased amiloride-sensitive Isc by 56% (p less than 0.01) in distal colon but had no effect on amiloride-sensitive Isc in proximal colon, and (ii) decreased amiloride-insensitive Isc in distal and proximal colon by 52% (p less than 0.05) and 81% (p less than 0.001) respectively. After the addition of nystatin to the apical membrane, the relationship between total Isc and mucosal Na concentration indicated that the activity of the basolateral membrane Na pump was similar in both colonic segments. In a further series of experiments, exposure of distal colon to 1 mumol/l aldosterone for 5 h increased total Isc by 52% (p less than 0.05), which reflected stimulation of its amiloride-sensitive component; in contrast, aldosterone had no effect on proximal colon.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗
PubMed1989

Studies of intestinal lymphoid tissue. XII. Epithelial lymphocyte and mucosal responses to rectal gluten challenge in celiac sprue.

The immunopathologic, structural, and functional changes within rectal mucosa of known celiac sprue subjects were quantitated during local challenge with a peptic-tryptic digest of gluten. In the celiac sprue patients challenged with 2 g of digest, major effects occurred in lamina propria, submucosa, and local microvasculature. The lamina propria swelling was biphasic, starting 1-2 h after challenge with widespread extravascular deposition of fibrinogen, indicative of increased microvascular permeability, receding by 24 h postchallenge. A rapid fall in mast cells together with granule discharge suggested their involvement in this response. The late-phase swelling (48-72 h) was preceded by a rapid influx of neutrophils and basophils, the latter showing evidence of degranulation beyond 72 h. Reestablishment of vessel lumina, a rise in mast cells, and loss of neutrophils indicated tapering of the inflammatory cellular cascade by 96 h. Lymphocytes, first seen to enter the lamina by 2 h postchallenge, increased progressively, thereby resulting in substantial infiltration between 36 and 96 h. A marked rise in epithelial lymphocytes, maximal at 6-8 h, waned by 24 h. Volumes of surface and crypt epithelium remained constant throughout. In another challenge series with 4 g of gluten digest, electrical potential difference across rectal mucosa decreased significantly 12 h postchallenge, but the associated decreases in net sodium and chloride absorptive fluxes were insignificant. It is concluded that rectal mucosa is sensitized to gluten in celiac sprue disease and thus offers a promising and convenient in vivo substrate for investigative and diagnostic purposes.

Adult↗
PubMed1989

Effects of corticosteroid hormones on the electrophysiology of rat distal colon: implications for Na+ and K+ transport.

1. Conventional microelectrodes, the Na+ channel blocker amiloride (0.1 mM), and the K+ channel blocker tetraethylammonium chloride (TEA, 30 mM) were used to examine the effects of corticosteroid hormones administered in vivo on the Na+ and K+ transport properties of isolated rat distal colon. The cell membrane changes induced by aldosterone (a specific mineralocorticoid), RU 28362 (a synthetic glucocorticoid with negligible affinity for mineralocorticoid receptors), and dexamethasone (an activator of both mineralocorticoid and glucocorticoid receptors) were compared. 2. In control animals, there was no amiloride-sensitive apical Na+ conductance, and only a relatively small TEA-sensitive apical K+ conductance. 3. Hyperaldosteronism secondary to dietary Na+ depletion for 10-14 days, dexamethasone (600 micrograms 100 g-1 day-1 for 3 days), and RU 28362 (600 micrograms 100 g-1 day-1 for 3 days) induced amiloride-sensitive electrogenic Na+ transport, with the potency of aldosterone greater than dexamethasone greater than RU 28362. 4. With each corticosteroid, increased electrogenic Na+ transport reflected enhanced apical Na+ conductance, and in the case of aldosterone and dexamethasone, 3.3-fold and 2-fold increases respectively in the maximum activity of the basolateral Na+-K+ pump. In contrast, RU 28362 suppressed the maximum activity of the basolateral Na+-K+ pump by 45%. 5. All three corticosteroids enhanced the K+ conductance of the apical membrane, with the potency of aldosterone greater than dexamethasone greater than RU 28362. 6. Co-administration of spironolactone (5 mg 100 g-1 day-1) inhibited the effects of aldosterone on Na+ and K+ transport, but in dexamethasone-treated animals spironolactone resulted in a pattern of response similar to that found in RU 28362-treated animals. 7. The results support the view that mineralocorticoid receptors mediate changes in colonic Na+ and K+ transport which differ quantitatively and qualitatively from those mediated by glucocorticoid receptors. Dexamethasone and similar 'glucocorticoids' activate both types of receptor, with an overall epithelial response which mimics that induced by aldosterone.

Aldosterone↗
PubMed1988

Electrophysiology of rat distal colon after partial nephrectomy. Implications for K transport.

Previous in vivo studies in rat and man indicate that chronic renal insufficiency leads to an increase in the capacity of the large intestine for K secretion. The present studies were performed in isolated rat distal colon with conventional and K-sensitive microelectrodes to determine the cellular basis for enhanced colonic K secretion after 70% nephrectomy. The data revealed that in animals fed a regular diet, nephrectomy had no effect on the Na or K conductance of the apical membrane, or the kinetics of the basolateral membrane Na-K pump, but intracellular K activity decreased from 70 +/- 4 mmol/l to 58 +/- 4 mmol/l (P less than 0.005). In control (non-nephrectomised) animals, feeding a diet modestly (4-fold) enriched with K resulted in small but significant increases in the Na and K conductance of the apical membrane, no change in the kinetics of the basolateral membrane Na-K pump, and a rise in intracellular K activity from 70 +/- 4 mmol/l to 94 +/- 7 mmol/l (P less than 0.005). In contrast, in animals fed the K enriched diet, nephrectomy resulted in (i) large, amiloride-sensitive increases in transepithelial voltage and total tissue conductance (consistent with an appreciable degree of secondary hyperaldosteronism), (ii) marked increases in the Na and K conductance of the apical membrane, (iii) significant hyperpolarization of the basolateral membrane, (iv) a 100% increase (P less than 0.02) in the maximum activity of the basolateral membrane Na-K pump, and (v) a rise in intracellular K activity from 94 +/- 7 mmol/l to 129 +/- 7 mmol/l (P less than 0.0025). These data suggest that the combination of modest dietary K enrichment and 70% nephrectomy stimulated an active K secretory process which reflected an increase in the K excretory load applied to the colonic mucosa, and the effects of aldosterone. In this model of renal insufficiency, enhanced K secretion by the transcellular and paracellular (potential-dependent) pathways results in a marked rise in the K excretory capacity of the colon.

Animals↗
PubMed1987

Sodium transport in a mouse model of colonic carcinogenesis.

Following 4 weeks of s.c. injections of 1,2-dimethylhydrazine, a carcinogen that produces colon cancer in CF1 mice, an increase in the unidirectional mucosal to serosal flux and net absorption of sodium was observed in the distal colon. This increase in sodium transport was amiloride sensitive. 1,2-Dimethylhydrazine treatment had no effect on sodium transport in the distal colon of DBA/2 mice, a strain which does not develop colonic malignant transformation. Although stimulation of sodium transport has been observed in cultured cell systems exposed to growth factors, similar changes in sodium transport have not previously been demonstrated in an intact epithelium at an early stage of carcinogenesis. The present study in mouse distal colon demonstrates that sodium transport is altered in 1,2-dimethylhydrazine-induced malignant transformation of the large bowel.

1,2-Dimethylhydrazine↗
PubMed1987

Segmental variability of membrane conductances in rat and human colonic epithelia. Implications for Na, K and Cl transport.

The membrane conductances in proximal and distal segments of rat and human colon were studied with microelectrodes, nystatin, ion channel blockers and Cl replacement. The results reveal that (1) in rat colon, total conductance (Gt) is greater in the proximal segment than in the distal segment, reflecting greater values of apical (Ga) and paracellular shunt (Gs) conductances in the proximal segment; in contrast, in human colon, Gt and its individual membrane components are similar in the proximal and distal segments, and lower than the corresponding values in rat colon; (2) amiloride sensitive apical Na conductances are absent in rat proximal colon, rat distal colon, and human proximal colon, but in human distal colon amiloride produces changes consistent with blockade of an apical Na conductance and inhibition of electrogenic Na transport; (3) a TEA-sensitive apical K conductance may be present in rat proximal colon (a K secretory epithelium), but not in rat distal colon (a K absorptive epithelium) or in either segment of human colon; and (4) in rat colon, replacement of mucosal and serosal Cl produces changes consistent with a substantial paracellular shunt permeability to Cl which is more marked in the proximal segment, whereas in human colon Cl replacement results in changes which suggest a relatively small paracellular shunt permeability to Cl which is similar in both segments. These data indicate marked segmental differences in Na, K and Cl transport in rat and human colon, and emphasise the hazards of applying models of colonic electrolyte transport in one species to another.

Adult↗