Electrolyte transport in the mammalian colon: mechanisms and implications for disease.

The colonic epithelium has both absorptive and secretory functions. The transport is characterized by a net absorption of NaCl, short-chain fatty acids (SCFA), and water, allowing extrusion of a feces with very little water and salt content. In addition, the epithelium does secret mucus, bicarbonate, and KCl. Polarized distribution of transport proteins in both luminal and basolateral membranes enables efficient salt transport in both directions, probably even within an individual cell. Meanwhile, most of the participating transport proteins have been identified, and their function has been studied in detail. Absorption of NaCl is a rather steady process that is controlled by steroid hormones regulating the expression of epithelial Na(+) channels (ENaC), the Na(+)-K(+)-ATPase, and additional modulating factors such as the serum- and glucocorticoid-regulated kinase SGK. Acute regulation of absorption may occur by a Na(+) feedback mechanism and the cystic fibrosis transmembrane conductance regulator (CFTR). Cl(-) secretion in the adult colon relies on luminal CFTR, which is a cAMP-regulated Cl(-) channel and a regulator of other transport proteins. As a consequence, mutations in CFTR result in both impaired Cl(-) secretion and enhanced Na(+) absorption in the colon of cystic fibrosis (CF) patients. Ca(2+)- and cAMP-activated basolateral K(+) channels support both secretion and absorption of electrolytes and work in concert with additional regulatory proteins, which determine their functional and pharmacological profile. Knowledge of the mechanisms of electrolyte transport in the colon enables the development of new strategies for the treatment of CF and secretory diarrhea. It will also lead to a better understanding of the pathophysiological events during inflammatory bowel disease and development of colonic carcinoma.     

Altered cryptal expression of luminal potassium (BK) channels in ulcerative colitis

Decreased sodium (Na(+)), chloride (Cl(-)), and water absorption, and increased potassium (K(+)) secretion, contribute to the pathogenesis of diarrhoea in ulcerative colitis. The cellular abnormalities underlying decreased Na(+) and Cl(-) absorption are becoming clearer, but the mechanism of increased K(+) secretion is unknown. Human colon is normally a K(+) secretory epithelium, making it likely that K(+) channels are expressed in the luminal (apical) membrane. Based on the assumption that these K(+) channels resembled the high conductance luminal K(+) (BK) channels previously identified in rat colon, we used molecular and patch clamp recording techniques to evaluate BK channel expression in normal and inflamed human colon, and the distribution and characteristics of these channels in normal colon. In normal colon, BK channel alpha-subunit protein was immunolocalized to surface cells and upper crypt cells. By contrast, in ulcerative colitis, although BK channel alpha-subunit protein expression was unchanged in surface cells, it extended along the entire crypt irrespective of whether the disease was active or quiescent. BK channel alpha-subunit protein and mRNA expression (evaluated by western blotting and real-time PCR, respectively) were similar in the normal ascending and sigmoid colon. Of the four possible beta-subunits (beta(1-4)), the beta(1)- and beta(3)-subunits were dominant. Voltage-dependent, barium-inhibitable, luminal K(+) channels with a unitary conductance of 214 pS were identified at low abundance in the luminal membrane of surface cells around the openings of sigmoid colonic crypts. We conclude that increased faecal K(+) losses in ulcerative colitis, and possibly other diseases associated with altered colonic K(+) transport, may reflect wider expression of luminal BK channels along the crypt axis.     

Effect of feeding a high protein diet on solute-coupled water absorption from rat colon

Using an in vivo sac technique, net transport of water, Na, Cl and K was studied in the colon ascendens of rats fed either a high carbohydrate (HC) or high protein (HP) diet, since water intake is elevated in HP-rats. The ligated colon sacs were filled with isotonic Krebs-Henseleit solution.Net Na and Cl absorption rates related to 1 g intestinal dry weight were 46% and 30% higher in HP-rats compared with HC-rats. Net water absorption in HP-rats exceeded that in HC-rats by 115%. Therefore the ratio between net water absorption and net absorption of solutes was higher in HP-rats than in HC-rats, and thus the hypertonicity of the absorbate was lower in the HP-rats. There was a net secretion of K in both groups of rats to about the same extent.Experiments with²²Na indicate that the increased net Na absorption in HP-rats was due to an increased unidirectional Na transport from the lumen to the blood side of the colon.The group difference in the ratio between net absorption of water and solutes might be a manifestation of regulatory mechanism controlling intestinal water absorption.Supported by the Deutsche Forschungsgemeinschaft     

Potential role of reduced basolateral potassium (IKCa3.1) channel expression in the pathogenesis of diarrhoea in ulcerative colitis

Diarrhoea in ulcerative colitis (UC) mainly reflects impaired colonic Na(+) and water absorption. Colonocyte membrane potential, an important determinant of electrogenic Na(+) absorption, is reduced in UC. Colonocyte potential is principally determined by basolateral IK (KCa3.1) channel activity. To determine whether reduced Na(+) absorption in UC might be associated with decreased IK channel expression and activity, we used molecular and patch clamp recording techniques to evaluate IK channels in colon from control patients and patients with active UC. In control patients, immunolabelling revealed basolateral IK channels distributed uniformly along the surface-crypt axis, with substantially decreased immunolabelling in patients with active UC, although IK mRNA levels measured by quantitative PCR were similar in both groups. Patch clamp analysis indicated that cell conductance was dominated by basolateral IK channels in control patients, but channel abundance and overall activity were reduced by 53% (p = 0.03) and 61% (p = 0.04), respectively, in patients with active UC. These changes resulted in a 75% (p = 0.003) decrease in the estimated basolateral membrane K(+) conductance in UC patients compared with controls. Levels of IK channel immunolabelling and activity in UC patients in clinical remission were similar to those in control patients. We conclude that a substantial decrease in basolateral IK channel expression and activity in active UC most likely explains the epithelial cell depolarization observed in this disease, and decreases the electrical driving force for electrogenic Na(+) transport, thereby impairing Na(+) absorption (and as a consequence, Cl(-) and water absorption) across the inflamed mucosa.     

Effects of methylprednisolone on electrolyte transport by in vitro rat ileum

Administration of the glucocorticoid methylprednisolone (MP) (30 mg/kg body wt for 3 days) to rats increased intestinal mucosal guanylate cyclase and Na-K-ATPase activities, short-circuit current (Isc), electrical potential difference (PD), net Na absorption, and net Cl secretion and reversed HCO3 transport from secretion to absorption. In the MP-treated animals, removal of HCO3 from both the mucosal and serosal bathing solutions increased Cl secretion but did not alter the Isc, PD, and net Na flux. Removal of Cl abolished the MP-induced increase in Isc but did not affect the MP-induced changes in net Na and HCO3 fluxes. At 6 h, after a single dose of MP, stimulation of guanylate cyclase activity was already maximal, whereas Na-K-ATPase activity was not detectably altered. The changes in intestinal transport properties present 6 h after MP treatment and associated with the increased guanylate cyclase activity were an increase in Isc and PD and a reversal of net Cl absorption to net secretion. These results suggest that an initial response to MP administration is a persistent increase in intestinal guanylate cyclase activity that mediates an electrogenic Cl secretory process, then is followed by a superimposed effect of increased Na-K-ATPase activity that mediates an increase in net Na absorption.     

The effect of aldosterone and the renin-angiotensin system on sodium, potassium and chloride transport by proximal and distal rat colon in vivo.

1. The roles of aldosterone and angiotensin in the direct control of epithelial sodium transport in vivo have been investigated by measurement of electrical p.d. changes and of the fluxes of sodium, potassium and chloride in rat colon, an organ actively involved in electrolyte homoeostasis. Exogenous angiotensin and aldosterone were given by both short- and long-term infusions and endogenous secretion of the hormones was varied by dietary sodium variation and by nephrectomy and/or adrenalectomy. 2. In vitro angiotensin has been shown to influence colonic salt and water absorption but in the present in vivo experiments administered angiotensin had no significant action on p.d. or on the ionic fluxes of the proximal or distal colon. The increase in p.d. produced by infusing aldosterone was unaffected by giving angiotensin concurrently. The effect of sodium depletion in stimulating sodium absorption and potassium secretion was completely abolished by adrenalectomy but was unaffected by nephrectomy. 3. During prolonged infusion of angiotensin into adrenalectomized rats, a small fall in faecal fluid and sodium content was observed, but this change would have little significance in sodium homoeostasis. 4. Aldosterone and sodium depletion stimulated sodium absorption in both proximal and distal colon but significant increase in potassium secretion was demonstrable only in the distal colon. Bicarbonate secretion (by calculation) was unaffected. In the proximal colon, the increased sodium absorption appeared to be accompanied by increased chloride absorption while in the distal colon it was principally the sodium-potassium exchange that was increased. 5. Adrenalectomy reduced potassium secretion in both proximal and distal colon but sodium absorption was only significantly reduced in the proximal colon. 6. It was concluded that there is no evidence that angiotensin in the living animal has a role as an important salt retaining hormone by direct epithelial action. Aldosterone has a considerable effect which is independent of the presence of angiotensin, and which differs in proximal and distal colon in regard to the relative effects on chloride absorption and potassium secretion.     

Transport of electrolytes across the helicoidal colon of the new-born pig.

1. The Na, K, Cl and water content of faeces removed from different parts of the pig helicoidal colon were determined for 1-day-old and adult animals. Faecal Na, Cl and water content fell in both cases during passage of contents through the colon. K content increased in the distal colon of the adult pig. This did not occur in the 1-day-old animal. 2. The colon of the 1-day-old pig removed a larger proportion of water from its contents than did that of the adult. The absorption of both water and Cl was found to extend into the distal colon of the 1-day-old animal; little or no net absorption took place in this region in the adult. 3. Colons taken from new-born pigs maintained stable short-circuit currents of about 60-80 muA cm-2 with open-circuit voltages of about 10 mV. Similar values were found for proximal and mid regions of colons taken from 1-day-old, suckled animals. In the distal colon, however, both short-circuit current and open-circuit potential doubled after suckling. 4. Measurements of Na flux in vitro showed no regional difference at birth. The amount of Na absorbed, about 4.5 muequiv cm-2 h-1, was twice that predicted from the short-circuit current, supposing that to be due solely to the electrogenic transport of Na. 5. Colons taken from suckled pigs transported Na at double the rate found in the new-born animal. This applied to both the proximal region, where the short-circuit current remained constant, and the distal region, where the short-circuit was double that of the new-born. 6. Fluxes of Cl and K were also measured across the proximal colon of the one-day-old, suckled pig. There was a net absorption of Cl and secretion of K (1.3 and -0.05 muequiv cm-2 h-1 respectively). These fluxes, taken together with that for Na, could not wholly account for the short-circuit current measured across these preparations. 7. The pig colon seems well able to cope with both electrolyte and water absorption during the first 24 hr of post-natal life. Part of the absorbed sodium appears to follow a non-electrogenic, possibly pinocytotic, route, but the full ionic contribution to the measured short circuit current has still to be determined.     

Ileal HCO3 secretion: relationship to Na and Cl transport and effect of theophylline.

Interrelationships among Na, Cl, and HCO3 transport processes were examined in short-circuited rabbit ileal mucosa. As serosal (HCO3) was increased from 10 to 50 mM (pH from 7.1 to 7.8), net Na absorption decreased from 4.6 to 0.3 mueq/h-cm2, net Cl flux changed from absorption of 0.9 to secretion of 0.9 and a net HCO3 secretion of 3.0 developed. A similar change in net Cl flux was also observed when serosal Pco2 was altered at constant (HCO3). In Cl-free SO4-Ringer, serosal alkalinization produced net HCO3 secretion which was not significantly less than that observed in Cl-containing Ringer. Theophylline caused secretory changes in net Na and Cl fluxes at both 10 and 50 mM serosal (HCO3). Theophylline did not alter net HCO3 flux in Cl-Ringer but increased net HCO3 flux in SO4-Ringer. Total dc conductance was decreased by both serosal alkalinization and theophylline. Shortcircuit current was consistently increased by theophylline but not by serosal alkalinization. The results indicate that ileal ion transport is regulated in part by serosal pH and/or (HCO3) and that resulting changes in Cl and HCO3 transport are coupled one-for-one with changes in Na transport. Furthermore, HCO3 secretion does not require the presence of Cl in the bathing medium.     

Ion transport by rabbit jejunum in vivo.

Net ion and H2O transport by jejunum adjacent to the ligament of Treitz (proximal jejunum) and midjejunum were measured in vivo by continuous perfusion with HCO3-Ringer solution containing a volume marker. Proximal jejunum secreted Na and H2O, whereas midjejunum absorbed Na and H2O. Both segments secreted CO2 and absorbed K and Cl. D-glucose stimulated absorption of Na and H2O and the transmural electrical potential difference (PD) in both segments, but these changes were not accompanied by alterations in Cl, CO2, or K fluxes. However, the increse in Na absorption caused by 3-O-methylglucose was matched by an increase in Cl absorption. This, in addition to increased tissue lactate concentration after addition of D-glucose, suggests that organic anion maintains electroneutrality for Na transport enhanced by D-glucose. Cholera toxin had no effect on ion transport or PD in proximal jejunum, but cholera toxin stimulated secretion and increased the PD in more distal jejunum. Although proximal jejunum shows spontaneous secretory activity, its capacity for secretion is not as great as more distal small intestine.     

The gradient of electrical potential difference and of sodium and potassium of the gut contents along the caecum and colon of normal and sodium-depleted rats

1. The Na, K and water content of stools, and of gut contents removed from the terminal ileum, caecum and colon were determined in normal and Na-depleted rats and the p.d. across the colon wall measured at the site of removal of each specimen.

2. During passage through the caecum and colon, especially the ascending segment of colon, the faecal Na and water content fell considerably, K content being unchanged in the normal rats and falling in the Na-depleted. Na concentration of the faecal water fell but K concentration rose owing to water absorption.

3. Feeding normal rats with a sulphonated polystyrene resin caused a considerable Na loss in the stool, the ratio Na/(Na+K) being consistently greater than in rats not taking resin. Resin induced little Na but much K loss in Na-depleted rats.

4. The electrical p.d. across the colon wall varied little over the length of the caecum and colon in normal rats, rarely exceeding 20 mV, the serosa being +ve with respect to lumen. Potential difference measurements were greater in Na-depleted rats, and those of the caecum and descending colon were consistently higher than those of the ascending colon. There was a similar pattern in resin-fed rats but potentials tended to be higher.

5. K concentration of the gut contents was always greater than could be accounted for if K were passively distributed across the colonic mucosa.

6. It was concluded that: (i) active Na absorption was stimulated by Na depletion; (ii) K was probably actively transported into the colon lumen, and when unabsorbable anions were present in the gut K secretion was critically important in Na absorption; (iii) the elevation of p.d. associated with Na depletion was probably associated with the stimulated Na transport.

     

cGMP modulation of ileal ion transport: in vitro effects of Escherichia coli heat-stable enterotoxin

Diarrheagenic strains of Escherichia coli have been shown to produce a heat-stable enterotoxin (ST) that simulates guanylate cyclase, increases short-circuit current (Isc), and inhibits active Cl absorption in the intestine. In rabbit ileum, the ion transport effects are smaller than those produced by cAMP-related agonists. Because ST may be a selective cGMP agonist, we further explored its mode of action in rabbit ileum. ST inhibits net Na and net Cl absorption. ST also inhibits the same fraction of Cl influx across the brush border that theophylline inhibits. At maximal doses, ST and 8-bromo-cGMP (8-Br-cGMP) had nearly equal, nonadditive effects of Isc that were about 66% of that produced by 8-Br-cAMP. ST increased mucosal cGMP concentration 16-fold, whereas epinephrine, an inhibitor of secretion, increased cGMP concentration by only 30%. This is insufficient to alter ion transport because doses of ST that increased cGMP concentration by 100% failed to alter Cl fluxes. Furthermore, epinephrine did not increase cGMP concentration in isolated enterocytes. We conclude that 1) cGMP mediates ST effects on ion transport, and 2) although ST and cAMP-related agonists have the same antiabsorptive effects, ST is less effective in stimulating electrogenic Cl secretion.     

Aldosterone low-dose,short-term action in adrenalectomized glucocorticoid-substituted rats: Na,K, Cl,HCO3, osmolyte,and water transport in proximal and rectal colon

The short-term action of aldosterone in physiological concentration on net fluxes of Na, K, Cl, HCO₃, osmolytes, and water was examined in the proximal colon and rectal colon of adrenalectomized (ADX) rats in vivo. The measuring time was 12 h, divided in eight periods of 90 min. (a) Aldosterone alone (6 nmol h^–1kg^–1) did not stimulate transport in ADX rats. In these experiments plasma [K] increased to fatal values. A basal glucocorticoid substitution of 24 nmol h^–1kg^–1 corticosterone caused plasma K to stay constant throughout the experiment, so that epithelial transport was not handicapped by non-specific effects of ADX, but this also did not restore the decreased transport of ADX rats to control values. Under these conditions (absence of aldosterone) in the rectal colon Na and H₂O transport was zero, whereas in the proximal colon flux rates were depressed by between 30% and 50%. In contrast, basal glucocorticoid substitution of 18 nmol h^–1kg^–1 corticoster-one plus infusion of 6 nmol h^–1kg^–1 aldosterone caused transport stimulation to values not significantly different from those of non-ADX controls.We conclude that after ADX, aldosterone at physiological concentrations increases transport if, as a prerequisite, a basal glucocorticoid substitution is provided. Transport of Na, K, and H₂O is under the total control of aldosterone in the rectal colon but is only moderately altered in the proximal colon. (b) In the proximal colon aldosterone is effective on electroneutral Na transport consistent with the Na/H, Cl/HCO₃ double exchanger, while in the rectal colon aldosterone controls the amiloride-sensitive Na channel, which is the sole apical Na transporter in that segment. In this respect the rectal colon is functionally distinct from the distal colon of other studies in the rat, where under unstimulated conditions the double exchanger is present. Regarding Na transport mechanisms, the rat large intestine thus consists of three distinct segments, the proximal, distal, and rectal colon. (c) In the rectal, but not the proximal colon, active net K absorption against the electrochemical gradient took place in the absence of aldosterone, but was suppressed in its presence. (d) The flux ratio of osmolytes over H₂O was constantly hypertonic as compared to the plasma (387±1 mosmol l^–1), independent of absolute flux size, the colonic segment examined, or the steroid concentration used. This effect may be due to a hypertonic unstirred layer within the lamina propria.Jx, transepithelial net flux of x, negative sign denotes secretion; ^ms transepithelial voltage, negative sign indicates luminal negativity     

Mechanism of calcium ionophore stimulated Cl secretion from frog skin glands

The aim of the present study was to investigate the mechanism by which the calcium ionophore A23187 stimulates Cl and water secretion from exocrine glands in the frog skin. The Cl secretion was visualized as changes in short-circuit current (SCC) in skins where the Na absorption was blocked by amiloride applied to the apical membrane. Measurements of A23187 stimulated ion fluxes showed that the ionophore induced a net secretion of Cl, Na and K. The active Cl secretion was enhanced more than the Na and K secretion, resulting in a net secretion of negative ions which closely resembled the A23187-stimulated SCC. The effect of A23187 was abolished in skins pretreated with indomethacin, implying the involvement of prostaglandins in the response. Furthermore, the effect of A23187 was inhibited in the presence of quinacrine, indicating that the activation of the cyclooxygenase pathway is dependent on phospholipase A₂ activity. In addition, the A23187, but not the arachidonic acid stimulated Cl secretion was abolished in the presence of trifluoperazine, suggesting that the effect of the ionophore may be mediated via a Ca²⁺-calmodulin-dependent step located before the activation of the cyclooxygenase. The net water flow and the Cl secretion were measured simultaneously under the conditions outlined above. The stimulation, inhibition, and time-course of the water secretion were similar to the changes observed for the Cl secretion. The A23187 stimulated Cl secretion was enhanced by the phosphodiesterase inhibitor, theophyllin, indicating that the effect of A23187 was caused by an increase in the intracellular cAMP level in the gland cells. From the present data it is suggested that the calcium ionophore stimulates the Cl and water secretion from frog skin gland not by a direct effect of Ca²⁺-ions per se, but in an indirect manner by stimulating the prostaglandin synthesis, which probably results in an increase in the cAMP level in the gland cells.     

Absorption and secretion of potassium by rabbit descending colon

Measurements of K fluxes under a variety of conditions have provided an internally consistent set of data that demonstrate active absorption and active secretion of K by rabbit descending colon in vitro. The properties of K diffusion across the paracellular pathway are those of a free solution shunt. With Na and Cl present on both sides of short-circuited tissues the two opposing active K transport systems balance each other, so that there is no net K transport. Net K absorption results when the transcellular secretory K flux is inhibited by 1. serosal addition of ouabain, 2. serosal addition of furosemide, or 3. omission of either Na or Cl from the serosal solution. Hence basolateral K uptake appears to be mediated by a furosemide-sensitive Na–Cl–K cotransport system in addition to the Na–K exchange pump. Luminal addition of mersalyl or orthovanadate inhibits active K absorption. The adenosine analogue 5-N-ethylcarboxamide adenosine and the -adrenergic agent isoproterenol, added to the serosal solution, cause net K secretion which is inhibitable by furosemide. The secretory K fluxes, both under stimulated and non-stimulated conditions, are abolished by an opposing electrical gradient, suggesting conductive K exit across the apical cell membrane, whereas K absorption appears to be an electroneutral process.     

Water and ion transport by the urinary bladder of the teleost Pseudopleuronectes americanus.

Water and ion transport by the isolated teleost urinary bladder were studied. The transepithelial electrical PD across sac-type bladder preparations was unstable, i.e., initially mucosa positive but becoming more negative with time. Perfused bladders maintained a low mucosa positive PD which was stable. Both Na and Cl appeared to be actively transported from mucosal side (M) to serosal side (S). Voltage clamping the bladder at 0, -50, or +50 mV had almost no effect on active or passive Na or Cl flux in either direction. Na and Cl transport seemed electrically neutral. Fluid absorption (M to S) was directly correlated with absorption of osmotically active solutes. These solutes were almost all Na and Cl. The bladder acidified and secreted K+ into the mucosal fluid. Divalent ions were concentrated in the mucosal fluid as a result of fluid absorption. Although furosemide and ethacrynic acid inhibited ion and water transport by the bladder, ouabain was effective at a much lower concentration. Ouabain (10(-4) M) inhibited active Na transport when applied only to the mucosal or only to the serosal surface. Ouabain abolished the PD only from the serosal surface.     

Effect of acetazolamide on sodium and chloride transport by in vitro rabbit ileum.

Acetazolamide (8 mM) aboishes active Cl absorption and inhibits but does not abolish active Na absorption by stripped, short-circuited rabbit ileum. These effects are not accompanied by significant changes in the transmural electrical potential difference or short-circuit current. Studies of the undirectional influxes of Na andCl indicate that acetazolamide inhibits the neutral, coupled NaCl influx process at the mucosal membranes. This action appears to explain the observed effect of acetazolamide on active, transepithelial Na and Cl transport. Acetazolamide did not significantly inhibit either spontaneous or theophylline-induced Cl secretion by this preparation, suggesting that the theophylline-induced secretion may not simply be due tothe unmasking of a preexisting efflux process when the neutral influx mechanism is inhibited by theophylline. Finally, inhibition of the neutral NaCl influx process by acetazolamide does not appear to be attributable to an inhibition of endogenous HCO3production or an elevation in intracellular cyclic-AMP levels. Instead, it appearstheat the effect of acetazolamide is due to a direct interaction with a membrane component involved in the coupled influx process.     

Comparison of transport mechanisms in isolated ascending and descending rat colon.

The mechanisms of water and ion transport in ascending and descending rat colon were compared using an everted open mucosal sac preparation. Net water flux, measured gravimetrically, was similar in both segments (15.3 plus or minus 1.2 and 13.7 plus or minus 1.3mul h(-1) mg(-1), NS). Net catonic flux J(Na+K),net anionic flux J(Cl-HCO3), and net solute flux Josm were also similar; but the constituents of these flux , namely JNA, JK, and JHCO3, were significantly different. The descending colon absorbed significantly less Na and secreted significantly more HCO3. Only the descending colon absorbed K, whereas net JK across the ascending colon was zero. The PD across either segment ranged from 3 to 7 mV, mucosal side negative. Consideration of net flux and electrochemical gradient indicated that in both segments Na was absorbed actively. The nature of Cl transport could not be ascertained. Assuming transmural movement, HCO3 was secreted (or H ion absorbed) actively. Only the descending colon absorbed K actively. Across the ascending colon K was distributed close to electrochemical equilibrium.The compostion of the absorbates was calculated from Ji/Jv after correction of Jv for filtered water. Both absorbates were equally hypertonic (448.5 plus orminus 9.3 and 421.7 plus or minus 13.2; NS.)The ascending colon absorbate contained a significantly higher Na concentration and no K. The descending colon absorbate contained 15 mM K, about 3 times the K concentration in the bathing solution. It was concluded that the ascending colon and descending colon displayed quantitative differences in Na absorption and HCO3 secretion and a qualitative difference in K transport.     

Ion and liquid transport across the bronchiolar epithelium

The proper homeostasis of the airway surface liquid (ASL) depends on transepithelial ion and fluid transport and is critically important for lung defence, and more specifically for mucociliary transport. In cystic fibrosis (CF), abnormal ion and fluid transport lead to depleted ASL volume resulting in mucus plugs and recurrent lung infections. Like bronchi, human bronchioles exhibit amiloride-sensitive Na(+) absorption and cyclic-AMP and Ca(2+)-activated Cl(-) secretion. However, cyclic-AMP-stimulated Cl(-) and fluid secretion appears to be quantitatively more important in bronchioles than in bronchi. In CF bronchioles, like in CF bronchi, the ASL height is reduced because of an abnormally persistent Na(+) absorption, combined with a lacking CFTR-dependent Cl(-) secretion. The precocity and severity of the bronchiolar disease in CF could be attributed in part to the more important role of CFTR-dependent Cl(-) secretion and fluid secretion, and the lack of compensatory ATP-driven Cl(-) secretion and fluid secretion, in bronchioles compared to bronchi.     

Chloroquine stimulates absorption and inhibits secretion of ileal water and electrolytes

The effects of chloroquine diphosphate, a drug with "'membrane-stabilizing" properties, were studied on basal ileal absorption and on ileal secretion induced by increased intracellular cAMP levels and calcium (serotonin). The studies were performed on rat (in vivo) and rabbit ileum (in vitro). Intraluminal chloroquine (10(-4) M) reversed cholera toxin- and theophylline-induced secretion in rat ileum but did not alter the cholera toxin- and theophylline-induced increases in cAMP content. Addition of chloroquine (10(-4) M) to the mucosal surface of rabbit ileum did not alter basal active electrolyte transport or the serotonin-induced decreased Na and Cl absorption but inhibited the theophylline-induced C1 secretion. Addition of chloroquine (10(-4)) M) to the serosal surface stimulated net Na and Cl absorption. This effect may involve intracellular calcium. Chloroquine increased the rabbit ileal calcium content and decreased 45Ca2+ influx from the serosal surface. Both the mucosal and serosal effects of chloroquine described led to a net increase in absorptive function of the intestine and should prove useful in developing treatment of diarrheal diseases.     

Localization of Ca2+ -activated big-conductance K+ channels in rabbit distal colon

Big-conductance Ca(2+)-activated K(+) channels (BK channels) may play an important role in the regulation of epithelial salt and water transport, but little is known about the expression level and the precise localization of BK channels in epithelia. The aim of the present study was to quantify and localize the BK channels in the distal colon epithelium by iberiotoxin (IbTX) binding using the radiolabeled iberiotoxin analogue (125)I-IbTX-D19Y/Y36F, by autoradiography and by immunohistochemical studies. The results showed that the surface cells, responsible for Na(+) absorption, contained a high number of BK channels, whereas the abundance of the channels in the Cl(-)-secreting crypt cells was very low or absent. Surprisingly, the (125)I-IbTX-D19Y/Y36F binding and immunohistochemical studies showed expression of BK channels in the apical as well as in the basolateral membranes of the surface cells. In conclusion, the significant and distinct expression of BK channels in epithelia, combined with their strict regulation, indicate that these channels may play an important role in the overall regulation of salt and water transport.