Rate Of Bicarbonate Secretion Research Articles

Intestinal response to ocean acidification in the European sea bass (Dicentrarchus labrax)

The intestine of marine fishes contributes to the ocean carbon cycle producing carbonate aggregates as part of the osmoregulatory process. Therefore, this study aimed to evaluate physiological adjustments of European sea bass (Dicentrarchus labrax) intestine to a higher pCO2 environment likely in the near future (~1700 μatm). At the whole-body level, hypercapnia for 5 weeks resulted in fish having a significantly diminished specific growth rate, condition factor and hepatosomatic index. An increase in plasma osmolality and HCO3− concentration was detected, paralleled by decreased metabolites concentrations. In the intestine, high seawater pCO2 was without effect on ouabain-sensitive ATPase activities, while Bafilomycin A1-sensitive ATPase activity significantly decreased in the anterior intestine. Anterior and mid intestine were mounted in Ussing chambers in order to measure bioelectrical parameters and bicarbonate secretion by pH-Stat ex-vivo. Hypercapnia induced a 2.3 and 2.8-fold increase in bicarbonate secretion rates in the anterior and mid intestine, respectively. In the intestinal fluid, HCO3− concentration increased 2.2-fold, and carbonate precipitates showed a 4.4-fold increase in response to hypercapnia, paralleled by a >3-fold increase of drinking and a >2-fold increase of intestinal volume at any given time. At the molecular level, hypercapnia elicited higher intestinal mRNA expression levels for atp6v1b (V-ATPase B subunit), slc4a4, slc26a3, and slc26a6, both in the anterior and mid intestine. As a whole, our results show that the intestine of sea bass responds to high seawater pCO2, a response that comes at a cost at the whole-body level with an impact in the fish specific growth rate, condition factor, and hepatosomatic index.

Mass Transport Analysis of the Enhanced Buffer Capacity of the Bicarbonate–CO2 Buffer in a Phase-Heterogenous System: Physiological and Pharmaceutical Significance

The bicarbonate buffer capacity is usually considered in a phase-homogeneous system, at equilibrium, with no CO2 transfer between the liquid buffer phase and another phase. However, typically, an in vitro bicarbonate buffer-based system is a phase-heterogeneous system, as it entails continuously sparging (bubbling) the dissolution medium with CO2 in a gas mixture, at constant ratio, to maintain a constant partial pressure of CO2(g) and CO2(aq) molarity at a prescribed value, with CO2 diffusing freely between the gas and the aqueous phases. The human gastrointestinal tract is also a phase-heterogeneous system, with CO2 diffusing across the mucosal membrane into the mesenteric arterial blood, which serves as a sink for CO2 from the intestinal lumen. In this report, a mass transport analysis of the apparent buffer capacity of a phase-heterogeneous bicarbonate-CO2 system is developed. It is shown that, most significantly, a phase-heterogeneous bicarbonate-CO2 system can have a much higher buffer capacity than a phase-homogeneous system such that the buffer capacity is dependent on the bicarbonate concentration. It is double that of a phase-homogeneous system at the pH = p Ka for a monoprotic buffer at the same concentration. This buffer capacity enhancement increases hyperbolically with pH above the p Ka, thus providing a much stronger buffering to keep the pH in the physiologically neutral range. The buffer capacity will be dependent on the bicarbonate molarity (which in vivo will depend on the bicarbonate secretion rate) and not the pH of the luminal fluid. Further, there is no conjugate acid accumulation as a result of bicarbonate neutralization, since the resulting carbonic acid (H2CO3) rapidly dehydrates producing CO2 and H2O. The mass transport analysis developed in this report is further supported by in vitro experimental results. This enhanced bicarbonate buffer capacity in a phase-heterogeneous system is of physiological significance as well as significant for the dissolution and absorption of ionizable drugs.

High rates of intestinal bicarbonate secretion in seawater tilapia (Oreochromis mossambicus)

Osmoregulation in fish is a complex process that requires the orchestrated cooperation of many tissues. In fish facing hyperosmotic environments, the intestinal absorption of some monovalent ions and the secretion of bicarbonate are key processes to favor water absorption. In the present study, we showed that bicarbonate levels in the intestinal fluid are several fold higher in seawater than in freshwater acclimated tilapia (Oreochromis mossambicus). In addition, we analyzed gene expression of the main molecular mechanisms involved in HCO3– movements i.e. slc26a6, slc26a3, slc4a4 and v-type H-ATPase sub C in the intestine of tilapia acclimated to both seawater and freshwater. Our results show an anterior/posterior functional regionalization of the intestine in tilapia in terms of expression patterns, which is affected by environmental salinity mostly in the anterior and mid intestine. Analysis of bicarbonate secretion using pH-Stat in tissues mounted in Ussing chambers reveals high rates of bicarbonate secretion in tilapia acclimated to seawater from anterior intestine to rectum ranging between ~900 and ~1700nmolHCO3–cm−2h−1. However, a relationship between the expression of slc26a6, slc26a3, slc4a4 and the rate of bicarbonate secretion seems to be compromised in the rectum. In this region, the low expression of the bicarbonate transporters could not explain the high bicarbonate secretion rates here described. However, we postulate that the elevated v-type H-ATPase mRNA expression in the rectum could be involved in this process.

Temperature Modulates the Effects of Ocean Acidification on Intestinal Ion Transport in Atlantic Cod, Gadus morhua

CO2-driven seawater acidification has been demonstrated to enhance intestinal bicarbonate secretion rates in teleosts, leading to an increased release of CaCO3 under simulated ocean acidification scenarios. In this study, we investigated if increasing CO2 levels stimulate the intestinal acid–base regulatory machinery of Atlantic cod (Gadus morhua) and whether temperatures at the upper limit of thermal tolerance stimulate or counteract ion regulatory capacities. Juvenile G. morhua were acclimated for 4 weeks to three CO2 levels (550, 1200, and 2200 μatm) covering present and near-future natural variability, at optimum (10°C) and summer maximum temperature (18°C), respectively. Immunohistochemical analyses revealed the subcellular localization of ion transporters, including Na+/K+-ATPase (NKA), Na+/H+-exchanger 3 (NHE3), Na+/ cotransporter (NBC1), pendrin-like Cl−/ exchanger (SLC26a6), V-type H+-ATPase subunit a (VHA), and Cl− channel 3 (CLC3) in epithelial cells of the anterior intestine. At 10°C, proteins and mRNA were generally up-regulated for most transporters in the intestinal epithelium after acclimation to higher CO2 levels. This supports recent findings demonstrating increased intestinal secretion rates in response to CO2 induced seawater acidification. At 18°C, mRNA expression and protein concentrations of most ion transporters remained unchanged or were even decreased, suggesting thermal compensation. This response may be energetically favorable to retain blood levels to stabilize pHe, but may negatively affect intestinal salt and water resorption of marine teleosts in future oceans.

Exploration of Intestinal Calcium Precipitation as a Barrier to Absorption at High Calcium Doses

To investigate the hypothesis that intestinal bicarbonate secretions precipitate calcium as the carbonate salt, thereby resulting in poor absorption (20-40%) from calcium supplements. The in vitro effect of calcium dose and bicarbonate secretion rate on soluble calcium was determined by neutralizing elemental Ca(2+)(250, 475, and 630 mg) in 0.1 N HCl to pH 7 with a bicarbonate secretion rate of 0.12 or 1.2 mEq/min. P (CO2) and pH of the solutions were monitored. Soluble calcium was analyzed using atomic absorption spectrometry. Additionally, the transport of calcium across Caco-2 cell monolayers was determined. Calcium from a 250 mg dose remained soluble during bicarbonate secretion, regardless of rate. Once the dose increased, the calcium remaining in solution decreased during neutralization with bicarbonate. The Ca(2+)/CaHCO(3) (+) ratio had no effect on calcium permeation across Caco-2 cell monolayers. The physicochemical mechanism of intestinal calcium precipitation supports published clinical data by suggesting that once the solubility product of calcium carbonate is reached, increasing the calcium dose results in significant precipitation at intestinal pH values.

Higher proximal duodenal mucosal bicarbonate secretion is independent of Brunner's glands in rats and rabbits

Background & Aims : Duodenal bicarbonate secretion is impaired in patients with duodenal ulcer. Before characterization of any cellular transport defect is possible, the origin of duodenal bicarbonate (epithelial cells and/or Brunner's glands) must be determined. The aim of this study was to determine the role of Brunner's glands in duodenal bicarbonate secretion. Methods : Rats, which have Brunner's glands only in the proximal duodenum, and rabbits, which have Brunner's glands throughout the duodenum, were anesthetized. Basal and stimulated (with HCl, prostaglandin E 2, and vasoactive intestinal polypeptide [VIP]) bicarbonate secretion was measured in three isolated intestinal segments: proximal duodenum, distal duodenum, and proximal jejunum. Mucosal surface area and Brunner's gland thickness was quantitated in each segment. Results : Secretion rates in proximal and distal duodenum and proximal jejunum were significantly different. Normalized proximal-to-distal duodenal gradients in bicarbonate secretion were similar in the two species despite significantly different gradients of Brunner's gland thickness. In rabbits, gradients of bicarbonate secretion and Brunner's gland thickness were not correlated. In both species, HCl, prostaglandin E 2, and VIP stimulated secretion in all three segments. If the agonists specifically stimulated Brunner's gland bicarbonate secretion, relationships between gradients of bicarbonate secretion and Brunner's gland thickness would have been anticipated. This was not observed. Conclusions : The higher rates of bicarbonate secretion in the proximal duodenum than in the distal duodenum and proximal jejunum are independent of Brunner's glands.

Effect of amiloride on sodium transport in the proximal, distal, and entire human colonin vivo

In vitro studies under short-circuited conditions suggest that amiloride, a diuretic agent which is thought to block apical membrane sodium entry, has significant effects on sodium absorption by the human colon. To evaluate this in vivo, we studied the effect of amiloride applied in concentrations of 10(-5) and 10(-4) M on sodium transport and potential difference (PD) in human colon during steady-state perfusion. Net sodium absorption was reduced 25% by amiloride and chloride absorption by 15%; potassium and bicarbonate secretion rates were enhanced. In other studies the colon was divided into a proximal and distal test segment by endoscopic introduction of a collection channel to the descending colon-sigmoid junction. Comparison of tritiated water absorption by the two segments indicated that the distal segment comprised approximately 20% of the total colon surface area. However, the distal test segment only accounted for 5-7% of total sodium, chloride, or water absorption; in contrast, 17-20% of total potassium or bicarbonate secretion occurred there. In the proximal test segment, amiloride reduced net sodium absorption by almost one third from 21.0 to 14.4 mmol/hr (P less than 0.02) but had no significant effect on PD. In the distal test segment, amiloride produced a 25% reduction in mean sodium absorption from 1.2 to 0.9 mmol/hr, but this reduction was not statistically significant; however, potential difference was significantly reduced by 33% (P less than 0.02). These results suggest that most sodium absorption in normal human colon in vivo is mediated by transport processes which are insensitive to these doses of amiloride.(ABSTRACT TRUNCATED AT 250 WORDS)

Impaired pancreatico-biliary response to vagal stimulation and to cholecystokinin in human obesity

We previously found that massively obese patients respond with less gastric acid secretion in response to vagal stimulation. This is compatible with the described association between experimental obesity and altered vagal function in the rat. To confirm this observation, the pancreatic and biliary responses to vagal stimulation were examined in nine nondiabetic obese patients against a background secretin infusion of 15 CU × h −1, and monitored after a subsequent injection of 75 IDU of cholecystokinin. Two separate marker perfusion systems were used in the stomach and duodenum, respectively, and blood samples were drawn for hormone analyses. In contrast to controls having normal body weight, the obese patients failed to respond with increments of pancreatic enzyme secretion and duodenal bile acids after stimulation with modified sham feeding. Cholecystokinin stimulated the pancreatic secretion of trypsin, amylase, and lipase, the emptying of bile acids, and the release of gastrin, but the patients' responses were only half that of the controls. In the resting state the obese had higher outputs of bile and pancreatic enzymes and higher plasma levels of pancreatic polypeptide compared with controls, but the pancreatic bicarbonate secretion rate was not different. The almost complete suppression of the basal gastric acid secretion by a low dose of intravenous (IV) secretin in controls did not occur in the obese. We conclude that massive obesity is associated with a reduced pancreatic and biliary response to vagal stimulation. Compared with controls, the digestive functions of the obese patients seem to be less sensitive to stimulation by exogenous cholecystokinin. In addition, the normal release pattern of digestive hormones in the resting state and after stimulations showed multiple alterations in massive obesity.

HCO3- secretion in rat duodenum after treatment with omeprazole and ranitidine.

The bicarbonate secretion by the duodenal mucosa, which is stimulated by luminal acid, is very probably important in mucosal protection against the acid. It was of interest to investigate whether long-term deprivation of the mucosa of this acid stimulus affected the alkali secretion. Sprague-Dawley rats were treated for 4-6 weeks with either omeprazole, 14 mg/kg body weight twice daily, or ranitidine, 300 mg/kg twice daily, by means of gastric intubation. The rate of bicarbonate secretion by the duodenal mucosa was determined in situ by continuous titration. Neither the basal secretion nor the increase in secretion in response to stimulation by prostaglandin E2 or luminal acid (pH 2.0 for 5 or 60 min) differed in treated animals from that in controls that had received placebo (p greater than 0.05). Thus, 4-6 weeks of treatment with omeprazole or ranitidine did not reduce duodenal mucosal bicarbonate secretion in the rat, nor did these drugs diminish the ability of this mucosa to respond to prolonged luminal acidification or luminally administered prostaglandin E2.

Ammonia and bicarbonate transport by rat cortical collecting ducts perfused in vitro.

We measured bicarbonate and ammonia transport by isolated perfused cortical collecting ducts from deoxycorticosterone-treated rats. With no ammonia in the perfusate and bath solutions, the collecting ducts secreted bicarbonate. The bicarbonate secretion was prevented when the rats were given 40 mM NH4Cl to drink. When 4 mM total ammonia was added to the perfusate and bath, the collecting ducts secreted ammonia and the direction of bicarbonate transport reversed toward absorption. Under those conditions the collected total ammonia concentration exceeded the value predicted by the diffusion-trapping model, assuming pH equilibrium. However, when carbonic anhydrase was added to the perfusate (to assure pH equilibrium), the collected total ammonia concentration decreased to the level predicted by the diffusion-trapping model. We conclude that rat cortical collecting ducts can secrete bicarbonate at substantial rates; the rate of bicarbonate secretion is modified by changes in the acid-base intake of the rats; ammonia secretion occurs by simple nonionic diffusion in this segment; the ammonia secretion is enhanced by the presence of acidic pH disequilibrium in the lumen; and ammonia in the perfusion and bath solutions inhibits bicarbonate secretion by rat cortical collecting ducts, a response that may be important for the regulation of renal bicarbonate excretion.

Bicarbonate secretion and chloride absorption by rabbit cortical collecting ducts. Role of chloride/bicarbonate exchange.

Cortical collecting ducts (CCD) from rabbits treated with deoxycorticosterone (DOC) actively secrete bicarbonate at high rates. To investigate the mechanism of bicarbonate secretion, we measured bicarbonate and chloride transport in CCD from rabbits treated with DOC for 9-24 d. Removal of chloride (replaced with gluconate) from both perfusate and bath inhibited bicarbonate secretion without changing transepithelial voltage. Removal of chloride only from the bath increased bicarbonate secretion, while removal of chloride only from the perfusate inhibited secretion. In contrast to the effect of removing chloride, removal of sodium from both the perfusate and bath (replacement with N-methyl-D-glucamine) did not change the rate of bicarbonate secretion. The rate of bicarbonate secretion equaled the rate of chloride absorption in tubules bathed with 0.1 mM ouabain to inhibit any cation-dependent chloride transport. Under these conditions, chloride absorption occurred against an electrochemical gradient. Removal of bicarbonate from both the perfusate and bath inhibited chloride absorption. Removal of bicarbonate only from the bath inhibited chloride absorption, while removal of bicarbonate from the lumen stimulated chloride absorption. We conclude that CCD from DOC-treated rabbits actively secrete bicarbonate and actively absorb chloride by an electroneutral mechanism involving 1:1 chloride/bicarbonate exchange. The process is independent of sodium.

Vagal stimulation of human gastric bicarbonate secretion

Gastric bicarbonate secretion in humans was determined in vivo by using a gastric perfusion-aspiration system. A computer calculated the bicarbonate concentration every 30 s throughout the experiment from measurements of the pH and Pco2 in the aspirate. The total bicarbonate concentration was calculated according to the formula of Henderson and Hasselbalch as the sum of free bicarbonate plus the CO2 that was formed during reaction of bicarbonate with hydrogen ions. In 16 subjects basal gastric bicarbonate secretion was 410 ± 39 μmol/h (mean ± SEM). After sham feeding using the chew and spit technique to achieve physiologic vagal activation, the gastric bicarbonate secretion rate increased to 692 ± 67 μmol/h (p < 0.001). This response of bicarbonate secretion rate to vagal stimulation was independent of the intragastric pH (range 2–7). In 6 subjects the sham-feeding response was almost abolished (88% inhibition) by the anticholinergic drug benzilonium bromide, however, it was unaffected by premedication with indomethacin, The findings demonstrate that the increase in gastric bicarbonate secretion during the cephalic phase of gastric secretion occurs parallel to the increase in acid secretion. It may therefore be regarded as a physiologic response to reinforce the protective mucus-bicarbonate barrier. The response to vagal stimulation seems to be mediated by a muscarinic transmitter and to be independent of intragastric pH and endogenous prostaglandins.

Deoxycorticosterone-stimulated bicarbonate secretion in rabbit cortical collecting ducts: effects of luminal chloride removal and in vivo acid loading.

To assess the role of cortical collecting duct bicarbonate secretion in the regulation of net acid excretion, we have sought to identify what factors influence the secretion rate. Net and unidirectional bicarbonate fluxes were measured in isolated perfused cortical collecting ducts from deoxycorticosterone-treated rabbits. The collecting ducts secreted bicarbonate at 11-24 pmol X mm-1 X min-1, confirming the high rate seen in earlier studies. Oral acid loading (50 mM NH4Cl drinking water) completely inhibited the net bicarbonate secretion. The bath-to-lumen flux was markedly reduced with acid loading, but the lumen-to-bath flux changed very little. In tubules from rabbits treated with deoxycorticosterone (but not NH4Cl), luminal chloride replacement with either sulfate or gluconate completely and reversibly inhibited the net bicarbonate secretion. The bath-to-lumen flux was greatly inhibited, but there was little change in the lumen-to-bath flux. We conclude: 1) High rates of bicarbonate secretion can be induced in rabbit cortical collecting ducts by chronic treatment of the animals with deoxycorticosterone. 2) When deoxycorticosterone-treated rabbits were made acidotic by oral administration of NH4Cl, the bicarbonate secretion was prevented, indicating that the systemic acid-base state of the animal may be an important factor regulating bicarbonate secretion. 3) Replacement of chloride in the lumen with sulfate inhibits bicarbonate secretion in the cortical collecting duct, an effect which may explain in part the decrease in urinary pH in response to sulfate infusions in mineralocorticoid-stimulated animals.

Gastric Bicarbonate Secretion in Patients With Duodenal Ulcer

The gastric mucosa secretes both acid and bicarbonate. In patients with duodenal ulcers, gastric acid hypersecretion is well-established. However, gastric bicarbonate secretion rates in these patients have not been reported. Accordingly, we calculated gastric acid and bicarbonate secretion rates in 13 patients with duodenal ulcer and 13 healthy subjects (controls) using a recently validated method that uses measurements of gastric juice volume, acidity (hydrogen-ion concentration), and osmolality. Non-parietal and parietal gastric volume secretion were also calculated. Although ulcer patients secreted significantly more acid than controls under basal conditions and during a submaximal intravenous pentagastrin infusion, they secreted similar amounts of bicarbonate. Ulcer patients secreted significantly more parietal and nonparietal fluid than controls. Increased nonparietal secretions in duodenal ulcer patients diluted excessive, acidic parietal secretions, preventing significant differences in gastric acidity in ulcer patients and control subjects (50.1 +/- 8.7 vs. 44.0 +/- 9.7 mmol/L basally; 111.0 +/- 3.1 vs. 102.4 +/- 7.5 mmol/L during pentagastrin infusion, respectively). These studies indicate that gastric bicarbonate secretion is close to normal in patients with duodenal ulcer, whereas acid secretion from parietal cells and nonparietal volume secretion are greater than normal.

A comparative study of bicarbonate secretion by ileum and colon of Oryctolagus cuniculus. Influence of caecal pH

1. 1. The influence of caecal pH on movements of bicarbonate ion in rabbit colon and ileum has been studied. 2. 2. A net secretion of bicarbonate is noted in both intestinal segments (at higher rates in colon than in ileum) in our experimental conditions. 3. 3. The bicarbonate secretion rate is lowered when bicarbonate is added to caecum. 4. 4. The introduction of acetic acid at caecal level increased bicarbonate secretion rate both in ileum as in colon.

Effect of ouabain on Na,K-ATPase and electrolyte transport in the dog ileum in vivo.

It is currently believed that the rate and direction of sodium transport in the small intestine may be regulated by the activity of Na,K-ATPase in the basolateral cell membrane. We tested this hypothesis by selectively infusing ouabain, a known inhibitor of Na,K-ATPase, into the mesenteric artery supplying a perfused loop of ileum in 18 dogs. Before ouabain infusion there were significant correlations between the activity of Na,K-ATPase and net and lumen to plasma fluxes of sodium and chloride. After ouabain, there was no significant change in sodium and chloride transport, unidirectional fluxes or transmucosal potential difference, despite a 50% reduction in Na,K-ATPase activity. Furthermore, there was no significant correlation between Na,K-ATPase activity and sodium or chloride transport after ouabain. The only statistically significant effect of ouabain infusion was a reduction in the rate of bicarbonate secretion. Thus, the results of our experiments suggest that mucosal Na,K-ATPase is not a rate-limiting step in the absorption of sodium and chloride in the dog ileum, though it may be an important facilitative factor.

Effects of saline infusion and acute metabolic acidosis and alkalosis on water and electrolyte transport in the human colon.

Both the kidney and colon secrete bicarbonate and transport water and electrolytes. The respective contributions of these two organs to acid-base and electrolyte balance in normal man has thus been studied in eight healthy male volunteers who underwent simultaneous renal clearance studies, and colonic perfusion with a 0.9% saline or 7.2% mannitol solution, during metabolic alkalosis and acidosis, extracellular volume expansion, and control conditions. There was no influence of these acid-base conditions on electrolyte transport in the colon. In the urine, preferential loss of chloride over sodium averaged 81, 143 (P less than 0.001), and 141 (P less than 0.05) muequiv./min, during control, metabolic acidosis, and extracellular volume expansion conditions, respectively. During alkalosis more sodium than chloride was lost (146 muequiv./min) (P less than 0.001). Colonic pH averaged 7.41 during saline and 6.75 (P less than 0.005) during mannitol perfusion. Titratable acid was not produced in the colon during saline perfusion, and averaged 18 muequiv./min during mannitol perfusion. Urinary titratable acid increased from 19 to 25 muequiv./min (P less than 0.01) during volume expansion. With saline perfusion, bicarbonate secretion rate in the colon rose from 249 muequiv./min during control conditions to 289 muequiv./min during metabolic alkalosis (P less than 0.05). More bicarbonate was excreted in the urine during alkalosis when mannitol was introduced in the colon (243 muequiv./min) than when saline was perfused (152 muequiv./min) (P less than 0.05). This study indicates that the response of the human colon is trivial compared with that of the kidney during acute changes in acid-base balance.

Interrelationships of chloride, bicarbonate, sodium, and hydrogen transport in the human ileum.

Using a triple-lumen constant perfusion system, the following observations were made in normal subjects. First, chloride, bicarbonate, and sodium were found to exhibit net movement across ileal mucosa against electrochemical gradients. Second, during perfusion with a balanced electrolyte solution simulating plasma, the ileum generally absorbed, but sometimes secreted fluid. A reciprocal net movement of chloride and bicarbonate was noted when sodium movement was zero. Increasing rates of sodium absorption were associated with decreasing bicarbonate secretion rates and finally bicarbonate absorption. Even when bicarbonate was absorbed ileal contents were alkalinized (by contraction of luminal volume). Third, net chloride movement was found to be sensitive to bicarbonate concentration in ileal fluid. For instance, chloride was absorbed from solutions containing 14 or 44 mEq/liter of bicarbonate, but was secreted when ileal fluid contained 87 mEq/liter of bicarbonate. Fourth, when chloridefree (sulfate) solutions were infused, the ileum absorbed sodium bicarbonate and the ileal contents were acidified. Fifth, when plasma-like solutions were infused, the potential difference (PD) between skin and ileal lumen was near zero and did not change when chloride was replaced by sulfate in the perfusion solution. These results suggest that ileal electrolyte transport occurs via a simultaneous double exchange, Cl/HCO2 and Na/H. In this model neither the anion nor the cation exchange causes net ion movement; net movement results from the chemical reaction between hydrogen and bicarbonate. No other unitary model explains all of the following observations: (a) human ileal transport in vivo is essentially nonelectrogenic even though Na, Cl, and HCO3 are transported against electrochemical gradients, (b) the ileum can secrete as well as absorb, (c) ileal contents are alkalinized during absorption of or during secretion into a plasma-like solution, and (d) the ileum acidifies its contents when sulfate replaces chloride. Data obtained with a carbonic anhydrase inhibitor support the proposed model.

Transport of sodium and secretion of potassium and bicarbonate by the colon of normal and sodium‐depleted rats

1. Ascending and descending colonic segments of normal and Na-depleted rats were perfused in vivo with isotonic solutions of varying Na concentration and the unidirectional Na fluxes and secretion rate of K and bicarbonate and the transmucosal electrical p.d. were measured.2. Potential difference was greater in Na-depleted rats, especially towards the distal end of the descending colon. With reduction of luminal Na concentration, p.d. was reduced.3. The ascending and descending segments were similar in regard to Na transport except that the latter had lower passive permeability. Na depletion caused an increase of Na influx rate, Na net flux rate and Na exchange diffusion whilst the mucosal passive Na permeability decreased. These changes resulted in a reduction in the critical luminal Na concentration, i.e. the concentration at which the unidirectional fluxes were equal.4. K secretion rate was similar in the ascending and descending colon and was increased by Na depletion. In all rats, it was reduced when the luminal Na concentration was low.5. Bicarbonate secretion rate was unaffected by the Na depletion and all solutions remained isotonic during perfusion.6. The results confirmed that active Na transport was stimulated by Na depletion but indicated that this was probably not the only factor in the elevation of transmucosal p.d.