Transmucosal Electrical Potential Difference Research Articles

NaPi-mediated Transcellular Permeation is the Dominant Route in Intestinal Inorganic Phosphate Absorption in Rats

Inorganic phosphate in food is absorbed two ways, the transcellular route via the brush border membrane and the paracellular route via tight junctions. NaPi, a sodium-dependent inorganic phosphate transporter, is expressed in rat and human intestine. However, the relative contribution of NaPi to total carrier-mediated transport of physiological concentrations of inorganic phosphate in rat intestine is not clear. Here, we characterized inorganic phosphate transport across the rat small intestine using a voltage-clamp analysis which allowed the diffrentiation of inorganic phosphate permeation through these two (transcellular and paracellular) routes. Results showed that, under a physiologically normal transmucosal electrical potential difference (about 2 mV), permeation of inorganic phosphate by the transcellular route was greater than that by the paracellular route. Further, transport was significantly decreased by the addition to the incubation medium of phosphonoformic acid, a sodium-dependent phosphate transporter inhibitor, and severely inhibited under sodium-free conditions. Similar results were obtained without the voltage-clamp. Together, these results suggest that NaPi-mediated transcellular permeation is the dominant route in the absorption of inorganic phosphate across the small intestine.

A New Method for Drug Transport Studies on Pig Nasal Mucosa Using a Horizontal Ussing Chamber

The horizontal Ussing chamber method described here allows performance of transport studies on pig nasal respiratory mucosa under conditions simulating reality in that it mimics the air–mucosa interface. The transport of testosterone and mannitol through pig nasal mucosa in the horizontal Ussing chamber was investigated using both liquid and air mucosal interfaces. There were no significant differences in either the bioelectrical parameters (transmucosal electrical resistance, R, potential difference, PD, and short circuit current, Isc) or the apparent permeability (Papp) of the mucosa to testosterone or mannitol between the liquid and air interface experiments. The histological study showed that the epithelial cell layer tolerates exposure to the air interface well. The Papp equation was developed to correct for substance binding to the wall of the receiver chamber. The mean values±SD of R, PD, and Isc for the mucosae in the study were 75.0±28.0 Ωcm2, (−4.53)±3.46 mV and 58.6±28.8 μA/cm2, respectively. The corrected Papp for testosterone with and without the mucosal air interface were 9.82·10−6±11.41·10−6 cm/s and 32.24·10−6±31.12·10−6 cm/s, respectively. The Papp values for mannitol with and without the air interface were 2.26·10−6±1.42·10−6 cm/s and 3.12·10−6±1.72·10−6 cm/s, respectively. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:1259–1273, 2002

Acetazolamide inhibits basal and stimulated HCO 3− secretion in the human proximal duodenum

Background/Aims : Carbonic anhydrase activity plays a role in electrolyte transport in many tissues. This study examined the effect of the carbonic anhydrase inhibitor acetazolamide on human basal and prostaglandin E 2- and acid-stimulated duodenal mucosal bicarbonate secretion and transmucosal electrical potential difference. Methods : Seven healthy volunteers participated in four separate experiments. The variables included oral acetazolamide vs. control test and, as agonists of bicarbonate secretion, either luminal acidification or luminal prostaglandin E 2. The proximal 4 cm of the duodenum (i.e., the duodenal bulb) was isolated between balloons as previously described and perfused with an HCO 3 −-containing (24 mmol/L) balanced electrolyte glucose-containing (10 mmol/L) solution. Results : Acetazolamide treatment significantly decreased mean basal HCO 3 − secretion and basal transmucosal potential difference. After luminal acidification, duodenal mucosal bicarbonate increased significantly after both acetazolamide treatment (mean, 626; 95% CI, 91–1160 μmol·cm −1·h −1) and in the control tests (mean, 868; 95% CI, 652–1084 μmol·cm −1·h −1). However, acetazolamide treatment significantly decreased prostaglandin E 2-stimulated HCO 3 − secretion from 461 (95% CI, 307–615) to 222 (95% CI, 121–324) μmol·cm −1·h −1. Conclusions : Duodenal mucosal carbonic anhydrase activity has an important function in the regulation of basal and prostaglandin E 2-stimulated human duodenal mucosal bicarbonate transport.

Transmucosal Potential Difference as an Index of Esophageal Mucosal Integrity

All the epithelia lining the gastrointestinal (GI) tract, including that of the esophagus, exhibit a transmucosal electrical potential difference (PD). The luminal surface of the GI mucosa is indeed electrically negative when compared with the serosal one. Although it was initially felt that the body of the esophagus exhibits a PD near 0 or slightly positive, recent studies, using parenteral reference electrodes, have shown a negative PD of around -15 mV. Measurement of esophageal PD has been mainly used to locate both the lower and the upper esophageal sphincters but very rarely to evaluate esophageal mucosal integrity in clinical settings, most probably due to the difficulties encountered during measurement of mucosal PD. Reliable techniques to measure esophageal PD simultaneously with esophageal pressure or mucosal pH are now available. Application of these recently developed methodologies showed that measurement of esophageal PD during either manometry or endoscopy provides meaningful information about mucosal integrity. Indeed, tissue injury, either neoplastic of inflammatory, usually results in a less negative PD. In contrast, an abnormally high negative PD is very often observed in patients with columnar-lined lower esophagus. In patients with microscopic reflux esophagitis, PD exhibits less negative values which are significantly correlated with the degree of the mucosal damage. Normalization of the altered PD after either medical or surgical treatment makes it an additional parameter to evaluate the effect of a given therapy.

Stimulation of mucosal alkaline secretion in rat duodenum by dopamine and dopaminergic compounds

Background: The catechol-O-methyl-transferase (COMT) inhibitor nitecapone, which prevents mucosal degradation of dopamine, and some dopamine receptor agonists ameliorate gastroduodenal mucosal damage. Therefore, their effects on mucosal bicarbonate secretion were studied. Methods: Duodenum just distal to the Brunner's glands area was cannulated in situ in anesthetized rats. Bicarbonate secretion into the luminal perfusate and transmucosal electrical potential difference (PD) were recorded. Results: Intravenous dopamine (50 μg · kg−1 · h−1) increased bicarbonate secretion twofold, and a higher rate of infusion (250 μg · kg−1 · h−1) resulted in a further increase. Neither dose affected the PD. The dopamine D1 agonist SKF-38393 (10–50 μg/kg) and the COMT inhibitor nitecapone (50–500 μg/kg) caused dose-dependent increases in secretion, similar to that observed with dopamine. Domperidone, a peripherally acting dopamine antagonist, inhibited the stimulatory effects of SKF-38393 and nitecapone. Hexamethonium or the α-adrenoceptor antagonist phentolamine, in contrast, did not affect the response to nitecapone. Intracerebroventricular administration of nitecapone was without effect. Conclusions: A probable electroneutral component of duodenal mucosal bicarbonate secretion is stimulated via peripheral dopamine D1 receptors. This may contribute to the previously observed ulceroprotective actions of dopaminergic compounds.

Oesophageal and gastric potential difference and pH in healthy volunteers following intake of coca-cola, red wine, and alcohol.

Alcohol causes gastroesophageal reflux and mucosal damage in the oesophagus and the stomach. The transmucosal electrical potential difference gives information on gastric mucosal integrity and function, while the validity of oesophageal measurements have been discussed. Baseline oesophageal potential difference measurements were performed three times with an interval of at least one week. We found oesophageal potential difference measurements reliable with an acceptable reproducibility. Oesophageal and gastric potential difference and pH were measured by use of a new microelectrode principle in 10 healthy volunteers following intake of coca-cola, wine and alcohol. Oesophageal and gastric potential difference decreased after intake of 250 ml coca-cola, 250 ml 11 vol% red wine and 60 ml 43 vol% whisky. Gastric potential difference decreased after intake of 250 ml ethanol 11 vol% and 60 ml ethanol 43 vol%. Intake of red wine and whisky resulted in a significant greater gastric potential difference decrease compared to similar concentrations and volumes of ethanol. The time until the potential difference had regained baseline level was longer after intake of red wine compared to coca-cola, whisky and ethanol. Oesophageal pH decreased after intake of coca-cola and red wine, but was unchanged after whisky. Gastric pH was unchanged after intake of all the drinks. In conclusion, the gastric potential difference reduction was not correlated to alcohol concentration. Red wine seems to affect the gastric potential difference more than coca-cola, whisky and ethanol. The observed changes in oesophageal and gastric potential difference might be due to changes in Cl- secretion and/or due to a damaging effect of the additives of the beverages.

Paracellular and Transcellular Permeabilities of Fosfomycin across Small Intestinal Membrane of Rat and Rabbit by Voltage-Clamp Method.

The permeability of fosfomycin (FOM), which is a low molecular weight and water-soluble antibiotic, across rat and rabbit jejunal membrane was investigated on a paracellular route and a transcellular route separated by voltage-clamp method. It was determined that FOM permeates through these two routes in both animals. Under a physiologically normal condition, the transmucosal electrical potential difference (about 2 mV), the contribution of the transcellular route to FOM membrane permeability was greater than that of the paracellular route. The transcellular permeability was significantly reduced in the presence of inorganic phosphate. The inhibitory effects of the inorganic phosphate coincided with our reports on FOM uptake by rat jejunal brush-border membrane vesicles in vitro and on FOM absorption by rat jejunal single-pass perfusion in situ.

Electrical Potential Difference Across the Stomach Wall and Gastric Morphology in Anaesthetized Pigs After Intravenous Administration of Cytotoxic Drugs

Nausea and vomiting are frequent side-effects of cancer chemotherapy. To investigate whether such therapy has an acute toxic effect on the gastric mucosa, cyclophosphamide, epirubicin and fluorouracil were administered intravenously to anaesthetized pigs. Gastric mucosal function was evaluated by continuous measurements of the gastric transmucosal electrical potential difference (PD) and the intragastric pH by using a newly developed microelectrode principle. After sacrifice, gastric histology was examined. During chemotherapy a significant decline in gastric PD was observed two hours after drug infusion, indicating a hampered gastric mucosal function. Apart from a slight hyperemia, gastric histology was normal. In this animal model a change in gastric mucosal function developed at the same time after chemotherapy as the gastric side-effects in humans.

Influence of atrial natriuretic peptide on mammalian large intestine

Atrial natriuretic peptide is distributed in a number of organs including the large intestine. Atrial natriuretic peptide has potent diuretic and natriuretic properties and appears to play a central role in fluid and electrolyte homeostasis by an action on the kidney. We examined the influence of atrial natriuretic peptide on mammalian colon because this organ is also intimately involved in homeostasis. Segments of the distal colons of male Sprague-Dawley rats were stripped of muscle layers and mounted in flux chambers. Atrial natriuretic peptide, when added to the serosal side of the mucosa, in concentrations ranging from 10−8–10−5 M, caused a rapid, concentration-dependent increase in short-circuit current, transmucosal electrical potential difference, and conductance. The response to atrial natriuretic peptide was inhibited by (a) chloride-free solution on the serosal surface; (b) pretreatment of the tissues with the chloride channel blocker, diphenylamine-2-carboxylate (10−3 M mucosally); (c) pretreatment with d,l-verapamil (10−4 M mucosally and serosally); (d) calcium-free solution on the serosal surface; (e) pretreatment with tetrodotoxin (10−7 M to serosal surface); and (f) pretreatment with atropine (10−5 M serosally). However, the response to atrial natriuretic peptide was not influenced by pretreatment with amiloride (10−4 M to mucosal and serosal surfaces) or piroxicam (10−5 M serosally). Atrial natriuretic peptide did not elicit an increase in shortcircuit current and potential difference across T84 cells derived from a human colonic carcinoma cell line, suggesting that the response to atrial natriuretic peptide is not due to a direct effect on colonocytes. These findings suggest that atrial natriuretic peptide acts by a calcium-mediated secretory mechanism involving cholinergic nerves and is likely to be involved in the endogenous neurohumoral regulation of ion transport in the mammalian colon.

Stimulation of duodenal mucosal bicarbonate secretion in the rat by brain peptides

Bicarbonate secretion by duodenal mucosa free of Brunner's glands was titrated in situ in anesthetized rats. Intracerebroventricular infusion of thyrotropin-releasing hormone (0.01–1 μg/h), bombesin, gastrin-releasing peptide, or corticotropin-releasing factor increased the bicarbonate secretion and the transmucosal electrical potential difference. The increase in secretion in response to thyrotropin-releasing hormone and bombesin was prevented by cervical vagotomy. Intravenous administration of the α-adrenoceptor antagonist phentolamine increased the magnitude and duration of the response, suggesting that these two peptides in addition to eliciting vagal stimulation of the duodenal secretion, by sympathetic activation, inhibit the secretion. Intravenous thyrotropin-releasing hormone (3.6 mg/kg) did not affect the secretion, further indicating that effects were elicited within the central nervous system. Intracerebroventricular infusion of cholecystokinin-octapeptide or β-endorphin had no effect on duodenal bicarbonate secretion or on the potential difference. The latter peptide was a potent stimulant of the secretion when injected intravenously and probably acts at a peripheral site. The central nervous control of duodenal mucosal bicarbonate secretion is thus influenced by some specific peptides that are known to occur in brain tissue, and duodenal protection against acid might be modulated by agents affecting this control.

Pathogenesis of water-immersion stress-induced gastric ulcers in rats with renal failure.

Rats with or without renal failure, produced by uranyl acetate, were subjected to water-immersion stress for 6 h. The severity of stress-induced gastric ulcers in the renal failure group was significantly higher than that in the control group. The intragastric pH did not significantly differ between the two groups. Transmucosal electrical potential difference, gastric mucosal blood flow, and gastric mucosal hexosamine content in the renal failure group were significantly lower than in the control group. These results suggest that decreases in defensive factors, rather than an increase in an aggressive factor, may be more closely involved in the development of acute gastric ulcers in rats with renal failure.

Epithelial restitution in the gastrointestinal tract.

Injury to the gastrointestinal mucosa can be divided into two types: (a) deep injury involving extensive hemorrhage and large areas of tissue necrosis, and (b) superficial injury confined to the upper regions of the mucosa and not involving hemorrhagic lesions. Mucosal repair differs according to the severity of the damage. Repair of deep injury takes weeks because large regions of the mucosa must be replaced with new tissue, a process involving mitosis. Superficial injury is initially repaired rapidly over hours by epithelial restitution that does not involve mitosis but proceeds in the following sequence of events: First, the damaged surface epithelial cells are shed and form a layer that protects the restituting mucosa. Then the viable epithelial cells that remain attached to the mucosa at the margin of the wound become flattened and rapidly migrate over the denuded basal lamina. The superficial epithelium is re-established when migrating cells touch, form new tight junctions, and repolarize their organelles. This rapid protective mechanism, called restitution, has recently been documented in the stomach, duodenum, colon, and rectum. The cellular mechanisms, speed of migration, recovery of transmucosal electrical potential difference, and specific peculiarities of rapid epithelial restitution in the various regions of the gastrointestinal tract are reviewed here.

Stimulation of mucosal bicarbonate secretion in rat duodenum in vivo by BW755C.

Bicarbonate secretion from 12 mm segments of duodenum just distal to the Brunner's gland area was titrated (pH 7.60) in situ in anesthetized rats. Intravenous BW755C (10-20 mg/kg) increased both bicarbonate secretion and the transmucosal electrical potential difference and pretreatment with indomethacin (3 mg/kg intravenously) prevented these effects. Indomethacin also inhibited stimulation of HCO3- secretion by luminal acid (10 mM HCl) but had no effect on the rise in secretion in response to exogenous (luminal) prostaglandin E2. The results support previous suggestions of a role for endogenous prostaglandins in mediation of the HCO3- response to acid and are consistent with the recent demonstration that BW755C increased prostaglandin formation in homogenates of rat intestinal mucosa. Stimulation of HCO3- secretion by BW755C was not enhanced but attenuated by preexposure to luminal acid, suggesting that the latter increases secretion by effects other than mucosal mobilization of arachidonate.

Influence of obstructive jaundice on gastric mucosal barrier in dogs.

The influence of obstructive jaundice on the gastric mucosal barrier was studied before and after ligation of the common bile duct using 21 mongrel dogs with a Heidenhain pouch. The gastric mucosal barrier was examined using gastric mucosal permeability of ionic net fluxes of Na+ and H+ (delta Na+, delta H+), and transmucosal electrical potential difference (PD) during the irrigation of the pouch with various test solutions. No significant differences in delta Na+ or delta H+ during the irrigation with 100 mN HCl were found between before and after obstructive jaundice. Almost the same results were observed during the irrigation with 150 mN HCl. Obvious increases in delta Na+ and delta H+ were found, when 20 mM sodium taurocholate (taurocholate) was used in addition to 100 mN HCl. No differences were, however, found between before and after obstructive jaundice. The PD during the irrigation with 100 and 150 mN HCl showed about the same levels of -50 mV. The PD decreased early during the irrigation with 20 mM taurocholate in addition to 100 mN HCl, but no differences were found in these values between before and after obstructive jaundice. Dose-response relationships were found between the concentration of taurocholate in addition to 100 mN HCl, and delta Na+, delta H+ and sigma PD/15 min, while no differences in ED50 of taurocholate for delta Na+, delta H+ or sigma PD/15 min were observed between before and after obstructive jaundice. These results suggest that obstructive jaundice itself exerts no influence on the gastric mucosal barrier with respect to gastric mucosal permeability and PD in dogs.

Gastric and duodenal HCO3- transport in vivo: influence of prostaglandins.

Gastric and duodenal HCO3- transport was compared in the same mammalian species (cat) in vivo. The most appropriate technique for detecting HCO3- in the lumen of the stomach was measurement of pH and CO2 tension, whereas in the duodenum it was pH-stat titration. For experiments on gastric HCO3- transport, conscious cats prepared with vagally denervated fundic pouches were used; for those on duodenal transport anesthetized animals with in situ perfused segments were studied. When expressed in terms of gross surface area, basal HCO3- output was six times greater in the duodenum than in the stomach (approximately 1.5 cf. approximately 0.25 mumol X cm-2 X 15 min-1). topical application of 16,16-dimethyl prostaglandin E2 (dmPGE2) to duodenal mucosa caused a concentration-dependent increase in HCO3- output and transmucosal electrical potential difference (PD) over the range 0.01-1.0 microgram X ml-1. PGE2 was approximately 200 times less potent than dmPGE2 as a stimulant of duodenal HCO3- transport. Increases in the rate of luminal HCO3- output following application of dmPGE2 were considerably less in the stomach compared with the duodenum (approximately 50% cf. approximately 1,000% at 1 microgram X ml-1). Intravenous dmPGE2 (1 microgram X kg-1 X h-1) had no effect on either gastric or duodenal HCO3- outputs. Indomethacin (5 mg X kg-1 iv) inhibited duodenal HCO3- output by approximately 50% and reduced PD but did not influence gastric HCO3- output. We propose that in the cat duodenum in vivo local prostaglandins regulate HCO3- transport, but in the cat stomach in vivo they have a less important role.

The effect of secretin on canine gastric mucosal HCO 3− production

Recent studies suggest that HCO 3 − production by surface epithelium may protect gastric mucosa against H + back diffusion. Agents shown to increase gastric HCO 3 − include prostaglandins, carbachol, dibutyryl c-GMP, ethanol, Ca 2+, and cimetidine. This study was initiated to evaluate the effect of secretin on gastric mucosal HCO 3 − production. Six dogs with Heidenhain pouches were fasted 24 hr. Each study consisted of nine 15-min periods: three control periods of iv saline infusion; three test periods which followed an iv bolus of 0.15 clin units/kg secretin; and three test periods which followed an iv bolus of 0.30 clin units/kg secretin. The intragastric test solution consisted of 100 m M NaCl, 20 m M mannitol, and 50 m M EPPS buffer; pH was adjusted to 8.0–8.2 using 19 M NaOH. Fifty milliliters test solution was instilled in the pouch and a zero-time sample was taken; after 15 min a final sample was taken, the pouch was rinsed, and the next period begun. HCO 3 −, Na +, K +, and Cl − concentrations were measured as well as transmucosal electrical potential difference (PD) changes and changes in volume, pH, and osmolality. [ 14C]PEG was utilized to measure residual volume. In the first 15-min period following each secretin bolus, significant ( P < 0.05) increases in intraluminal gastric HCO 3 − occurred. However, doubling the secretin dose did not significantly increase the measured HCO 3 − when compared to the lower dose. Also undetectable were changes in ionic fluxes accompanying the increases in intraluminal HCO 3 − which might have suggested a mechanism of the HCO 3 − production. In addition to its previously described properties of acid inhibition and gastric mucus stimulation, this study demonstrates that secretin also induces production of gastric HCO 3 −. The clinical significance of these modest increases remains to be determined but they may contribute to gastric mucosal barrier defense.

AN EXPERIMENTAL STUDY ON ESOPHAGEAL TRANSMUCOSAL POTENTIAL DIFFERENCE AND ITS DIAGNOSTIC VALUE IN ESOPHAGITIS

Since Donné reported on the existence of transmucosal electrical potential difference in 1834, many investigations have been made on this subject. Recently, the fact that the potential difference reflects mucosal integrity has been utilized to examine the extent of mucosal pathology of various parts of the alimentary tract. Few reports, however, have so far been made on the esophageal mucosal potential difference. The author experimentally studied on the esophageal mucosal potential difference to seek its significance in making the diagnosis of esophagitis. A total of 25 mongrel dogs were used and divided into two groups, control and esophagitis group. Endoscopic examination, recording of potential difference and autopsy were made after preparation of esophagitis. The results obtained were as follows: 1) Esophagoscopy of the esophagitis group revealed various types of esophagitis in all the dogs. 2) Gastric mucosal potential difference varied according to the degree of mucosal damage. 3) In esophagitis group, esophageal mucosal potential difference showed the higher values than those of the control group. 4) At the area of localized esophagitis, the value of esophageal mucosal potential difference was higher than that of the intact mucosa. It is concluded that the measurement of potential difference of the esophageal mucosa is useful for detecting the extent of esophageal mucosal damage.

Stimulation of duodenal epithelial HCO 3− transport in the guinea pig and cat by luminal prostaglandin E 2

Segments of guinea pig or cat duodenum distal to the Brunner gland containing area and devoid of bile or pancreatic secretions were cannulated in situ. The unbuffered luminal solution was gassed with 100% O 2 or N 2 and HCO 3 − transport titrated at pH 7.40 or 8.00 with solutions containing HCl. Cat duodenum transported HCO 3 − at a greater rate (∼17μeq, cm −1, h −1) than did jejunum in the same animals (∼5μeq, cm −1, h −1) and also developed a greater transmucosal electrical potential difference. Luminal application of PGE 2 (1 – 12 μM) in cat duodenum increased HCO 3 − transport and the potential difference. HCO 3 − transport by guinea pig duodenum (∼27 μeq, cm −1, h −1) was increased by luminal PGE 2 only in animals where transport had been inhibited by pretreatment with aspirin (30 mg/kg intravenously). Exposure of the cat duodenal lumen to HCl (1 – 25 mM, 5 min) stimulated HCO 3 − transport and continuous exposure of duodenum in the guinea pig to acid discharged from the stomach may increase endogenous prostaglandin concentrations, resulting in an apparent lack of effect of exogenous prostaglandins. The present results and previous similar findings in amphibians in vitro suggest that surface epithelial transport of HCO 3 − protects duodenal mucosa against acid.

The effect of cathartic agents on transmucosal electrical potential difference in the human rectum

Active ion transport in the colon is generating a transmucosal electrical potential difference (PD) of about 40 mV. Cathartic agents inhibit electrolyte and water net-absorption or cause net-secretion which should be reflected in a change of PD. In 83 normal subjects the effect of an isotonic eletrolyte solution (control) and different cathartic agents on rectal PD was tested: Laxatives (bisacodyl, rhein), bile acids (cholic and deoxycholic acid), fatty acids (oleic and ricinoleic acid) and cardiac glycosides (meproscillarin, digitoxin, digoxin). Bisacodyl, deoxycholic acid in high concentration, meproscillarin and digitoxin significantly decreased PD, while the other substances did not. Cathartics act on different transport mechanisms which together with different absorption characteristics of the proximal and distal colon may explain the difference in effecting the PD. Rectal PD measurement provides an easy and convenient tool to document effects of cathartic agents on electrolyte transport, otherwise difficult to obtain, and is applicable for clinical use.

Applied pressures and net water flux across in vitro frog gastric mucosa.

The effects of hydrostatic pressure differences up to 0.4 atm/413 cmH2O were studied on frog gastric mucosa in vitro. Net water flux, transmucosal electrical potential difference, and acid secretion were measured. A significant correlation between hydrostatistic pressure difference and net water flow (r=0.77) was obtained. The intercept of the regression line, at zero hydrostatic pressure difference, is 9.3 +/- 0.5 microliter/cm2.h, and the slope 42.9 +/- 3.2 microliter/cm2.atm.h. No significant correlation was obtained between the hydrostatic pressure difference and the transmucosal potential difference (P greater than 0.20), the acid secretion (P greater than 0.20), or the nonacidic chloride transport, measured as short-circuit current (P greater than 0.20). Hydrostatic water flux is compared to osmotically induced flux previously reported. It is proposed that the difference between hydrostatic and osmotic induced water fluxes is due to the area of cells exposed to the pressures. Only part of surface cells are directly exposed to the osmotic pressure due to the presence of restricted extracellular compartments.