Net Sodium Flux Research Articles

Sodium absorption in the ferret Mustela putorius furo trachea

A net absorption of sodium was observed under control conditions in whole trachea. Luminal amiloride inhibited the net absorption of sodium. Luminal amiloride inhibited the transepithelial potential difference across the isolated trachea. Submucosal ouabain inhibited the net absorption of sodium. Submucosal ouabain inhibited the transepithelial potential difference across the isolated trachea. Short-circuited flat sheets of trachea manifested a net absorption of sodium. Serosal ouabain inhibited short-circuit current and net sodium flux across isolated flat sheets of trachea.

Intestinal transport of sodium, glucose and immunoglobulin in neonatal pigs. Effect of glucocorticoids.

The effect of cortisol on plasma immunoglobulin G (IgG) levels and on jejunal transport of sodium and glucose has been investigated in neonatal pigs (0-7 days of age). Five pigs were delivered vaginally (VD) at term (114-115 days gestation) and thirty-five by caesarean section (CS) 2-4 days before term (to circumvent a neonatal cortisol surge). Postnatally, twenty-seven CS pigs were injected with adrenocorticotrophic hormone (ACTH; n = 13), metyrapone (an inhibitor of adrenal 11 beta-hydroxylase activity, n = 7) or physiological saline (n = 7). Pigs were killed at birth, at 3 days, or at 6-7 days of age. Plasma concentrations of cortisol and IgG were determined and unidirectional fluxes of sodium and glucose measured across the proximal jejunum in vitro. Newborn CS pigs had significantly lower plasma cortisol but higher net fluxes of sodium and glucose than newborn VD pigs. At 3-7 days, metyrapone-treated pigs had significantly lower concentrations of cortisol and IgG in plasma and lower net fluxes of sodium and glucose than ACTH-treated pigs. Differences in net fluxes between treatment groups resulted from changes in both electrogenic and non-electrogenic sodium transport. Furthermore, sodium-glucose co-transport accounted for a major proportion of net sodium transport. High unidirectional fluxes in newborn CS pigs may be explained by the passage of large amounts of sodium through tight junctions and paracellular pathways in the prepartum period. The results indicate that cortisol stimulates net transport of sodium, glucose and immunoglobulins in the postnatal period of caesarean-delivered pigs. However, cortisol is unlikely to play a major regulatory role in the postnatal maturation of intestinal transport in normally delivered pigs.

Permeability of fetal microvessels in the perfused term human placenta

The toxicity of calcium ethylenediaminetetraacetate (CaEDTA) resulting from sustained iv infusion was studied in dogs. Signs of toxicity included vomiting, depression, and, occasionally, bloody diarrhea. The dogs were in a shocklike state terminally. Because of the reported nephrotoxicity of the drug, parameters of renal function were measured using conventional steady-state techniques. Glomerular filtration rate, renal plasma flow, and tubular maxima for glucose and PAH were decreased 8–22% following CaEDTA infusion; acetate enhancement of TmPAH was substantially reduced. Essentially no changes occurred in blood urea nitrogen, plasma electrolyte concentrations, or urinary excretion rates of sodium, potassium, or chloride. Histopathologic changes included hemorrhage and necrosis of intestinal epithelium with loss of villous structure and a necrotizing nephrosis of the proximal convoluted tubules.Evaluation of intestinal function revealed a marked depression of glucose absorption but no significant changes in the net fluxes of sodium, potassium, or chloride from the duodenum as toxicity developed. The permeability of the intestine to a volume marker was greatly increased. Studies of the intestinal diffusion ratios of solutes of various molecular sizes indicated the permeability increase was limited to the relatively large molecules.The results indicate CaEDTA is not primarily nephrotoxic in the dog and, therefore, renal failure probably is not the cause of death. The infusion of a very stable chelate, CrEDTA, was nontoxic. This suggested that CaEDTA toxicity is due to its chelative properties rather than some nonspecific action of the EDTA moiety.

Substrate-induced modulation of ATP turnover in dog and rabbit proximal tubules.

In dog proximal tubules in suspension, the addition of glucose increased significantly the ouabain-sensitive fraction of respiration, a response suppressed by phlorizin. The addition of alpha-methyl-D-glucoside (alpha-MG) had a modest effect and 3-O-methyl-D-glucoside (3-O-MG) had no effect. The different stimulation of the Na+,K(+)-ATPase activity elicited for each hexose could be explained by a different increment of net transepithelial flux of sodium induced by the sodium: hexose cotransport. This flux is a direct function of the transport characteristics of both luminal and antiluminal membranes of proximal cells for these sugars: glucose is rapidly transported by both membranes (allowing a large transepithelial flux of glucose: sodium) while alpha-MG is poorly transported by the basolateral, and 3-O-MG by the luminal, membrane of the dog proximal tubule (allowing a small transepithelial flux of hexoses and sodium). However the overall tubular respiration of dog proximal tubules was not increased by glucose addition because the increment in the ouabain-sensitive fraction was accompanied by a reciprocal decrement in an ouabain-insensitive but oligomycin- or N',N' dicyclohexylcarbodiimide (DCCD)-sensitive (or in the bafilomycin-sensitive) component of respiration. This component reflects the activity of a large BBM-bound H(+)-ATPase found in this species. The intracellular pH of dog proximal tubules in suspension was measured using the proton-sensitive fluorescent probe 2',7'-bis-2-(carboxyethyl)-5, (and 6)-carboxyfluorescein. Glucose application significantly alkalinized the cells. In contrast, other substrates such as lactate or acetate simultaneously acidified the cells and increased the ouabain-insensitive phosphorylative respiration of dog tubules. These observations suggest that a modulation of the activities of both the sodium and most probably the proton pump is elicited by substrate availability in suspensions of proximal tubules.

Evidence for a morphological component in acid-base regulation during environmental hypercapnia in the brown bullhead (Ictalurus nebulosus).

Exposure of adult brown bullheads Ictalurus nebulosus (120-450 g) to environmental hypercapnia (2% carbon dioxide in air) and subsequent recovery caused transient changes in whole body net sodium flux (JnetNa+) and net chloride flux (JnetCl-) resulting largely from changes in whole body sodium influx (JNa+in) and chloride influx (JinCl-). Scanning electron microscopy (SEM) revealed that the fractional area of chloride cells (CCs) on the interlamellar regions was reduced by 95% during environmental hypercapnia. During post-hypercapnic recovery, gill filament CC fractional area increased. The changes in JinCl- during and after environmental hypercapnia were closely associated with the changes in CC fractional area while the changes in JinNa+ did not correspond to the changes in CC fractional area. Transmission electron microscopy (TEM) supported the SEM observations of CC surface area changes and demonstrated that these changes were caused by covering/uncovering by adjacent pavement cells (PVCs). Lamellar and filament PVC microvilli density increased during hypercapnia while there was a subsequent reduction in the posthypercapnic period. These data suggest that an important mechanism of acid-base regulation during hypercapnic acidosis is modification of the chloride cell-associated Cl-/HCO3- exchange mechanism. We suggest that bullheads vary availability, and thus functional activity, of this transporter via reversible morphological alterations of the gill epithelium. The increase in density of PVC microvilli may be associated with sodium uptake and/or acidic equivalent excretion during acidosis.

Accumulation of potassium and calcium in rat myocardium exposed to alpha-1-adrenoceptor stimulation.

Net fluxes of potassium, calcium, sodium and chloride were examined in isolated perfused rat hearts during alpha-1-adrenoceptor stimulation. The ion measurements were performed in the non-recirculating perfusate. Hearts were exposed to alpha-1-adrenoceptor stimulation (phenylephrine 5 x 10(-5) mol/l in the presence of the beta-blocker timolol 10(-6) mol/l). During alpha-1-adrenoceptor stimulation perfusate potassium fell relatively rapidly by about 0.10 mmol/l after approximately 100 sec. followed by a slower rise. About 180 sec. after onset of alpha-1-adrenoceptor stimulation, the potassium level was about 0.06 mmol/l below the control concentration level. This reduction was eliminated by the alpha-1-adrenoceptor blocker prazosin (10(-7) mol/l). The effects on net calcium fluxes were measured at two different calcium concentrations. For both concentrations we found a small but statistically significant reduction of the calcium concentration in the perfusate after alpha-1-adrenoceptor stimulation. Neither sodium nor chloride perfusate concentrations showed statistical significant changes compared to control values. The present observations revealed the existence of alpha-1-adrenoceptor regulated mechanisms related to a net uptake of both potassium and calcium in rat heart.

Aldosterone regulation of active sodium chloride transport in the lizard colon (Gallotia galloti)

Bioelectrical parameters and unidirectional sodium and chloride fluxes were measured under voltageclamp conditions in groups of lizards submitted to single or chronic aldosterone treatment. Both acute (AT) and chronic (CT) treatment induced significant increases in the short-circuit current (Isc), as well as in the mucosa-to-serosa (Jm-sNa) and net sodium flux (JnetNa). In AT tissues, aldosterone did not change net chloride flux (JnetCl) but did so in CT tissues. Amiloride reduced the aldosterone-increased Isc in AT and CT tissues, inhibited JnetNain AT tissues and abolished it in CT colons. JnetClwas also reduced by the diuretic in the group of AT colons, whereas no changes were observed in the CT tissues. Addition of luminal DIDS reduced Na+ absorption and totally inhibited Cl- absorption in the AT tissues, but did not change Isc. However, in CT tissues neither Na+ nor Cl- transport were affected by DIDS. A good relationship between Isc and Jm-sNawas apparent after DIDS treatment in AT tissues. In this group, simultaneous addition of DIDS and amiloride totally abolished JnetNaand reduced Isc to untreated control values. Addition of serosal ouabain abolished Isc and Na+ absorption in AT and CT colons, but Cl- absorption was only altered in AT tissues. These results support the hypothesis that aldosterone induces an electrogenic, amiloride-sensitive sodium absorption, and in a dose-dependent fashion suppresses electroneutral NaCl absorption in the lizard colon.

Regulation of amiloride-sensitive Na + absorption in the lizard ( gallotia galloti) colon by aldosterone

1. 1. Acute (AT) or chronic (CT) administration of exogenous aldosterone brought about a considerable increase in transmural potential difference (PD), short-circuit current (Isc) and net sodium flux ( J net Na ). 2. 2. A good relationship between Isc and J m- s Na was observed in CT but not in AT or UC (untreated controls). 3. 3. Addition of mucosal amiloride reduced Isc in AT and CT colons, but did not cause any change in UC colons. The relationship between Isc and J m- s Na , observed in CT was totally suppressed by the diuretic. 4. 4. J net Na was reduced in AT tissues and abolished in CT colons by amiloride. 5. 5. The present results strongly suggest that aldosterone levels quantitatively and qualitatively modify sodium absorption across colonie mucosa in a dose-dependent fashion and that lower levels of the hormone are required to induce the electrogenic Na absorption than to suppress the electroneutral transport.

Haemodialysis: Effects on White and Red Blood Cell Sodium Content and Transport

A circulating sodium pump inhibitor, released in response to volume expansion, may, by increasing intracellular sodium concentrations, be responsible for some of the features of the uraemic state. Haemodialysis, by correcting volume overload, would be expected to be associated with a decrease in intracellular sodium towards normal. The effects of a haemodialysis session on leukocyte (WBC) sodium content and transport have not been described and there are conflicting reports of the effects of haemodialysis on erythrocyte (RBC) sodium content and transport. We have measured sodium (NaWBC/RBC) and potassium content (KWBC/RBC), net ouabain-sensitive sodium flux rate (FR) and sodium flux rate constant (RC) before and after a standard haemodialysis session in 20 stable hospital haemodialysis patients. In leukocytes (n = 18), sodium (P = 0.078), FR (P = 0.006), and RC (P = 0.071) decreased over dialysis, whereas in erythrocytes sodium increased (P less than 0.001, n = 19) and RC declined (P = 0.002, n = 18). Although in opposite directions in RBC and WBC, the changes in sodium were toward normal in both cell types. Changes in intracellular sodium content and transport did not correlate with changes in measures of ECF volume or biochemical efficiency of dialysis. We conclude that haemodialysis does affect cell sodium content and transport, but in different ways in different cell types. There was no evidence that haemodialysis removed a sodium pump inhibitor. The use of RBC or WBC as 'model' cells to study sodium transport in uraemia is of questionable validity.

Uncoupling of sodium chloride transport in premalignant mouse colon

Ion transport across premalignant large bowel mucosa in CF1 mice was evaluated by measuring sodium and chloride fluxes across voltage-clamped colonic segments obtained from control animals and animals treated for 4 wk with the procarcinogen 1,2-dimethylhydrazine, which induces tumor development principally in the distal colon. In control CF1 mouse colon, the net flux of sodium was 5.1 ± 0.7 and 4.6 ± 0.7 μEq · cm−2 · h−1 and the net flux of chloride was 6.1 ± 1.3 and 0.8 ± 1.2 μEq · cm−2 · h−1 in the distal and proximal colon, respectively. Removal of bicarbonate decreased the net flux of sodium 1.5 ± 0.5 and 1.9 ± 0.7 μEq · cm−2 · h−1 in the distal and proximal colon, respectively, while the net flux of chloride was decreased to 1.7 ± 1.8 μEq · cm−2 · h−1 in the distal colon but was unaltered (0.8 ± 0.1 μEq · cm−2 · h−1) in the proximal colon. Addition of 25 mM bicarbonate stimulated the net flux of sodium and chloride absorption in the distal colon but increased net flux of sodium absorption alone in the proximal colon and stimulated net flux of chloride secretion. Removal of chloride decreased net flux of sodium to 3.4 ± 1.4 and 1.8 ± 0.8 μEq · cm−2 · h−1 in the distal and proximal colon, respectively. Addition of 20 mM Cl stimulated net flux of sodium in the distal but not the proximal colon. These data suggest that sodium absorption is mediated by an electroneutral Cldependent, HCO3-dependent process (i.e., Na-H Cl-HCO3 dual exchange) in control distal colon and by an electroneutral HCO3-dependent process in control proximal colon. Following 1,2-dimethylhydrazine treatment, net flux of sodium in the distal colon was not stimulated by the addition of Cl or HCO3, and transport in the proximal colon was similar to that in control animals. However, 1,2-dimethylhydrazine treatment appears to uncouple Na-H C1-HCO3 exchange in the distal colon early in the process of large bowel carcinogenesis.

Effects of Glucose Transport Inhibitors on Corneal Swelling Rate and Endothelial Ion Fluxes

AbstractBased on the observation that several glucose transport inhibitors were found to reduce osmotically generated fluid flows across the rabbit corneal en-dothelium, these inhibitors have been examined for their influence on corneal swelling and ion fluxes across the endothelium. Using specular microscopy, phloretin (2 mM), cytochalasin B (20 µg/ml), and ethylidene-D-glucose (200 mM) were found to cause corneal swelling, whereas phlorid-zin (2 mM) and dihydrocytochalasin B (20 µg/ml) did not cause a swelling rate significantly different from controls. Each of the inhibitors caused changes in the unidirectional fluxes of sodium or bicarbonate, or both ions. None of the changes appeared to be related to the changes in corneal thickness. Cytochalasin B and dihydrocytochalasin B, for example, had no effect on net bicarbonate flux, yet both agents increased net sodium flux. Cytochalasin B, but not dihydrocytochalasin B, caused corneal swelling. Phloridzin decreased both net ion fluxes to zero, but had no e...

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

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

Effects of gastric fundic stimulation on glucose absorption and water and electrolyte fluxes from rabbit small bowel.

A single-pass perfusion model was developed to measure net fluxes of glucose, water, sodium, and potassium across upper jejunal and duodenal mucosa in vivo in the anaesthetised rabbit. Irrigation of the gastric fundic mucosa with Michaelis' buffer (pH 8) reduced jejunal mean glucose absorption by 21.3% (P less than 0.04) and duodenal glucose absorption by 27.2%. Irrigation of gastric fundic mucosa with 0.1 M glycine at pH 2 increased mean jejunal glucose absorption by 25%. Jejunal net secretion of water and sodium were reduced by gastric fundic alkali. Potassium net fluxes in jejunum and duodenum were not significantly affected. These results support the hypothesis that the gastric fundic mucosa is sensitive to chemical stimulation, responding by a humoral mechanism that modified the rate of glucose absorption from the small bowel mucosa.

Pulmonary glucose transport in the fetal sheep.

1. In the chronically catheterized sheep fetus between 122 and 143 days gestation the concentration of D-glucose in lung liquid was very low (usually less than 0.01 mM, the lower limit of detection of the analytical method) whereas the mean plasma concentration was 0.19 mM (S.E.M. 0.4, n = 13). 2. When the lung liquid concentration of D-glucose was raised to 1.67-5.00 mM, rapid uptake was observed until the concentration had fallen to its preceding low level. The uptake showed saturation kinetics (Vmax = 2.29-8.78 mumol/min, increasing with gestation; mean Km = 0.14 +/- 0.02 mM, n = 11, no change with gestation). This active uptake of glucose was blocked by phloridzin (10(-4) M). It was associated with a decrease in lung liquid secretion rate from which a change in net sodium flux could be inferred of an order suggesting one-to-one glucose-sodium co-transport. 3. Radiolabelled 3-O-methyl-D-glucose (3-O-meG) - a monosaccharide which is transported but not metabolized - was taken up rapidly from lung liquid and this rapid uptake was inhibited by D-glucose with 50% inhibition at 0.35 mM (+/- 0.08, n = 9). It was also inhibited by phloridzin (10(-4) M). 4. Radiolabelled 2-deoxy-D-glucose - a monosaccharide which is not a substrate for sodium-coupled transport - was taken up only very slowly from lung liquid; the rate of uptake was appropriate for passive diffusional transport and it was unaffected by the addition of D-glucose or phloridzin to lung liquid. 5. Intravenous infusion of D-glucose caused no detectable increase in the concentration of glucose in lung liquid unless phloridzin was added, when a slow increase was observed. 6. In two experiments with active transport blocked by phloridzin in lung liquid (10(-4) M), the rate of entry of labelled 3-O-meG from plasma to lung liquid was measured during intravenous infusion of this tracer for 29 and 23 h. The rates of entry were similar to the rate of efflux of the tracer from lung liquid when uptake was blocked by phloridzin or D-glucose, and similar to the rate expected for a metabolically inert tracer (i.e. it was some two orders of magnitude less than efflux from lung liquid in the absence of an inhibitor).(ABSTRACT TRUNCATED AT 400 WORDS)

Emergence of Na+-glucose cotransport in an epithelial secretory cell line sensitive to cholera toxin

Epithelial properties and effects of cholera toxin (CT) and glucose were investigated in human rectal tumor cell line HRT-18. Addition of 10(-3) M dibutyryl adenosine 3',5'-cyclic monophosphate (DbcAMP), 10(-8) M vasoactive intestinal peptide, 10(-5) M epinephrine, and 10(-5) M forskolin to the serosal side and of 3.5 micrograms/ml CT to the mucosal side and of 2 micrograms/ml A23187 to both the serosal and mucosal sides raised short-circuit current (Isc). This rise was reversed by serosal addition of 5 x 10(-5) M bumetanide or 10(-4) M ouabain. In filters treated with CT, Isc and net chloride flux (JClnet) increased after 60 min from 0.05 +/- 0.008 and -0.04 in the Ringer to 0.32 +/- 0.05 and -0.33 mueq.h-1.cm-2, respectively. Addition of 10(-2) M glucose further raised Isc by stimulating net sodium flux (JNanet) (0.70 +/- 0.08 and + 0.58 mueq.h-1.cm-2, respectively). This additional augmentation of Isc was reversed by 0.5 mM phlorizin and was mimicked by 3-O-methyl-D-glucose. When the filters were stimulated by cAMP for 15 min, Isc was also enhanced by addition of glucose. In untreated filters, Isc, JNanet, and JClnet did not differ significantly before and after addition of glucose. It is concluded that HRT-18 cells in basal state do not display absorptive properties but secretory properties stimulated by CT. However they exhibit Na+-glucose cotransport once stimulated by either CT or cAMP.

Electrophysiology of the Mantle of Anodonta Cygnea

ABSTRACT When gassed with a CO2-containing mixture, under short-circuit conditions, the isolated outer mantle epithelium (OME) of Anodonta cygnea generated a current which exhibited cyclic variations throughout the year. The intracellular potential, under short-circuit conditions, had an average value of –31 ±0·5 mV (N =65). The potential was sensitive to changes in concentration of potassium and chloride on the haemolymph side of the preparation, but not on the shell side, and was insensitive to changes in sodium concentration on either side. When the preparation was gassed with pure oxygen the current fell by 85 ± 1% (N = 8). A similar fall in current (88 ± 2%, N = 8) was observed when the solution bathing the apical side of the epithelium was prepared without bicarbonate and gassed with 95% O2 + 5% CO2. If this same bathing solution was gassed with 100% oxygen, the current fell by 67 ± 2% (N= 8) at pH7·2 and by 92±4% (N =8) at pH4·5. The short-circuit current was inhibited by DIDS (0·5 mmol 1−1) and SITS (0·5 mmol 1−1) when these drugs were applied on the haemolymph side. The current was also inhibited by DNP (1 mmol 1−1), iodoacetamide (1 mmol 1−1) and diamox (1 mmol 1−1). Amiloride (1 mmol 1−1) blocked the current but only when applied on the haemolymph side. Ouabain (0-1 mmol 1−1) did not affect the current. The net fluxes of rubidium (used as a tracer for potassium), chloride and calcium, measured with 86Rb, 36C1 and 45Ca, respectively, were very small when compared with the short-circuit current. There was a small net flux of sodium (measured with 22Na) towards the haemolymph side. The net flux of bicarbonate (measured with [14C]bicarbonate) was equal to the short-circuit current and was inhibited by DIDS. The permeability of the preparation to calcium was an order of magnitude higher than the permeability to sodium, potassium or chloride. The intracellular concentrations of potassium and chloride measured with ion-sensitive microelectrodes were 26·5 ±1·1 (N =16) and 7·9 ±0·3 (N =30) mmol 1−1, respectively. When these concentrations were measured with chemical methods the values found were 29·4 ±0·4 (N =20) and 12·9 ±0·6 (N =20) mmol 1−1, respectively. The chemically measured intracellular concentration of sodium was 14·0 ± 0·4 (N = 20) mmoll−1. When bicarbonate was removed from the haemolymph side the intracellular concentration of chloride increased. The movements of calcium across the OME are by simple diffusion and the calcification of the shell probably results from the balance between a diffusion of calcium towards the extrapallial compartment when a favourable electrochemical gradient for this ion is created and the equally passive movement of calcium which results from the uphill transport of bicarbonate ions carried out by the epithelium. The balance between these two processes might undergo annual cyclic variations.

Effects of acid-base variables on ion transport in rat colon.

Alterations in arterial acid-base variables have important effects on colonic electrolyte transport in vivo. To confirm the relative effects of these variables and to characterize the transport processes involved, we measured unidirectional 22Na and 36Cl fluxes across short-circuited, distal colonic mucosa of Sprague-Dawley rats. Stripped tissues were studied in Hepes buffer and in Ringer's solutions at HCO3 concentrations of 11, 21, and 39 mM, and CO2 tensions between 0 and 69.6 mmHg. Increases in PCO2, but not in either pH or HCO3 concentration, caused similar increases in JNanet and JClnet (net flux of sodium and chloride, respectively) from -0.2 +/- 0.3 and -1.5 +/- 0.4 mu eq/cm2 per h at PCO2 = 0 to 6.8 +/- 0.6 and 7.6 +/- 0.7 mu eq/cm2 per h, respectively, at PCO2 = 69.6 mmHg. These increases were accounted for by changes in Jms and were accompanied by small decreases in Isc. 1 mM acetazolamide decreased both JNanet and JClnet and their responses to increases in CO2. 0.75 mM luminal amiloride prevented the increase in sodium absorption, but did not affect the CO2-induced increase in chloride absorption. In the presence of amiloride, CO2 increased JR (residual flux). 0.1 mM luminal furosemide did not affect the CO2-induced increases in JNanet in the absence or presence of amiloride. Changes in HCO3 concentration did not alter JR. We conclude that ambient CO2 effects active, electroneutral sodium absorption in the rat distal colon. The process stimulated by CO2 is dependent on mucosal carbonic anhydrase activity and most likely represents Na/H and Cl/HCO3 ion exchange.

Effects of atropine and tetrodotoxin on neurotensin-induced ileal sodium transport in the dog.

1. Neurotensin was infused intravenously, in the presence or absence of intravenous atropine or intraarterial tetrodotoxin, into dogs anaesthetized with sodium pentobarbitone. Net and unidirectional fluxes of sodium and blood flows in the ileum were measured. Arterial and mesenteric venous blood pressures, haematocrits and plasma total solids were also determined. 2. Neurotensin caused a transient increase in net sodium absorption which was not associated with significant changes in unidirectional fluxes. This was followed by prolonged net secretion which was associated with an increase in unidirectional sodium secretion and a smaller decrease in sodium absorption. Potassium secretion was also increased when net sodium secretion increased. 3. Neurotensin increased haematocrit and total solids and decreased arterial pressure at the same time that secretion occurred. 4. Atropine blocked all the cardiovascular effects of neurotensin and reduced its early effects on both absorption and secretion but not the later effects on secretion. Tetrodotoxin only blocked the increase in absorption but not the secretion or the cardiovascular effects. 5. It was concluded that there is a cholinergic step in the cardiovascular effects of neurotensin and that the early effects of neurotensin on secretion are due to active secretion supported by fluid leakage from the plasma. The later effects of neurotensin on secretion do not have a cholinergic step and are due primarily to an active secretion. The increased absorption is mediated partly through intrinsic nerves of the gut.

Gamma-Aminobutyric acid transport in reconstituted preparations from rat brain: coupled sodium and chloride fluxes.

Transport of gamma-aminobutyric acid (GABA) is electrogenic and completely depends on the presence of both sodium and chloride ions. These ions appear to be cotransported with gamma-aminobutyric acid through its transporter [reviewed in Kanner, B. I. (1983) Biochim. Biophys. Acta 726, 293-316]. Using proteoliposomes into which a partially purified gamma-aminobutyric acid transporter preparation was reconstituted, we have been able--for the first time--to provide direct evidence for sodium- and chloride-coupled gamma-aminobutyric acid transport. This has been done by measuring the fluxes of 22Na+, 36Cl-, and [3H]GABA. These fluxes have the following characteristics: There are components of the net fluxes of sodium and chloride that are gamma-aminobutyric acid dependent. The sodium flux is chloride dependent; i.e., when Cl- is replaced by inorganic phosphate or by SO4(2-), gamma-aminobutyric acid dependent sodium fluxes are abolished. The chloride flux is sodium dependent; i.e., when Na+ is replaced by Tris+ or by Li+, gamma-aminobutyric acid dependent chloride fluxes are abolished. Thus, the gamma-aminobutyric acid dependent sodium and chloride fluxes appear to be catalyzed by the transporter. Using these fluxes we have attempted to determine the stoichiometry of the process. We measured the initial rate of sodium-dependent gamma-aminobutyric acid fluxes and that of gamma-aminobutyric acid dependent sodium fluxes. This yields the stoichiometry between sodium and gamma-aminobutyric acid (2.58 +/- 0.99). Similarly, we measured the stoichiometry between chloride and gamma-aminobutyric acid, which is found to be 1.27 +/- 0.12.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of lipase in the pathogenesis of experimental esophagitis in the rabbit.

The role of lipase in the pathogenesis of reflux esophagitis was investigated in an experimental model in which an in situ isolated segment of rabbit esophagus was perfused (at pH 7) with a solution containing lipase in concentrations of 2 and 10 mg/ml. The severity of mucosal damage was assessed using the following indicators of mucosal integrity: transmucosal potential difference, net flux of sodium, and mucosal permeability to erythritol labeled with carbon 14, a neutral molecule with a greatest molecular diameter of 8.2 nm. Furthermore, the morphologic characteristics of esophageal damage were studied by light and scanning electron microscopy. The results suggest that lipase significantly decreased transmucosal potential difference and increased mucosal permeability to sodium and erythritol labeled with carbon 14. Morphologically, lipase induced cytoplasmatic vesiculation and widening of intercellular spaces within the basal cell layer. The epithelial cell layers were also often seen to be sloughed off with consequent exposure of the subepithelial connective tissue at the mucosal surface. The findings suggest that lipase has an adverse effect on the esophageal mucosa that may have pathogenetic significance in clinical reflux esophagitis.