Luminal Sodium Concentration Research Articles

Comparative cation dependency of sugar transport by crustacean hepatopancreas and intestine.

ABSTRACTGlucose is transported in crustacean hepatopancreas and intestine by Na+-dependent co-transport, while Na+-dependent D-fructose influx has only been described for the hepatopancreas. It is still unclear if the two sugars are independently transported by two distinct cation-dependent co-transporter carrier systems. In this study, lobster (Homarus americanus) hepatopancreas brush border membrane vesicles (BBMV) were used to characterize, in detail, the cation-dependency of both D-[3H]-glucose and D-[3H]-fructose influxes, while in vitro perfused intestines were employed to determine the nature of cation-dependent sugar transport across this organ. Over the sodium concentration range of 0–100 mM, both [3H]-glucose and [3H]-fructose influxes (0.1 mM; 1 min uptakes) by hepatopancreatic BBMV were hyperbolic functions of [Na+]. [3H]-glucose and [3H]-fructose influxes by hepatopancreatic BBMV over a potassium concentration range of 15–100 mM were hyperbolic functions of [K+]. Both sugars displayed significant (p<0.01) Na+/K+-dependent and cation-independent uptake processes. Transepithelial 25 µM [3H]-glucose and [3H]-fructose fluxes across lobster intestine over luminal sodium and potassium concentration ranges of 0–50 mM and 5–100 mM, respectively, were hyperbolic functions of luminal [Na+] and [K+]. As with hepatopancreatic sugar transport, transepithelial intestinal sugar transport exhibited both significant (p<0.01) Na+/K+-dependent and cation-independent processes. Results suggest that both D-glucose and D-fructose are transported by a single SGLT-type carrier in each organ with sodium being the “preferred”, high affinity, cation for both sugars in the hepatopancreas, and potassium being the “preferred”, high affinity, cation for both sugars in the intestine.

Comparative sugar transport by crustacean hepatopancreas and intestine

Glucose is transported in crustacean hepatopancreas and intestine by Na+‐dependent cotransport, while Na+‐dependent D‐fructose influx has only been described for the hepatopancreas. In this study lobster (Homarus americanus) hepatopancreas brush border membrane vesicles (BBMV) were used to characterize the cation‐dependency of both 3H‐D‐glucose and 3H‐D‐fructose influxes, while in vitro perfused intestines were employed to determine the nature of cation‐dependent sugar transport in this organ. Over the sodium concentration range of 0–100 mM, both 3H‐D‐glucose and 3H‐D‐fructose influxes (0.1 mM; 1 min uptakes) by hepatopancreatic BBMV were hyperbolic functions of [Na+], exhibiting Km values of 2.30 +/− 0.59 mM (glucose) and 3.79 +/− 1.02 mM (fructose). 3H‐D‐fructose influx by hepatopancreatic BBMV over a potassium concentration range of 15–100 mM was a hyperbolic function of [K+], exhibiting Km value of 12.5 +/− 0.6 mM. Transepithelial 25 μM 3H‐D‐glucose and 3H‐D‐fructose fluxes across lobster intestine over a luminal sodium concentration range of 1 – 50 mM were hyperbolic functions of luminal [Na+], displaying Km values of 6.05 +/− 0.99 mM (glucose) and 10.58 +/− 1.65 mM (fructose). Results suggest that there may be a single carrier process in both organs with a higher affinity for NaCl than for KCl and displays a substrate specificity considerably different than that demonstrated by mammalian SGLT1.

Hypertonic saline inhibits luminal sodium channels in respiratory epithelium

Physical exercise with increased ventilation leads to a considerable rise in water loss from the airways. The mechanisms underlying the regulation of transepithelial fluid transport necessary to compensate for these losses are unknown but may include changes in luminal ion channel conductance. The present study was designed to examine the effects of an increase in luminal chloride and sodium concentrations which may locally occur during hyperventilation on luminal ion conductance in the respiratory epithelium of healthy controls and patients diagnosed with cystic fibrosis (CF). Changes in luminal chloride and sodium conductance were inferred by recording nasal potential difference in eight healthy subjects and 10 patients with CF, using superfusing solutions based on isotonic saline (150 mM) on one occasion and solutions based on hypertonic saline (300 mM) on the other. Switching from isotonic to hypertonic saline superfusion decreased potential difference in controls and CF patients significantly. Amiloride induced a decrease of potential difference which was larger with isotonic than with hypertonic saline (controls 9.5 +/- 6.1 vs. 3.7 +/- 4.6 mV; CF 17.2 +/- 7.2 vs. 9.8 +/- 7.6 mV). Chloride conductance stimulated with solutions low in chloride and containing isoproterenol was not significantly changed by hypertonic saline solutions compared with isotonic solutions in both groups. The findings indicate a significant inhibition of luminal sodium conductance by high luminal sodium concentrations. This mechanism may be involved in the regulation of fluid transport across the respiratory epithelium during exercise and in the improvement of mucociliary clearance and lung functions with inhalation of hypertonic saline in CF.

Endogenous prolactin modulated the calcium absorption in the jejunum of suckling rats

Prolactin has been reported to stimulate intestinal calcium absorption in young and mature, but not aging rats. The present study was performed on suckling rats to elucidate the actions of endogenous prolactin on calcium absorption in various intestinal segments. Before measuring the calcium fluxes, 9-day-old rats were administered for 7 days with 0.9% NaCl, s.c. (control), 3 mg/kg bromocriptine, i.p., twice daily to abolish secretion of endogenous prolactin, or bromocriptine plus exogenous 2.5 mg/kg prolactin, s.c. Thereafter, the 16-day-old rats were experimented upon by instilling the 45Ca-containing solution into the intestinal segments. The results showed that, under a physiological condition, the jejunum had the highest rate of calcium absorption compared with other segments (1.4 +/- 0.35 micromol.h-1.cm-1, p < 0.05). The duodenum and ileum also manifested calcium absorption, whereas the colon showed calcium secretion. Lack of endogenous prolactin decreased lumen-to-plasma and net calcium fluxes in jejunum from 2.07 +/- 0.31 to 1.19 +/- 0.12 and 1.40 +/- 0.35 to 0.88 +/- 0.18 micromol.h-1.cm-1 (p < 0.05), respectively, and exogenous prolactin restored the jejunal calcium absorption to the control value. Endogenous prolactin also had an effect on the duodenum but, in this case, exogenous prolactin did not reverse the effect of bromocriptine. However, neither ileal nor colonic calcium fluxes were influenced by prolactin. Because luminal sodium concentration has been demonstrated to affect calcium absorption in mature rats, the effect of varying luminal sodium concentrations on calcium fluxes in suckling rats was evaluated. The jejunum was used due to its highest rate of calcium absorption. After filling the jejunal segments with 124 (control), 80, 40 mmol/L Na+-containing or Na+-free solution, increases in calcium absorption were found to be inversely related to luminal sodium concentrations in both control and bromocriptine-treated rats. The plasma concentration of 45Ca under luminal sodium free condition was also higher than that of the control condition (2.26% +/- 0.07% vs. 2.01% +/- 0.09% administered dose, p < 0.05). However, 3H-mannitol, a marker of the widening of tight junction that was introduced into the lumen, had a stable level in the plasma during an increase in plasma 45Ca, suggesting that the widening of tight junction was not required for enhanced calcium absorption. In conclusion, calcium absorption in suckling rats was of the highest rate in the jejunum where endogenous prolactin modulated calcium absorption without increasing the paracellular transport of mannitol.

Maturation of Rabbit Proximal Straight Tubule NaCl Transport † 1833

The present in vitro microperfusion study compared the mechanism and rates of NaCl transport in neonatal and adult rabbit proximal straight tubules. In proximal straight tubules perfused with a late proximal tubular fluid and bathed in a serum-like albumin solution, the rate of volume absorption(Jv) was 0.54±0.10 and 0.12±0.05 nl/mm·min in adults and neonates, respectively (p<0.05). With the addition of 10-5M bath ouabain, Jv decreased to 0.27±0.07 and-0.03±0.04 nl/mm·min in adult and neonatal tubules, respectively(p<0.05), consistent with lower rates of active and passive NaCl transport in the neonatal proximal straight tubule. The rate of change of intracellular pH (pHi) in response to a change in luminal sodium and chloride concentration was used to assess the relative rates of Na+/H+ and Cl-/base exchange, respectively. The rates of Na+/H+ antiporter activity was 37.7±4.9 and 206.1±25.2 pmol/mm·min (p<0.01) in neonatal and adult proximal straight tubules, respectively. Cl-/base exchange was 6.0±1.2 and 45.7±6.6 pmol/mm·min (p<0.01) in neonatal and adult proximal straight tubules, respectively. In both neonatal and adult proximal straight tubules the rate of Cl-/base exchange was not affected by formate, bicarbonate, or cyanide and acetazolamide, but was inhibited by DIDS, consistent with Cl-/OH- exchange. These data demonstrate an increase in both active and passive proximal straight tubule NaCl transport during postnatal renal development. The increase in active NaCl transport is due to increases in both Na+/H+ antiporter and Cl-/OH- exchange activity.

Acute effects of prolactin on passive calcium absorption in the small intestine by in vivo perfusion technique

The acute effect of intraperitoneally administered prolactin (0.2, 0.4, and 0.6 mg/kg body weight) on passive calcium transport in duodenum, proximal jejunum, and ileum of sexually mature female Wistar rats was investigated by using an in vivo perfusion technique. Test solution containing (in mM) NaCl, 100; KCl, 4.7; MgSO4, 1.2; CaCl2, 20; D-glucose, 11; sodium ferrocyanide (Na4Fe(CN)6), an index of net water transport, 20; and 0.7 microCi 45CaCl2 (1 Ci = 37 GBq) was perfused through the 10-cm intestinal loop for 60 min. Results showed that 0.4 mg prolactin/kg body weight significantly increased duodenal net Ca absorption (net Ca) from 23.81 +/- 1.84 to 30.56 +/- 1.57 mmol/g dry weight (p < 0.05) by stimulating the lumen to plasma calcium flux (CaL-P). The jejunum responded to 0.2, 0.4, and 0.6 mg prolactin/kg body weight by reversing from net Ca absorption of 18.60 +/- 1.70 mmol/g dry weight to net secretion of -3.30 +/- 1.56, -10.39 +/- 2.21, and -11.79 +/- 2.04 mmol/g dry weight (p < 0.01), respectively, as a result of a dose-dependent increase in plasma to lumen calcium flux (CaP-L). Calcium fluxes in the ileum on the other hand did not respond to prolactin. There was a close correlation between net water flux and net calcium flux in all three intestinal segments under basal condition regardless of the luminal sodium concentration. However, this correlation was lost after prolactin administration, which while having no effect on net water flux, altered the duodenal and jejunal calcium fluxes. By varying the luminal concentration of sodium, it was found that the stimulatory effect of 0.4 mg prolactin/kg body weight on the duodenal CaL-P was reduced when compared with control, i.e., 17.84 +/- 0.91 vs. 26.64 +/- 1.05 mmol/g dry weight at a sodium concentration of 180 mM, and 14.48 +/- 0.99 vs. 20.12 +/- 1.34 mmol/g dry weight at a sodium concentration of 140 mM. At a sodium concentration of 80 mM, the prolactin effect was absent. Since duodenal Na(+)-K+ ATPase activity was increased by prolactin from 3.77 +/- 0.16 to 4.95 +/- 0.30 mumol Pi.mg-1 protein.h-1 (p < 0.05), sodium dependency of the prolactin-enhanced lumen to plasma calcium flux may be related to both sodium-induced water flow and calcium-sodium exchange across the basolateral membrane. Thus, it was postulated that under basal condition, net calcium transport in the small intestine occurred with the sodium-induced water transport along the paracellular pathway. However, after prolactin administration, this association was lost. Prolactin-enhanced lumen to plasma calcium flux in the duodenum was sodium dependent and involved the Na(+)-K+ ATPase activity. In the proximal jejunum, prolactin stimulated plasma to lumen calcium flux, but the mechanism was not known.

Acute effects of prolactin on passive calcium absorption in the small intestine by in vivo perfusion technique

The acute effect of intraperitoneally administered prolactin (0.2, 0.4, and 0.6 mg/kg body weight) on passive calcium transport in duodenum, proximal jejunum, and ileum of sexually mature female Wistar rats was investigated by using an in vivo perfusion technique. Test solution containing (in mM) NaCl, 100; KCl, 4.7; MgSO4, 1.2; CaCl2, 20; D-glucose, 11; sodium ferrocyanide (Na4Fe(CN)6), an index of net water transport, 20; and 0.7 microCi 45CaCl2 (1 Ci = 37 GBq) was perfused through the 10-cm intestinal loop for 60 min. Results showed that 0.4 mg prolactin/kg body weight significantly increased duodenal net Ca absorption (net Ca) from 23.81 +/- 1.84 to 30.56 +/- 1.57 mmol/g dry weight (p < 0.05) by stimulating the lumen to plasma calcium flux (CaL-P). The jejunum responded to 0.2, 0.4, and 0.6 mg prolactin/kg body weight by reversing from net Ca absorption of 18.60 +/- 1.70 mmol/g dry weight to net secretion of -3.30 +/- 1.56, -10.39 +/- 2.21, and -11.79 +/- 2.04 mmol/g dry weight (p < 0.01), respectively, as a result of a dose-dependent increase in plasma to lumen calcium flux (CaP-L). Calcium fluxes in the ileum on the other hand did not respond to prolactin. There was a close correlation between net water flux and net calcium flux in all three intestinal segments under basal condition regardless of the luminal sodium concentration. However, this correlation was lost after prolactin administration, which while having no effect on net water flux, altered the duodenal and jejunal calcium fluxes. By varying the luminal concentration of sodium, it was found that the stimulatory effect of 0.4 mg prolactin/kg body weight on the duodenal CaL-P was reduced when compared with control, i.e., 17.84 +/- 0.91 vs. 26.64 +/- 1.05 mmol/g dry weight at a sodium concentration of 180 mM, and 14.48 +/- 0.99 vs. 20.12 +/- 1.34 mmol/g dry weight at a sodium concentration of 140 mM. At a sodium concentration of 80 mM, the prolactin effect was absent. Since duodenal Na(+)-K+ ATPase activity was increased by prolactin from 3.77 +/- 0.16 to 4.95 +/- 0.30 mumol Pi.mg-1 protein.h-1 (p < 0.05), sodium dependency of the prolactin-enhanced lumen to plasma calcium flux may be related to both sodium-induced water flow and calcium-sodium exchange across the basolateral membrane. Thus, it was postulated that under basal condition, net calcium transport in the small intestine occurred with the sodium-induced water transport along the paracellular pathway. However, after prolactin administration, this association was lost. Prolactin-enhanced lumen to plasma calcium flux in the duodenum was sodium dependent and involved the Na(+)-K+ ATPase activity. In the proximal jejunum, prolactin stimulated plasma to lumen calcium flux, but the mechanism was not known.

Maturation of renal potassium transport

The studies outlined in this review suggest that the immaturity of distal nephron segments may hinder urinary excretion of potassium early in life. Among the factors that may limit potassium secretion by principal cells in the neonatal cortical collecting duct are an unfavorable electrochemical gradient (reduced Ki, Na(+)-K(+)-ATPase activity and/or Vte), limited membrane permeability to potassium and sodium, low tubular fluid flow rate, reduced luminal sodium concentration, or increased paracellular backleak. Alternatively, enhanced potassium absorption by other relatively well-differentiated distal nephron segments may contribute in part to a reduced net potassium excretory rate in the newborn. It should be kept in mind, however, that the limited potassium secretory capacity of the immature kidney becomes clinically relevant only under conditions of potassium excess. Under normal circumstances, the tendency of the newborn to retain potassium is an appropriate and necessary condition for growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation of the amiloride-blockable sodium channel from epithelial tissue

The first step in net active transepithelial transport of sodium in tight epithelia is mediated by the amiloride-blockable sodium channel in the apical membrane. This sodium channel is the primary site for discretionary control of total body sodium and, therefore, investigating its regulatory mechanisms is important to our understanding of the physiology of fluid and electrolyte balance. Because essentially all of the regulatory sites on the channel are on the intracellular surface, patch clamp methods have proven extremely useful in the electrophysiological characterization of the sodium channel by isolating it from other channel proteins in the epithelial membrane and by allowing access to the intracellular surface of the protein. We have examined three different regulatory mechanisms. (1) Inhibition of channel activity by activation of protein kinase C; (2) activation of the channel by agents which activate G-proteins; and (3) modulation of channel kinetics and channel number by mineralocorticoids. Activation of protein kinase C by phorbol esters or synthetic diacylglycerols reduces the open probability of sodium channels. Protein kinase C can be activated in a physiological context by enhancing apical sodium entry. Actions which reduce sodium entry (low luminal sodium concentrations or the apical application of amiloride) increase channel open probability. The link between sodium entry and activation of protein kinase C appears to be mediated by intracellular calcium activity linked to sodium via a sodium/calcium exchange system. Thus, the intracellular sodium concentration is coupled to sodium entry in a negative feedback loop which promotes constant total entry of sodium. Activation of G-proteins by pertussis toxin greatly increases the open probability of sodium channels. Since channels can also be activated by pertussis toxin or GTP gamma S in excised patches, the G-protein appears to be closely linked in the apical membrane to the sodium channel protein itself. The mechanism for activation of this apical G-protein, when most hormonal and transmitter receptors are physically located on the basolateral membrane, is unclear. Mineralocorticoids such as aldosterone have at least two distinct effects. First, as expected, increasing levels of aldosterone increase the density of functional channels detectable in the apical membrane. Second, contrary to expectations, application of aldosterone increases the open probability of sodium channels. Thus aldosterone promotes the functional appearance of new sodium channels and promotes increased sodium entry through both new and pre-existant channels.

Effect of vasopressin analogue (dDAVP) on potassium transport in medullary collecting duct.

The microcatheterization technique was used to examine electrolyte transport in the medullary collecting duct of two groups of anesthetized rats during water diuresis and during a second experimental phase with 1-desamino-8-D-arginine vasopressin (dDAVP) administration or continued water diuresis. Potassium reabsorption of 53-61% of the delivered load was consistently observed in the medullary collecting duct during water diuresis. During dDAVP administration, urinary potassium excretion doubled, and there was no net potassium transport (reabsorption or secretion) in the medullary collecting duct. The change in potassium transport in medullary collecting duct from water diuresis to antidiuresis (dDAVP) was sufficient to account for the increase in urinary potassium excretion. Changes in flow rate, luminal sodium concentration, or collecting duct sodium reabsorption could not account for the changes in potassium transport in the collecting duct during dDAVP. The results are interpreted as indicating that dDAVP stimulates potassium entry (secretion) into the medullary collecting duct, probably by a direct effect. This action of antidiuretic hormone appears to be important in maintaining potassium homeostasis during changing water balance.

Cortical collecting tubule potassium secretion: Effect of amiloride, ouabain, and luminal sodium concentration

The present study examined the effect of sodium transport inhibition by amiloride, ouabain, and luminal sodium removal on potassium secretion in isolated cortical collecting tubules from adrenalectomized and DOCA-stimulated rabbits. Collecting tubules from adrenalectomized rabbits had a mean potassium secretion of 3.62 +/- 0.37 pmoles X mm-1 X min-1, which significantly decreased to 1.52 +/- 0.21 pmoles X mm-1 X min-1 after addition of amiloride, but no additional effect was observed after the addition of ouabain. The transepithelial voltage (VT) became less positive after exposure to amiloride. Cortical collecting tubules from DOCA-treated animals exhibited significantly greater potassium secretion (28.6 +/- 9.4 pmoles X mm-1 X mm-1). Amiloride totally inhibited potassium secretion, and VT reversed polarity in these tubules. In tubules from adrenalectomized rabbits the removal of luminal sodium inhibited potassium secretion by approximately 44% but had no effect on VT. There remained, however, a substantial amount of potassium secretion in the absence of transepithelial sodium flux. Thus, potassium secretion in the cortical collecting tubule is highly dependent on sodium reabsorption under conditions of mineralocorticoid stimulation but significantly less so in adrenalectomized animals. Potassium secretion in the cortical collecting tubule of adrenalectomized rabbits is inhibited independent of VT and occurs, in part, by an apparent electroneutral process. Chronic exposure to mineralocorticoids appears to stimulate electrogenic sodium reabsorption and potassium secretion.

Mutual dependence of sodium and chloride absorption by renal distal tubule.

Sodium transport and chloride transport by the renal distal tubule of rats were studied by in vivo continuous microperfusion to determine the effects of separately altering luminal sodium and chloride concentrations. Results showed that sodium absorption depends on luminal sodium concentration and chloride absorption depends on luminal chloride concentration; both relations are linear between approximately 10 and 100 mM and have slopes of approximately 2.5 pmol X min-1 X mM-1. Sodium absorption is also a saturable function of luminal chloride concentration, and chloride absorption is a saturable function of luminal sodium concentration; the half-maximal chloride and sodium concentrations are approximately 10 mM. Furosemide, 10(-4) M, when added to the fluid used to perfuse this segment inhibited sodium absorption and chloride absorption to a similar extent. Removal of chloride from luminal fluid (replaced with sulfate) and addition of furosemide to the perfusion fluid had little or no effect on the measured transepithelial voltage. The results are consistent with the presence of a mechanism in the luminal membrane of distal tubule cells that couples the absorptive transport of sodium and chloride.

Distribution of sodium in cellular and luminal compartments of turtle thyroid glands.

Sodium distribution in luminal and cellular compartments of turtle thyroid was studied by measurements of radiosodium uptakes into whole thyroid and luminal fluid, sampled with micropipettes, and of Na+ activities in the luminal and cellular fluids of thyroid follicles with a liquid ion-exchange microelectrode. Thyroid water and electrolyte contents were also determined chemically. Radiosodium uptake by both the whole thyroid and by the luminal fluid of control and thyrotropin (TSH)-treated turtles did not reach maximal levels until 16-24h after injection of the radioisotope. In control animals, the volumes of distribution of radiosodium in the whole thyroid and the luminal fluid were much smaller than those calculated from the chemical analysis data for the corresponding tissues. TSH increased the radiosodium spaces to values almost equal to those of the chemically determined sodium spaces. Luminal fluid sodium concentration increased after TSH and decreased after ouabain and furosemide treatments. Intracellular sodium concentration markedly increased after ouabain and decreased after TSH and furosemide. These and our previous results suggest a Na+-I- cotransport mechanism in the thyroid.

Relationship between peritubular membrane potential and net fluid reabsorption in the distal renal tubule of Amphiuma.

Amphiuma kidneys were isolated and perfused with modified Ringer solution and peritubular and transepithelial membrane potentials (p.d.s) in distal tubules measured with micro-electrodes during rapid changes of luminal electrolyte concentrations. Peritubular membrane potential and net fluid reabsorption (split-oil-droplet method) were also measured with and without application of various drugs known to alter transport. Raising the luminal sodium concentration from 10 to 100 mM reversibly increased the peritubular p.d. The magnitude of the peritubular p.d. was a saturable function of luminal sodium concentration. In the presence of chloride in the lumen the peritubular hyperpolarization following increased luminal sodium could be inhibited by luminal amiloride (10(-4)M). Sodium-induced hyperpolarization of the peritubular p.d. could be completely inhibited by 10(-5)M-ouabain. Adding amiloride (10(-4)M) to the luminal fluid rapidly and reversibly depolarized the peritubular p.d. and inhibited fluid reabsorption. Addition of amphotericin B (20 micrograms/ml) to the luminal perfusion solution had no effect on peritubular p.d. at 100 mM-luminal NaCl but at 10 mM-NaCl, peritubular p.d. hyperpolarized. Fluid reabsorption was stimulated (with 100 mM-NaCl in the lumen). Addition of amphotericin when the tubule was perfused on both sides with solutions containing a constant potassium concentration of 78 mM and a variable sodium concentration ranging from 7.8 to 34.5 mM revealed strong dependence of the peritubular hyperpolarization on the sodium concentration. Luminal furosemide (10(-4)M) and chlorothiazide (10(-4)M) and peritubular ethacrynic acid (10(-4)M) all reduced fluid reabsorption but hyperpolarized the peritubular p.d. The data suggest the presence of an electrogenic sodium transport process in the peritubular membrane that directly contributes to the generation of the peritubular potential. In addition, chloride transport has an important role in determining this potential.

Aging: its influence on the intestinal unstirred water layer thickness, surface area, and resistance in the unanesthetized rat.

The intestinal absorption of some nutrients changes with aging. As the unstirred water layer (UWL) is an important rate limiting step in the absorption of nutrients in general and of lipid soluble nutrients in particular, we investigated possible changes in the UWL dimensions in the aging rat in vivo. We measured the thickness (d) of the UWL using rapid changes in the luminal sodium concentration to induce changes in the transmucosal potential differences. We assessed the surface area (Sw) and resistance (d/SwD) of the UWL at varying flow rates by using increasingly lipophilic medium chain saturated alcohols as probes. At high UWL resistance, d decreased from 318 to 268 microns between 1 and 29 months of age. As the animals aged, Sw changed from 114 to 106 cm2/100 cm and from 262 to 214 cm2/100 cm at low and high flow rates, respectively, using dodecanol as a probe. The resistance of the UWL (d/SwD) remained relatively stable at all ages studied. These experiments demonstrate that age-related changes in absorption are dependent on the aqueous diffusion coefficient and degree of lipid solubility of the specific nutrients. At low UWL resistance, absorption of compounds with higher diffusion coefficients and greater aqueous solubility is decreased with aging. In contrast, previous studies have demonstrated that the absorption of nutrients with low diffusion coefficients and high lipid solubility increases with aging especially when the resistance of the UWL is high.

Relation between intracellular sodium and active sodium transport in rabbit colon: current-voltage relations of the apical sodium entry mechanism in the presence of varying luminal sodium concentrations.

The current-voltage relations of the amiloride-sensitive Na entry pathway across the apical membrane of rabbit descending colon, exposed to a high K serosal solution, were determined in the presence of varying mucosal Na activities, (Na)m, ranging from 6.2 to 99.4 mM. These relations could be closely fit to the "constant field" flux equation yielding estimates of the permeability of the apical membrane to Na, PmNa, and the intracellular Na activity, (Na)c. The following empirical relations emerged: (Na)c increased hyperbolically with increasing (Na)m; PmNa decreased hyperbolically with increasing (Na)m and linearly with increasing (Na)c; spontaneous variations in Na entry rate at constant (Na)m could be attributed entirely to parallel, spontaneous variations in PmNa; the rate of Na entry increased hyperbolically with increasing (Na)m obeying simple Michaelis-Menten kinetics; the relation between (Na)c and "pump rate," however, was sharply sigmoidal and could be fit by the Hill equation assuming strong cooperative interactions between Na and multiple sites on the pump; the Hill coefficient was 2-3 and the value of (Na)c at which the pump-rate is half-maximal was 24 mM. The results provide an internally consistent set of relations among Na entry across the apical membrane, the intracellular Na activity and basolateral pump rate that is also consistent with data previously reported for this and other Na-absorbing epithelia.

Potassium secretion by cortical collecting tubule: relation to sodium absorption, luminal sodium concentration, and transepithelial voltage.

Sodium absorption and K secretion were measured in isolated perfused rabbit cortical collecting tubules. To increase the range of transport rates some tubules were dissected from rabbit pretreated with DOcA. K secretin was unaffected by varying axial volume flow from 4 to 15 nl/min. K secretion was, however, correlated with transepithelial voltage and Na absorption. The Na:K transfer ratio was 1.35. In tubules dissected from normal rabbits, K secretion was almost eliminated by reducing Na concentration in the lumen to near 0 and was unaffected by varying luminal Na concentration from 30 to 145 mM. These data, together with other experimental results reported by several investigators, are consistent with a model for K secretion that places the rate-limiting step at the Na-K pump located on the basolateral membrane. The apical (luminal) membrane appears to be highly permeable to K.

Relationship between sodium and bicarbonate transport in the rat proximal convoluted tubule.

The relationship between net sodium and bicarbonate transport was studied by microperfusion of proximal convoluted tubules and peritubular capillaries. Bicarbonate absorption was unchanged as long as the sodium concentration remained above 40 meq/liter, despite reduction of sodium transport to 10% of its control value. At a sodium concentration of 5 meq/liter, fluid absorption was completely abolished but bicarbonate transport was reduced to 39% of its control value. Even at reduction of luminal and peritubular sodium concentrations to nominally zero, bicarbonate transport continued at 23% of its control value. Amiloride, at a sodium concentration of 5 meq/liter, inhibited bicarbonate absorption in a dose-dependent manner. Elevating peritubular pH to 8.4 drastically reduced net bicarbonate transport, whereas fluid absorption was only slightly inhibited. These results are consistent with a dual mechanism of acidification: a sodium-hydrogen exchange that saturates at low extracellular sodium concentrations and an additional sodium-independent mechanism of hydrogen ion secretion.

Importance of sodium and glucose for the establishment of a villous tissue hyperosmolality by the intestinal countercurrent multiplier.

The intestinal countercurrent multiplier has earlier been shown to create an increased tissue osmolality in the villi (Jodal et al. 1978). In the present paper the importance of varying the luminal contents on the creation of the villous hyperosmolality was investigated using the cryoscopic technique described by Jodal et al. (1978). The perfusion solutions used contained 0, 25 or 147 mmol Na/l and were either provided with mannitol or glucose (30 mmol/l). It was demonstrated that sodium was of particular importance for the establishment of the villous hyperosmolality while glucose only contributed significantly at low luminal sodium concentrations. It is therefore proposed that glucose only in the absence of sodium in the luminal perfusate may effectively participate in the generation of the villous tissue hyperosmolality via the countercurrent multiplication mechanism.

Luminal influences on potassium secretion: sodium concentration and fluid flow rate

Two methods of in vivo continuous microperfusion were used to evaluate separately luminal sodium concentration and fluid flow rate as factors regulating potassium secretion by the renal distal tubule of the rat. Emphasis was placed on evaluating changes in sodium concentration (43-97 mM) and flow rate (4-27 nl/min) within the physiological range. Absolute rates of Na, K, Cl, and H2O transport were measured. Results showed that increasing early distal flow rate without increasing early distal Na concentration significantly increased the absolute rate of potassium secretion by the distal tubule. In contrast, increasing early distal Na concentration, distal Na delivery, and distal Na absorption did not affect potassium secretion if flow rate was not changed. Further studies showed that reducing early distal Na concentration below the physiological range (to 15 mM) caused the direction of net sodium transport to be reversed but did not significantly reduce potassium secretion. Increasing early distal K concentration (to 34 mM) caused the direction of net potassium transport to be reversed. The rate of potassium secretion appears to depend in part on the luminal potassium concentration. Increases in luminal flow rate may increase the rate of potassium secretion by lowering the luminal K concentration.