Low-dose glucocorticoids maintain Na-H exchange in distal colon of adrenalectomized rats

1991 ◽  
Vol 261 (3) ◽  
pp. F545-F553 ◽  
Author(s):  
C. P. Bastl ◽  
L. Bressler ◽  
G. Schulman ◽  
M. Mendez ◽  
E. J. Cragoe
Keyword(s):  
Short Circuit ◽  
In Vitro Study ◽  
Short Circuit Current ◽  
Distal Colon ◽  
Ion Flux ◽  
Rat Colon ◽  
Anion Secretion ◽  
Stimulation Of

With in vivo perfusion we demonstrated that physiological doses of glucocorticoids restore Na and Cl absorption in adrenalectomized rat colon. The absorption is spironolactone and amiloride resistant and is inhibited by the Na-H inhibitor, 5-(N-ethyl-N-isopropyl)amiloride (EIPA), suggesting that glucocorticoids modulate Na-H antiport. The present in vitro study examines pathways mediated by glucocorticoids in adrenalectomized rat distal colon and rectum. In vivo administration of 2.5 micrograms/100 g body wt dexamethasone did not alter serosal-to-mucosal flux or tissue electrical parameters but restored mucosal-to-serosal flux and net Na and Cl absorption within 2–3 h of administration to levels found in intact rat colon. Transport was not inhibited by 10(-5) M amiloride but was eliminated by 10(-5) M EIPA. After 26 h of dexamethasone, an amiloride-resistant short-circuit current was stimulated, accompanied by increased residual ion flux in rectum, but not distal colon, suggesting that a delayed or secondary effect of glucocorticoids is stimulation of electrogenic anion secretion. Thus adrenalectomy reduces net ion flux in distal colon by its effect on electroneutral mucosal-to-serosal NaCl flux. Small doses of glucocorticoids completely ameliorate this effect via stimulation of the Na-H antiport. Glucocorticoids maintain basal electroneutral NaCl absorption in distal rat colon.

Suppression of coupled Na-Cl absorption by aldosterone and dexamethasone in rat distal colon in vitro

1984 ◽  
Vol 246 (6) ◽  
pp. F785-F793 ◽  
Author(s):  
R. D. Perrone ◽  
S. L. Jenks
Keyword(s):  
Short Circuit ◽  
Short Circuit Current ◽  
Distal Colon ◽  
Rat Colon ◽  
Na Transport ◽  
Unidirectional Flux ◽  
Rat Distal Colon ◽  
Marked Suppression ◽  
Stimulation Of

Basal Na absorption in the rat colon is coupled to that of Cl in an electroneutral fashion. We previously determined that aldosterone or dexamethasone induces amiloride-sensitive mucosal-to-serosal Na flux approximately equal to the amiloride-sensitive short-circuit current in rat distal colon in vitro. However, the effect of these steroids on coupled Na-Cl absorption was not examined. For this purpose, we determined the unidirectional flux of Na and Cl in voltage-clamped distal colon segments from rats treated with aldosterone or dexamethasone. Amiloride was used as a probe for conductive Na absorption, and acetazolamide and Cl-free solutions were used as probes for coupled Na-Cl absorption. Our results indicate that the nature of colonic Na absorption is markedly changed after treatment with these steroids. In contrast to findings in the untreated rat, colonic Na absorption after treatment with aldosterone or dexamethasone was largely independent of the presence of Cl. Net Cl absorption and acetazolamide sensitivity were both greatly diminished. Thus, aldosterone and dexamethasone have multiple effects on Na transport in rat distal colon. In addition to the stimulation of conductive Na absorption by aldosterone, an effect well described in other epithelia, there is marked suppression of coupled Na-Cl absorption. Dexamethasone was less effective in suppressing Cl absorption but equally effective in stimulating conductive Na absorption. These steroid effects were greater in the terminal 1-2 cm of the rat colon.

Chronic regulation of transepithelial Na+ transport by the rate of apical Na+ entry

1996 ◽  
Vol 270 (2) ◽  
pp. C600-C607 ◽  
Author(s):  
M. D. Rokaw ◽  
E. Sarac ◽  
E. Lechman ◽  
M. West ◽  
J. Angeski ◽  
...  
Keyword(s):  
Short Circuit ◽  
Basolateral Membrane ◽  
Short Circuit Current ◽  
Maximal Activity ◽  
Na Channels ◽  
Na Transport ◽  
Bottom Structures ◽  
Stimulation Of

In several settings in vivo, prolonged inhibition of apical Na+ entry reduces and prolonged stimulation of apical entry enhances the ability of renal epithelial cells to reabsorb Na+, an important feature of the load-dependent regulation of renal tubular Na+ transport. To model this load dependency, apical Na+ entry was inhibited or stimulated for 18 h in A6 cells and vectorial transport was measured as short-circuit current (Isc) across monolayers on filter-bottom structures. Basal amiloride-sensitive Isc represents the activity of apical Na+ channels, whereas Isc after permeabilization of the apical membrane to cations with nystatin represents maximal activity of the basolateral Na(+)-K(+)-ATPase. Chronic inhibition of apical Na+ entry by 18-h apical exposure to amiloride or replacement of apical Na+ with tetramethylammonium (TMA+), followed by washing and restoration of normal apical medium, revealed a persistent decrease in Isc that remained despite exposure to nystatin. Both basal and nystatin-stimulated Isc recovered progressively after restoration of normal apical medium. In contrast, chronic stimulation of apical Na+ entry by short circuiting the epithelium increased Isc in the absence and presence of nystatin, indicating upregulation of both apical Na+ channels and basolateral Na(+)-K(+)-ATPase. Basolateral equilibrium [3H]ouabain binding was reduced to 67 +/- 5% in TMA+ vs. control cells, whereas values in 18-h short-circuited cells increased by 42 +/- 19%. The results demonstrate that load dependency of tubular Na+ transport can be modeled in vitro and indicate that the regulation of Na(+)-K(+)-ATPase observed in these studies occurs in part by changes in the density of functional transporter proteins within the basolateral membrane.

Galanin-induced alteration of electrolyte transport in the rat intestine

1992 ◽  
Vol 263 (4) ◽  
pp. G502-G507
Author(s):  
T. Kiyohara ◽  
M. Okuno ◽  
H. Ishikawa ◽  
T. Nakanishi ◽  
Y. Shinomura ◽  
...  
Keyword(s):  
Short Circuit ◽  
Short Circuit Current ◽  
Electrical Field Stimulation ◽  
Distal Colon ◽  
Rat Colon ◽  
Chloride Absorption ◽  
Neural Transmission ◽  
36Cl Fluxes ◽  
Intestinal Ion Transport

Effects of rat and porcine galanin on rat intestinal ion transport were examined in vitro. In the rat distal colon, a sustained increase in short-circuit current (Isc) was produced by the serosal addition of rat galanin at a concentration as low as 10(-9) M, and a maximal increment was observed at 10(-7) M. Porcine galanin was approximately 100 times less potent than rat galanin. In the rat jejunum, rat galanin produced only a slight and transient decrease in basal Isc. The response to rat galanin was not influenced by atropine, hexamethonium, or amiloride, but was virtually abolished by tetrodotoxin or furosemide. Rat galanin did not significantly influence the increase in Isc elicited by electrical field stimulation in the rat colon and jejunum. Transmural unidirectional 22Na and 36Cl fluxes in the rat colonic mucosa were measured under short-circuited conditions, and rat galanin significantly decreased net sodium and net chloride absorption. These findings suggest that galanin acts as a secretory modulator in the rat colon via noncholinergic neural transmission.

Defective modulation of colonic secretomotor neurons in a rabbit model of colitis

1993 ◽  
Vol 264 (4) ◽  
pp. G671-G677 ◽  
Author(s):  
J. M. Goldhill ◽  
R. Burakoff ◽  
V. Donovan ◽  
K. Rose ◽  
W. H. Percy
Keyword(s):  
Short Circuit ◽  
Rabbit Model ◽  
In Vitro Study ◽  
Short Circuit Current ◽  
Electrical Field Stimulation ◽  
Distal Colon ◽  
Trinitrobenzenesulfonic Acid ◽  
Cyclic Monophosphate ◽  
Secretomotor Neurons

The present in vitro study was conducted to investigate possible alterations in the control of colonic electrolyte transport in an experimental model of colitis. Intrarectal administration of trinitrobenzenesulfonic acid induced a colitis-like inflammation in the rabbit distal colon. Responses to amiloride and residual short-circuit current after this treatment were unchanged, suggesting that the absorptive and secretory mechanisms remained intact. Electrical field stimulation and vasoactive intestinal polypeptide, a candidate secretomotor neurotransmitter, both elicited similar responses in control and colitic tissue. This suggests that communication at the neuroepithelial junction was unimpaired. In untreated tissue, the effects of prostaglandin E2 (PGE2) and of acetylcholine were attenuated by tetrodotoxin, suggesting, therefore, that both play a role in the modulation of secretomotor neurons. In addition, PGE2 had an appreciable direct epithelial effect. Responses to both of these agonists were absent in colitis. The effects of N6,2'-O-dibutyryladenosine 3',5'-cyclic monophosphate were unchanged in colitis, suggesting that altered PGE2 responsiveness may involve changes in epithelial receptor number, affinity, or in their ability to mediate an increase in adenosine 3',5'-cyclic monophosphate levels. It is concluded that this rabbit model of colitis exhibits 1) defects in the modulation of secretomotor neurons by acetylcholine and PGE2 and 2) an attenuated epithelial response to PGE2.

Dietary flavonol quercetin induces chloride secretion in rat colon

1998 ◽  
Vol 275 (5) ◽  
pp. G1166-G1172 ◽  
Author(s):  
Rainer Cermak ◽  
Ursula Föllmer ◽  
Siegfried Wolffram
Keyword(s):  
Short Circuit ◽  
Ussing Chamber ◽  
Phosphodiesterase Inhibitor ◽  
Short Circuit Current ◽  
Distal Colon ◽  
Chloride Secretion ◽  
Proximal Colon ◽  
Rat Colon ◽  
Quercetin Glycoside

The aim of this study was to investigate the possible effects of the flavonol quercetin, the most abundant dietary flavonoid, on the intestinal mucosa. In vitro experiments were performed with various segments of the rat intestine, using the Ussing chamber technique. Quercetin increased the short-circuit current ( I sc) in the jejunum, ileum, and proximal and distal colon. Additional experiments were performed using preparations of the proximal colon. The maximum effective dose of quercetin was found to be ∼100 μM. The quercetin-induced increase in I sc was inhibited by the Cl− channel blocker 5-nitro-2-(3-phenylpropylamino)-benzoic acid. Adding blockers of the Na+-K+-2Cl−cotransporter to the serosal compartment diminished the increase of I sc due to quercetin. Ion substitution and flux measurements indicated that the effect of quercetin was due to electrogenic Cl− and[Formula: see text] secretion. In contrast to the aglycone, the quercetin glycoside rutin had no effect. The effect of quercetin on I scwas additive to the I sc increase induced by forskolin, but the flavonoid diminished the I sc evoked by carbachol. The phosphodiesterase inhibitor theophylline blocked the effect of quercetin. Genistein, a related isoflavone, did not alter the I sc evoked by quercetin. These findings demonstrate that the dietary flavonol quercetin induces Cl−secretion and most likely [Formula: see text]secretion in rat small and large intestine. The effects are restricted to the flavonol aglycone.

Acid secretion in fetal rat stomach in vitro

1981 ◽  
Vol 240 (3) ◽  
pp. G206-G210
Author(s):  
R. Ducroc ◽  
J. F. Desjeux ◽  
B. Garzon ◽  
J. P. Onolfo ◽  
J. P. Geloso
Keyword(s):  
Short Circuit ◽  
Short Circuit Current ◽  
Rat Stomach ◽  
Passive Permeability ◽  
Anion Secretion ◽  
Ussing Chambers ◽  
Ionic Fluxes ◽  
Fetal Rat

In vivo fetal rat stomach produces HCl 48 h before birth. This study examines the mechanisms of H+ secretion from days 19 to 21 before birth. Isolated fetal stomachs were mounted as flat sheets in Ussing chambers for measurement of the transepithelial H+ fluxes (JH+) and short-circuit current (Isc), as indexes of the active ionic fluxes, and for measurement of total ionic conductance (G) and unidirectional mannitol fluxes from serosa to mucosa (JMans leads to m), as indexes of passive permeability. The results indicate that JH+ was absent at day 19 but reached 0.75 +/- 0.1 and 0.75 +/- 0.09 mueq . h-1 . cm-2 at days 20 and 21, respectively. Concomitantly, Isc increased significantly (56%) between days 19 and 20 in the direction of anion secretion or cation absorption. Parallel reductions in G (45%) and in JMans leads to m (66%) were observed between days 19 and 20. In conclusion, the simultaneous appearance of active H+ secretion and decreased passive transepithelial permeability strongly suggests that both processes are involved in the mechanism of acidification of the fetal rat stomach before birth.

Enzyme- and mineralocorticoid receptor-controlled electrogenic Na+ absorption in human rectum in vitro

1995 ◽  
Vol 269 (1) ◽  
pp. G42-G48 ◽  
Author(s):  
H. J. Epple ◽  
J. D. Schulzke ◽  
H. Schmitz ◽  
M. Fromm
Keyword(s):  
Short Circuit ◽  
Short Circuit Current ◽  
Distal Colon ◽  
Hill Coefficient ◽  
Complete Control ◽  
Human Rectum ◽  
In The Beginning ◽  
Mineralocorticoid Activity

In vivo electrogenic Na+ absorption (JeNa) in the human rectum is controlled by acute variation of aldosterone in nanomolar concentration range. In this study we report both the induction of JeNa in human rectum epithelium by nanomolar aldosterone added in vitro and the enzymatic control of glucocorticoid action on JeNa. JeNa was measured as amiloride-sensitive short-circuit current 8 h after addition of the respective steroid. Aldosterone (10 nM) caused JeNa of 5.7 +/- 1.4 mumol.h-1.cm-2. Cortisol in the same concentration did not induce significant JeNa. Because cortisol is readily inactivated by 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), the true mineralocorticoid activity of cortisol was evaluated after inhibition of 11 beta-HSD by carbenoxolone. Carbenoxolone alone did not exhibit mineralocorticoid activity. If cortisol (10 nM) was given together with carbenoxolone (1 microM), the resulting JeNa (4.5 +/- 0.4 mumol.h-1.cm-2) was not significantly different from that after 10 nM aldosterone, indicating equal intrinsic mineralocorticoid activity of cortisol and aldosterone. The same mechanisms were found in rat late distal colon. Kinetic data of carbenoxolone at 10 nM cortisol resulted in a Michaelis constant of 0.3 microMs, maximal absorption of 8.4 mumol.h-1.cm-2, and a Hill coefficient of 1.8. The effects of carbenoxolone and glycyrrhetinic acid did not differ. We conclude that JeNa is under complete control of mineralocorticoid action. "Spontaneous" JeNa in the beginning of the in vitro period can be explained by elevated steroid levels before tissue removal.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride-sensitive salt and fluid absorption in small intestine of sodium-depleted rats

1985 ◽  
Vol 248 (1) ◽  
pp. G133-G141 ◽  
Author(s):  
P. C. Will ◽  
R. N. Cortright ◽  
R. G. Groseclose ◽  
U. Hopfer
Keyword(s):  
Small Intestine ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Distal Colon ◽  
Proximal Colon ◽  
Salt Transport ◽  
Fluid Absorption ◽  
Major Pathway

Secondary hyperaldosteronism produced by Na+ depletion was associated with increases in salt and fluid absorption in both the small intestine and the distal colon but not in the cecum and the proximal colon. Because these changes had not been documented for the small intestine, this study focused on the regulation of this tissue. Increased NaCl and water absorption was expressed in vitro by increases in short-circuit current and transepithelial potential and in vivo by increased fluid absorption and a decreased luminal content of Na+ and water. For example, the short-circuit current in the ileum of Na+-depleted rats was 2-fold that of adrenalectomized and 1.3-fold that of adrenal-intact control animals. The short-circuit current was inhibitable 24 +/- 14% by micromolar concentrations of amiloride in Na+-deficient animals compared with 1 +/- 3% in control animals. Similarly, ileal fluid absorption in vivo was 2.3-fold higher in Na+-deficient relative to control animals. The additional fluid absorption was sensitive to 50 microM amiloride, whereas amiloride had no effect in control animals. Furthermore, the Na+ content of the chyme from the ileum of Na+-deficient animals was about half that of controls. These results suggest that mineralocorticoids can induce the amiloride-sensitive Na+ transporter in the small intestine and that this type of epithelial salt transport can become a major pathway for salt retention by the small intestine.

Metabolic Support of Chloride-dependent Short-circuit Current Across Locust Rectum

1982 ◽  
Vol 99 (1) ◽  
pp. 349-362
Author(s):  
M. CHAMBERLIN ◽  
J. E. PHILLIPS
Keyword(s):  
Cyclic Amp ◽  
Short Circuit ◽  
Malpighian Tubule ◽  
Short Circuit Current ◽  
Metabolic Substrates ◽  
Endogenous Substrates ◽  
Tubule Fluid ◽  
Substrate Source ◽  
Stimulation Of

1. Recta of desert locusts were short-circuited and depleted of endogenous substrates by exposing them to saline containing cyclic AMP but no metabolites. Individual substrates were then added to substrate-depleted recta and the change in short-circuit current (Isc) monitored. 2. Proline or glucose (50 mM) caused by far the largest increase in Isc of all substrates tested. Stimulation of the Isc by proline was not dependent upon external sodium, but did require external chloride. 3. Physiological levels of proline also caused a large increase in Isc, while physiological levels of glucose produced a much smaller stimulation. Over 90% of the proline-dependent Isc stimulation can be produced by adding 15 mM proline solely to the lumen side of the tissue. 4. These results are discussed with regard to rectal oxidative metabolism and availability of metabolic substrates in vivo. High levels of proline in Malpighian tubule fluid are probably the major substrate source for rectal Cl−transport. Note:

Apical nonspecific cation conductances in rabbit cecum

1994 ◽  
Vol 266 (3) ◽  
pp. G475-G484 ◽  
Author(s):  
J. H. Sellin ◽  
W. P. Dubinsky
Keyword(s):  
Epithelial Transport ◽  
Apical Membrane ◽  
Divalent Cations ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Distal Colon ◽  
Na Channel ◽  
Similar Response ◽  
Electrogenic Transport

Rabbit cecum exhibits electrogenic Na absorption in vitro. However, because this transport process is not inhibited by amiloride nor does it demonstrate saturation kinetics typical of the amiloride-inhibitable Na channel, we considered whether the cecal transporter represented one of a recently described family of nonselective cation conductances or channels (NSCC). Both transepithelial and vesicle studies demonstrated that K, Cs, and Rb were transported via an apical conductance. Electrogenic transport was inhibited by divalent cations including Ca, Mg, and Ba but was unaffected by either lanthanum or gadolinium. Parallel studies in distal colon did not exhibit a similar response to either K substitution or Ba inhibition. Phenamil, verapamil, and nicardipine significantly inhibited the short-circuit current (Isc). stimulated by nominal Ca- and Mg-free conditions. Flux studies demonstrated a correlation between changes in Isc and Na transport. Microelectrode impalement studies suggested that there may be both NSCC and K conductance in the apical membrane. Planar bilayer studies identified a 190-pS cation channel that may correlate with the macroscopic transport properties of this epithelium. These studies are consistent with a model of cecal Na absorption mediated by a NSCC in the apical membrane; this may be the mechanism underlying the distinct epithelial transport characteristics of this intestinal segment.

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