Effect of acetazolamide on sodium and chloride transport by in vitro rabbit ileum

1975 ◽  
Vol 228 (6) ◽  
pp. 1808-1814 ◽  
Author(s):  
HN Nellans ◽  
RA Frizzell ◽  
SG Schultz

Acetazolamide (8 mM) aboishes active Cl absorption and inhibits but does not abolish active Na absorption by stripped, short-circuited rabbit ileum. These effects are not accompanied by significant changes in the transmural electrical potential difference or short-circuit current. Studies of the undirectional influxes of Na andCl indicate that acetazolamide inhibits the neutral, coupled NaCl influx process at the mucosal membranes. This action appears to explain the observed effect of acetazolamide on active, transepithelial Na and Cl transport. Acetazolamide did not significantly inhibit either spontaneous or theophylline-induced Cl secretion by this preparation, suggesting that the theophylline-induced secretion may not simply be due tothe unmasking of a preexisting efflux process when the neutral influx mechanism is inhibited by theophylline. Finally, inhibition of the neutral NaCl influx process by acetazolamide does not appear to be attributable to an inhibition of endogenous HCO3production or an elevation in intracellular cyclic-AMP levels. Instead, it appearstheat the effect of acetazolamide is due to a direct interaction with a membrane component involved in the coupled influx process.

1989 ◽  
Vol 77 (2) ◽  
pp. 161-166 ◽  
Author(s):  
K. J. Moriarty ◽  
N. B. Higgs ◽  
M. Woodford ◽  
L. A. Turnberg

1. Cholera toxin stimulates intestinal secretion in vitro by activation of mucosal adenylate cyclase. However, it has been proposed that cholera toxin promotes secretion in vivo mainly through an indirect mechanism involving enteric neural reflexes. 2. We examined this hypothesis further by studying the influence of neuronal blockade on cholera toxin-induced changes in fluid transport across rabbit ileum in vitro. Mucosa, stripped of muscle layers, was mounted in flux chambers and luminal application of crude cholera toxin (2 μg/ml) caused a delayed but sustained rise in the short-circuit current, electrical potential difference and Cl− secretion. Pretreatment with the nerve-blocking drug, tetrodotoxin (5 × 10−6 mol/l serosal side), failed to influence the secretory response to cholera toxin, and addition of tetrodotoxin at the peak response to cholera toxin also had no effect. 3. That tetrodotoxin could block neurally mediated secretagogues was confirmed by the demonstration that the electrical responses to neurotensin (10−7 mol/l and 10−8 mol/l) were blocked by tetrodotoxin (5 × 10−6 mol/l). Furthermore, the response to cholera toxin of segments of ileum, which included the myenteric, submucosal and mucosal nerve plexuses, was not inhibited by tetrodotoxin. 4. We conclude that cholera toxin-induced secretion in rabbit ileum in vitro is not mediated via a neurological mechanism.


1982 ◽  
Vol 97 (1) ◽  
pp. 197-216
Author(s):  
J. C. Cornell

1. Measurements of electrical potential difference (PD), short-circuit current (SCC) and unidirectional fluxes of sodium and chloride were made across portions of the intestine. Based on the results, the intestine can be divided into at least four physiologically distinct regions. 2. These four physiological regions, designated from anterior to posterior as R I-II, R III A, R III B and R IV, do not completely correspond to the four anatomically distinct regions of the intestine. 3. The PD (serosal side positive) in R I-II, R III A, R III B and R IV is 1.08, 12.4, 5.61 and 31.7 mV, respectively. 4. The SCC in these same regions is 9.9, 50.4, 49.7, and 16.4 micro A cm2, respectively. 5. When short-circuited, net sodium and net chloride fluxes in the above regions are −0.36 and −0.27, 1.46*** and −0.92*, 1.74*** and −0.06 and 1.01*** and 0.07 mumol cm-2 h-1, respectively. Positive fluxes indicate net mucosal to serosal movements and asterisks indicate significant net fluxes (* P less than 0.05, *** P less than 0.001). 6. There is good agreement between the SCC and net sodium transport in R III B. In the other regions of the intestine the ionic basis of the SCC has not been completely explained. 7. The properties of the intestine in vitro appear to make the intestine well suited for the task of conserving sodium, a function which the intestine performs in vivo.


1981 ◽  
Vol 240 (3) ◽  
pp. G211-G216
Author(s):  
K. A. Hubel

To obtain additional evidence that the Cl secretion caused by electrical field stimulation (EFS) in rabbit ileum in vitro is mediated by nerves or amine precursor uptake and decarboxylation (APUD) cells, we determined whether the response could be prevented by agents that depolarize nerves, veratrine or 50 mM K. EFS 1) increased transmural electrical potential difference (PD) and the short-circuit current (Isc) and reduced total ion conductivity (G), 2) caused Cl secretion by reducing the mucosal-to-serosal flow of chloride (JClm leads to s) alone or in combination with an increase in the serosal-to-mucosal flux of chloride (JCls leads to m), and 3) reduced Na absorption or caused secretion by increasing JCls leads to m alone or in association with a reduction in JNam leads to s. At 10(-5) g/ml, veratrine prevented the changes in ionic fluxes caused by EFS and reduced the PD and Isc. It did not reduce the Isc response to 5 mM aminophylline, however. Fifty millimolar K decreased PD and Isc and increased G. JNam leads to s and JNas leads to m diminished in proportion to the reduction in bath Na concentration, so the net flux of sodium (JNanet) was not affected. JClnet did not change, although both JClm leads to s and JCls leads to m increased. Fifty millimolar K prevented the changes in ionic fluxes caused by EFS and reduced the Isc response to aminophylline by half. The study provides additional evidence that the effects of EFS are mediated by nerves or electrically excitable APUD cells, but the contribution of each is uncertain.


1975 ◽  
Vol 67 (1) ◽  
pp. 119-125
Author(s):  
P. J. BENTLEY

SUMMARY The electrical potential difference and short-circuit current (scc, reflecting active transmural sodium transport) across the toad urinary bladder in vitro was unaffected by the presence of hypo-osmotic solutions bathing the mucosal (urinary) surface, providing that the transmural flow of water was small. Vasopressin increased the scc across the toad bladder (the natriferic response), but this stimulation was considerably reduced in the presence of a hypo-osmotic solution on the mucosal side, conditions under which water transfer across the membrane was also increased. This inhibition of the natriferic response did not depend on the direction of the water movement, for if the osmotic gradient was the opposite way to that which normally occurs, the response to vasopressin was still reduced. The natriferic response to cyclic AMP was also inhibited in the presence of an osmotic gradient. Aldosterone increased the scc and Na+ transport across the toad bladder but this response was not changed when an osmotic gradient was present. The physiological implications of these observations and the possible mechanisms involved are discussed.


1978 ◽  
Vol 44 (6) ◽  
pp. 900-904 ◽  
Author(s):  
M. G. Marin ◽  
M. M. Zaremba

Active transport of Cl- toward the tracheal lumen and Na+ away from the lumen creates an electrical potential difference across dog tracheal epithelium. This study examined in vitro the effect of varying calcium concentration in the bathing media on the ion transport and electrical properties of dog tracheal epithelium. In six pairs of epithelia, changing calcium concentration from 1.9 to 0 mM resulted in a significant decrease in electrical resistance, from 318 +/- 36 to 214 +/- 24 omega.cm2. Short-circuit current and net Cl- and Na+ fluxes measured under short-circuit conditions were not changed significantly. Changing calcium concentration from 1.9 to 10 mM resulted in no significant change from control in the electrical properties nor in net Cl- and Na+ fluxes (short-circuit conditions). Histamine (10(-4) M) produced a significantly smaller increase in short-circuit current in 0 than in 1.9 mM Ca2+ (+5 +/- 2 vs. +12 +/- 2 microamperemeter/cm2). However, electrical changes were not significantly different in 1 or 10 mM Ca2+. These results indicate that calcium lack increased permeability of tracheal epithelium and that the increase in short-circuit current due to histamine depended in part on calcium.


1980 ◽  
Vol 239 (3) ◽  
pp. R285-R290
Author(s):  
E. Skadhauge ◽  
T. J. Dawson

The lower intestine (coprodeum and colon) of the Australian parrot, the galah, was mounted in Ussing chambers. Short-circuit current (SCC), electrical potential difference (PD), and unidirectional fluxes of Na and Cl were measured in birds that were fed mixed seeds or were NaCl loaded. The net Na transport of both coprodeum and colon was nearly equal to the SCC, and the flux ratio for Cl was unity. In birds which received mixed seeds, average coprodeal Na transport was 7.8 mu eq . cm-2 . h-1, and PD was 19 mV. The Km for Na was 5.7 meq/l. In colon, Na transport was reduced by 67% and PD by 70%. The ratio between unidirectional Na and Cl fluxes in the serosa-mucosa direction was 0.7. Salt loading suppressed coprodeal, but increased colonic Na transport. The coprodeal and colonic SCC and NA transport of birds receiving mixed seeds were inhibited by amiloride on the mucosal side. Colonic SCC of NaCl-loaded birds was only slightly reduced by amiloride (by 17%), but stimulated by amino acids (by 18%).


1976 ◽  
Vol 231 (2) ◽  
pp. 501-508 ◽  
Author(s):  
TL Mullen ◽  
M Kashgarian ◽  
D Biemesderfer ◽  
GH Giebisch ◽  
TU Biber

The urinary bladder of Amphiuma exhibits stable transport properties and an electrical potential difference in vitro. The lumen is significantly negative to the serosa and under short-circuited conditions flux rations for Na and Cl of 5.92 +/- 0.42 and 1.81 +/- 0.20, respectively, were observed. The close agreement between the short-circuit current and net Na flux suggests that most, if not all, of the current is carried by Na. Both ouabain and amiloride decreased the short-circuit current and the mucosal-to-serosal (M leads to S) flux of Na. Furosemide caused a transient increase in the M leads to S flux of Na and Cl but ADH was without effect. In bladders that had high transmural resistance, a net movement of K in the M leads to S direction under short-circuited conditions with flux ratios of up to 2 could be observed. The epithelium of the Amphiuma bladder consists of three cell types: granular cells, basal cells, and mitochondria-rich cells. No goblet cells are present. The mitochondria-rich cells comprise less than 5% of the population of the surface epithelium in Amphiuma in contrast to other amphibian bladders, where it accounts for up to 25% of the population.


1987 ◽  
Vol 253 (2) ◽  
pp. G211-G216
Author(s):  
B. R. Grubb ◽  
P. J. Bentley

Transmural electrical potential difference, short-circuit current (Isc), and resistance were measured in vitro in the intestines of chickens. In birds maintained on a low-Na diet, there was a rise in Isc in the ileum and the colon but not in the duodenum or jejunum. A substantial portion of this Isc could be inhibited by the Na channel-blocking drug, amiloride. The low-Na diet results in elevated plasma levels of aldosterone and the effects of the diet on intestinal transport could be mimicked by administration of this hormone. The time course of the effects of these two treatments on the ileum and colon were quite different, as a much longer exposure was needed to elicit maximal effects in the ileum than in the colon, possibly due to the presence of two types of adaptation mechanisms. The responses observed may reflect an adaptation of mechanisms for increasing Na transport from the intestine. The presence of such a mechanism in the vertebrate ileum has until recently been in doubt.


1976 ◽  
Vol 231 (5) ◽  
pp. 1546-1549 ◽  
Author(s):  
MG Marin ◽  
B Davis ◽  
JA Nadel

Electrical potential difference is generated across canine tracheal epithelium by active transport of Cl- toward and Na+ away from the lumen. The present study examines the effects of acetylcholine on short-circuit current, potential difference, resistance, and fluxes of 36Cl and 24Na measured across pieces of canine tracheal epithelium mounted in Ussing-type chambers. Under short-circuit conditions, acetylcholine (5 X 10(-5) M) increased significantly net ion flux toward the lumen of Cl- (n equals 7) from +1.7 +/- SE 0.5 TO +3.3 +/- SE 0.5 mueq/cm2 - h, and of Na+ (n equals 7) from -0.8 +/- SE 0.2 to +0.5 +/- SE 0.2 mueq/cm2 - h. Under open-circuit conditions, acetylcholine (5 X 10(-5) M) increased significantly the unidirectional flux of Cl- (n equals 6) toward the lumen from 4.7 +/- SE 1.3 to 5.9 +/- SE 1.4 mueq/cm2 - h, while the other measured fluxes did not change significantly, suggesting that net Cl- flux had increased toward the lumen. Atropine sulfate (10(-8) M) prevented the response to acetylcholine (5 X 10(-5) M). The increased ion flux due to acetylcholine may mediate water secretion into the airway lumen, and this secretion may have important effects on the physical properties of the liquid through which the respiratory cilia beat.


1987 ◽  
Vol 253 (4) ◽  
pp. F613-F621 ◽  
Author(s):  
N. Y. Marcus ◽  
D. C. Marcus

The isolated nonsensory region of the gerbil utricle in vitro produced a lumen-positive transepithelial electrical potential difference (VT) of +5.7 mV and a luminal fluid containing 106 mM K when bathed in mammalian Ringer solution (5 mM K and 150 mM Na). The lumen of this region was perfused in vitro with K-free solution and the luminal [K], VT, and transepithelial resistance (RT) were measured before and following perfusion under control conditions and after addition of bumetanide (0.1 mM) or ouabain (1 mM) to the bath. The perfusate contained a reduced [Ca], since the average value of utricular endolymph in vivo (0.28 +/- 0.03 mM) measured with Ca-selective microelectrodes was 38% of that in perilymph. Under control conditions, the luminal [K] initially increased at a rate of 2.13 mumol X cm-2 X h-1 after perfusion; net secretion continued until the luminal [K] returned to its preperfusion level. This flux rate corresponds to 57 microA/cm2. The “equivalent short-circuit current” (Equiv. Isc; VT/RT) was found to average 61 microA/cm2. Both K secretion and VT were fully inhibited by bumetanide and by ouabain. Luminal application of Ba (5 mM) in K-free solution had no effect on the initial rate of K secretion, but did prevent full recovery of luminal [K] to the control level. These results are the first estimates of K secretion by the nonsensory cells of the utricle and are the first to directly demonstrate inhibition of K secretion in the inner ear by bumetanide and in the nonsensory tissue of the utricle by ouabain.


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