Effects of "loop" diuretics on ion transport by dog tracheal epithelium

1983 ◽  
Vol 245 (5) ◽  
pp. C388-C396 ◽  
Author(s):  
J. H. Widdicombe ◽  
I. T. Nathanson ◽  
E. Highland
Keyword(s):  
Ion Transport ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Loop Diuretics ◽  
Tracheal Epithelium ◽  
Isolated Cells ◽  
Significant Fall ◽  
Cl Transport ◽  
Site Of Action ◽  
Net Flux

The "loop" diuretics MK-196, bumetanide, piretanide, and furosemide are all potent inhibitors of Cl transport by the dog's tracheal epithelium. In short-circuited tissues, the drugs caused significant decreases in both unidirectional Cl fluxes and in the net flux of Cl toward the lumen; the change in net Cl flux was not significantly different from the change in short-circuit current. The drugs had no effect on active Na absorption. All drugs caused a significant fall in tissue conductance. All drugs, except MK-196, were more potent from the serosal bath; MK-196 was equipotent from either side of the tissue. In experiments with isolated cells, the diuretics caused no significant changes in intracellular Na and K concentrations, a fall in intracellular Cl concentration, and approximately equal falls in Na and Cl influxes. These results suggest that the site of action of these drugs is on a basolateral linked Na-Cl entry process. Additional evidence for such a linked entry process was provided by experiments in which removal of Cl reduced Na influx and removal of Na reduced Cl influx.

Effect of ethanol on ion transport and electrical properties of dog trachea in vitro

1983 ◽  
Vol 54 (5) ◽  
pp. 1335-1339 ◽  
Author(s):  
F. D. McCool ◽  
J. P. Zorn ◽  
M. G. Marin
Keyword(s):  
Electrical Properties ◽  
Ion Transport ◽  
Short Circuit ◽  
Electrical Potential ◽  
Short Circuit Current ◽  
Tracheal Epithelium ◽  
Electrical Potential Difference ◽  
Net Flux ◽  
Circuit Technique

We studied the effect of ethanol on the electrical and ion transport properties of dog tracheal epithelium using Ussing's short-circuit technique. There was a significant reduction of short-circuit current and electrical potential difference and a tendency of electrical resistance to increase in response to increasing concentrations of ethanol in the bathing solutions. Threshold changes in the electrical properties were noted at an ethanol concentration of 3.3 microliter/ml (260 mg/100 ml). Ethanol did not produce these changes in electrical properties when Cl- and Na+ were substituted in the bathing media with either choline or SO2-(4). In five paired tissue preparations, ethanol (13.3 microliters/ml) significantly reduced the net flux of Cl- toward the lumen from 2.68 +/- 0.62 to 1.00 +/- 0.69 (SE) mu eq X cm-2 X h-1, due primarily to a reduced unidirectional flux of Cl- from submucosa to lumen. These observations demonstrate that ethanol has an effect on the ion transport and electrical properties of dog tracheal epithelium at concentrations that may be of clinical relevance.

Na and Cl Transport across the Isolated Anterior Intestine of the Plaice Pleuronectes Platessa

1981 ◽  
Vol 90 (1) ◽  
pp. 123-142
Author(s):  
M. M. P. RAMOS ◽  
J. C. ELLORY
Keyword(s):  
Chloride Transport ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Negative Potential ◽  
Loop Diuretics ◽  
Significant Part ◽  
Cl Transport ◽  
Anterior Intestine ◽  
Short Circuit Currents ◽  
Na Uptake

1. The tissue was found to have a serosa negative potential, and short-circuit currents equivalent to the net Cl transport. 2. A significant part of the Cl uptake was Na dependent and a similar fraction of the Na uptake was Cl dependent. 3. Short-circuit current and uptake of both ions were inhibited by loop diuretics and analogues. 4. I80 and P.D. were abolished by ouabain. 5. The observations are consistent with the idea of a coupled NaCl entry into the cell, using the energy inherent in the Na gradient; Na being pumped out of the cells by the Na pump and followed electrically by Cl−. Net chloride transport and the serosa negative potential would be a consequence of the permselective properties of the junctions allowing Na but not Cl to recycle back to the mucosal solution.

Suppression of gastric acid secretion by furosemide in isolated gastric mucosa of guinea pig

1980 ◽  
Vol 239 (6) ◽  
pp. G532-G535 ◽  
Author(s):  
A. Ayalon ◽  
A. Corcia ◽  
G. Klemperer ◽  
S. R. Caplan
Keyword(s):  
Guinea Pig ◽  
Acid Secretion ◽  
Short Circuit ◽  
Basolateral Membrane ◽  
Electrical Conductance ◽  
Short Circuit Current ◽  
Cl Transport ◽  
Consequent Reduction ◽  
Net Flux ◽  
Mucosal Side

The effect of furosemide on acid secretion and Cl- transport was studied in isolated fundic mucosa of the guinea pig. Furosemide (10(-3) M), applied to the serosal side produced an immediate effect on the short-circuit current (Isc), lowering it by 47 +/- 2%. Potential difference decreased by 29 +/- 3%, electrical conductance by 18 +/- 4%, acid secretion by 38 +/- 1%, and net flux of Cl- from serosal-to-mucosal side by 37%. Application of the drug to the mucosal side produced similar effects on acid secretion and on the electrical parameters. It is suggested that furosemide blocks the entrance of Cl-, by the Na+--Cl- cotransport mechanism, through the basolateral membrane of the secreting cell. The consequent reduction in electrogenic Cl- transport would cause Isc and acid secretion to decrease. A reduction of Cl- conductance of the apical membrane, upon mucosal application of the drug, would cause similar effects on acid secretion and Cl- transport.

Effect of calcium on ion transport and electrical properties of tracheal epithelium

1978 ◽  
Vol 44 (6) ◽  
pp. 900-904 ◽  
Author(s):  
M. G. Marin ◽  
M. M. Zaremba
Keyword(s):  
Electrical Properties ◽  
Ion Transport ◽  
Calcium Concentration ◽  
Short Circuit ◽  
Electrical Potential ◽  
Short Circuit Current ◽  
Tracheal Epithelium ◽  
Electrical Potential Difference ◽  
Tracheal Lumen

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.

Regulation of Na-Cl absorption in rabbit proximal colon in vitro

1987 ◽  
Vol 252 (1) ◽  
pp. G45-G51 ◽  
Author(s):  
J. H. Sellin ◽  
R. De Soignie
Keyword(s):  
Ion Transport ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Proximal Colon ◽  
Beta Agonist ◽  
Disulfonic Acid ◽  
Low Concentrations ◽  
Cotransport System ◽  
Net Flux

Ion transport in rabbit proximal colon (PC) in vitro is dominated by a Na-Cl cotransport system stimulated by epinephrine. To further characterize the regulation of Na-Cl transport, we tested the effects of specific adrenergic agonists on ion fluxes under short-circuit conditions. Additionally, we tested the effects of the transport inhibitors bumetanide, furosemide, and 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS). Basal Na and Cl absorption were essentially nil [Na net flux (JNanet) = 0.3 +/- 0.4, and Cl net flux (JClnet) = -0.5 +/- 0.5 mu eq X cm-2 X h-1, means +/- SE]. The alpha 2-agonist clonidine significantly increased net Na and Cl absorption (delta JNanet = 3.0 +/- 0.6 mu eq X cm-2 X h-1, delta JClnet = 2.0 +/- 0.4 mu eq X cm-2 X h-1) with a minimal change in short-circuit current (delta Isc = 0.1 +/- 0.1 mu eq X cm-2 X h-1). The alpha 1-agonist phenylephrine and the beta-agonist isoproterenol did not alter ion transport. The alpha 2-blocker yohimbine (YOH) had a complex, concentration-dependent effect. At low concentrations (10(-6)-10(-8) M) YOH effectively inhibited epinephrine-stimulated cotransport. Compared with 10(-8)M YOH, 10(-6) YOH blocked 90% of the epinephrine-induced increases in Na and Cl absorption.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrophysiological properties of guinea pig tracheal epithelium determined by cable analysis

1993 ◽  
Vol 265 (1) ◽  
pp. L38-L44
Author(s):  
T. L. Croxton
Keyword(s):  
Guinea Pig ◽  
Ion Transport ◽  
Short Circuit ◽  
Electrical Potential ◽  
Short Circuit Current ◽  
Tracheal Epithelium ◽  
Sodium Absorption ◽  
Luminal Diameter ◽  
Cable Analysis

Electrophysiological characteristics of guinea pig tracheae were measured in vitro using an adaptation of cable analysis. This method allowed the repeated measurement of luminal diameter and epithelial electrical potential, resistance, and short-circuit current (Isc) during treatments known to affect smooth muscle contraction and epithelial ion transport. Stable values taken 3 h after mounting were as follows: diameter, 2.27 +/- 0.10 mm; potential, -28.3 +/- 2.3 mV; resistance, 327 +/- 30 omega.cm2; and Isc, 91.2 +/- 6.8 microA/cm2. These electrophysiological results are comparable to reported values for other species. However, the resistance and potential obtained in this study were larger than those previously reported for the guinea pig. Tracheal diameter was decreased 15% by methacholine and was increased 43% by subsequent isoproterenol treatment. Isoproterenol caused a small but significant increase in Isc when this quantity was normalized to tracheal length rather than to the apparent surface area. In contrast, apical amiloride decreased Isc by 51% and did not change diameter. These data validate this implementation of cable analysis, demonstrate that sodium absorption is the predominant mechanism of active ion transport by guinea pig tracheal epithelium, and indicate that this tissue has little capacity for stimulated chloride secretion.

Effect of loop diuretics on bullfrog cornea epithelium

1989 ◽  
Vol 256 (4) ◽  
pp. C750-C755 ◽  
Author(s):  
W. Nagel ◽  
G. Carrasquer
Keyword(s):  
Apical Membrane ◽  
Short Circuit ◽  
Membrane Conductance ◽  
Short Circuit Current ◽  
Loop Diuretics ◽  
Cl Transport ◽  
Before And After ◽  
The Difference ◽  
Cornea Epithelium

The effect of loop diuretics on Cl transport was studied on an in vitro preparation of the bullfrog cornea. Bumetanide (10(-4) M) or furosemide (10(-3) M) added to the stromal solution decreased Cl transport measured as the short-circuit current (Isc) to values near zero. Concomitantly, transepithelial conductance (gt) decreased, whereas the intracellular potential (Vo) hyperpolarized and the fractional resistance of the apical membrane (fRo) increased. Substitution of SO4 for Cl in the tear-side solution led to prompt changes in Isc, gt, Vo, and fRo, characteristic of appreciable passive Cl movement across the apical membrane before and after inhibition. Epinephrine (10(-4) M) was similarly effective on apical membrane conductance in inhibited tissues as under control conditions, but the effective electromotive force for transepithelial Cl transport was reduced to approximately 25%. Intracellular Cl activity, measured with ion-selective microelectrodes, decreased so much that the difference in electrochemical Cl potential divided by the Faraday constant (delta mu Cl/F) was close to zero after inhibition of Isc by bumetanide. Apical Cl permeability remained essentially unchanged. Accordingly, loop diuretics inhibit Cl transport in the Cl-secreting cornea epithelium by blocking the Na-Cl symport without secondary apical effects, as believed for other Cl-reabsorbing epithelia.

Regional adrenergic regulation of ion transport across the isolated porcine gallbladder

1993 ◽  
Vol 264 (4) ◽  
pp. R703-R707 ◽  
Author(s):  
M. D. Duvall ◽  
S. M. O'Grady
Keyword(s):  
Ion Transport ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Ringer Solution ◽  
Gallbladder Epithelium ◽  
Adrenergic Agonist ◽  
Ussing Chambers ◽  
Cl Transport ◽  
Beta Agonists ◽  
Beta 2

The regional transport properties of the porcine gallbladder epithelium were studied using Ussing chambers in which tissues were bathed in porcine Ringer solution. Under basal conditions, tissues from the neck absorbed Na and Cl. Fundic tissues also absorbed Na, but net Cl transport was not different from zero. Serosal norepinephrine (NE; 0.1 microM) stimulated Na and Cl absorption in the neck but only Cl absorption in the fundus. The effects of NE on Na and Cl transport were blocked by pretreatment with yohimbine, suggesting that alpha 2-adrenoceptors mediate the transport-related actions of this neurotransmitter. Serosal isoproterenol (0.1 microM) produced a tetrodotoxin-insensitive, propranolol-sensitive increase in the short-circuit current (Isc) in fundic tissues but not in tissues from the neck. The beta 2-adrenergic agonist salbutamol produced a response similar to that of isoproterenol. However, the beta 1-adrenergic agonist dobutamine had no effect. Isoproterenol was 5.8-fold more potent than salbutamol in increasing the Isc. A possible explanation for the regional effects of beta-agonists is that beta-adrenoceptors are localized to epithelial cells in the fundic region. These results and results obtained previously suggest regional differences in basal Na and Cl transport across the porcine gallbladder epithelium and that both alpha 2- and beta 2-adrenoceptors act to regulate ion transport in this tissue.

Effects of mast cell-derived mediators on epithelial cells in canine trachea

1986 ◽  
Vol 251 (3) ◽  
pp. C387-C394 ◽  
Author(s):  
S. C. Lazarus ◽  
L. J. McCabe ◽  
J. A. Nadel ◽  
W. M. Gold ◽  
G. D. Leikauf
Keyword(s):  
Mast Cell ◽  
Ion Transport ◽  
Short Circuit ◽  
Calcium Ionophore ◽  
Short Circuit Current ◽  
Calcium Ionophore A23187 ◽  
Tracheal Epithelium ◽  
Sodium Absorption ◽  
Ionophore A23187 ◽  
Mastocytoma Cells

We examined the interaction between mast cell-derived mediators and the electrical and ion transport properties of canine tracheal epithelium. We compared the effect of mediators released by immunologic challenge of sensitized lung parenchyma with that of mediators released from canine mastocytoma cells challenged with calcium ionophore A23187. Short-circuit current (Isc) increased by 19.2 +/- 3.0 microA/cm2 in response to mediators released from sensitized lung fragments challenged with ragweed antigen. This effect was not due to histamine. When the epithelial tissues were pretreated with indomethacin, the same mediator supernatant increased Isc by only 3.8 +/- 4.3 microA/cm2. The mediators released from 10(7) mastocytoma cells challenged with calcium ionophore increased Isc by 25.1 +/- 13.6 microA/cm2. In the presence of indomethacin, the Isc increased by 2.0 +/- 0.4 microA/cm2. Mastocytoma-derived mediators produced an increase in net chloride secretion without a significant effect on net sodium absorption. This study provides direct evidence that mast cell-derived mediators can stimulate epithelial ion transport in canine trachea and suggests that the effect is indirect and dependent on intact cyclooxygenase pathways in the tracheal epithelium.

Paths of ion transport across canine fetal tracheal epithelium

1988 ◽  
Vol 65 (6) ◽  
pp. 2376-2382 ◽  
Author(s):  
C. U. Cotton ◽  
R. C. Boucher ◽  
J. T. Gatzy
Keyword(s):  
Ion Transport ◽  
Secretory Pathway ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Tracheal Epithelium ◽  
Rectal Gland ◽  
Pulmonary Epithelium ◽  
Fetal Sheep ◽  
Transport Pathways ◽  
Cl Secretion

Fluid secretion by the fetal sheep lung is thought to be driven by secretion of Cl- by the pulmonary epithelium. We previously demonstrated Cl- secretion by tracheal epithelium excised from fetal dogs and sheep. In this study we characterized the ion transport pathways across fetal canine tracheal epithelium. The transport of Na+ and Cl- across trachea excised from fetal dogs was evaluated from transepithelial electrical properties and isotope fluxes. Under basal conditions the tissues were characterized by a lumen-negative potential difference (PD) of 11 mV and conductance of 5.2 mS/cm2. The short-circuit current (Isc) was 43 microA/cm2 (1.6 mueq.cm-2.h-1). Basal Na+ flows were symmetrical, but net Na+ absorption (1.1 mueq.cm-2.h-1) could be induced by exposure of the luminal surface to amphotericin B (10(-6) M). Bilateral replacement of Na+ reduced Isc by 85%. Replacement of submucosal Na+ or exposure to submucosal furosemide (10(-4) M) reduced net Cl- secretion by 60-70%. Luminal exposure to indomethacin (10(-6) M) induced a 50% decrease in Isc, whereas isoproterenol (10(-6) M) increased Isc by 120%. The properties of the Cl- secretory pathway across fetal dog trachea are consistent with the model proposed for Cl- secretion across adult dog trachea and other Cl- -secreting tissues (e.g., bullfrog cornea and shark rectal gland). The absence of basal Na+ absorption by fetal dog trachea probably reflects limited apical membrane Na+ permeability.

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