The effects of transport inhibitors on sodium outflux and influx in red blood cells: evidence for exchange diffusion

Dünn, Michael J.

doi:10.1172/jci106398

Cited by 81 publications

(50 citation statements)

References 34 publications

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“…efflux that persisted in the presence of ouabaii from 0.6 to 1.2 ,Aeq/ml cells/h (mean 0.81±0.2 cells/h) for fresh cells suspended in a Na+ Furosemide inhibited this flux by 0.38±0.14 cells/h (n = 10), confirming the studies of Dur Sachs (6,9). Moreover, the absolute inhibition by furosemide was proportional to the magnitu efflux (Fig.…”

Section: Effect Of Furosemide On Active Cation Fluxessupporting

confidence: 82%

“…This discrepancy has been generally attributed to exchange diffusion', and there is some evidence that at least part of the ouabain-insensitive Na+ movements in red cells results from this process (5). In addition, interpretations of studies of the action of furosemide on Nae fluxes maintain that this diuretic drug inhibits Na exchange diffusion in human red cells (6).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A Furosemide-Sensitive Cotransport of Sodium plus Potassium in the Human Red Cell

Wiley¹,

Cooper²

1974

J. Clin. Invest.

236

112

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A B S T R A C T The influxes of Na+ and K+ into the human red cell appear to be interrelated. This relationship was investigated under conditions in which either Na4 or K+ concentration outside the cell was varied or one cation was replaced by Mg2", choline+, or Li'. The effects of furosemide on Na+ and K+ movements were studied in the presence of ouabain.When ouabain was present, Na4 influx was higher with K4 ions externally than with other cations externally. Furosemide inhibited this K+-stimulated Na4 influx, but it had little effect when K+ was absent. Ouabain-insensitive K4 influx was stimulated two-fold by external Nae compared with other cations. Furosemide also inhibited this stimulation, but it had little effect when Mg`4 or choline4 replaced external Nae. Thus it was confirmed that synergism exists between the ouabain-insensitive influxes of Na4 and K4 and it was demostrated that furosemide inhibits this cooperative effect. The ouabaininsensitive influx of both K+ and Na4 showed a hyperbolic "saturating" dependence on the external concentration of the transported cation. Furosemide therefore eliminates a saturable component of influx of each cation.The net uptake of Na+ in the presence of ouabain was stimulated by K4 ions. A similar effect was observed with red cells, in which Li4 replaced nearly all the internal Nae plus K4 ions. In these cells, net Nae uptake was stimulated by external K+, and net K+ uptake was stimulated by external Na+. Furosemide inhibited this mutual stimulation of net cation entries.The inhibitory action of furosemide was not limited to inward flux and net movement of Na4 and K+. Furose-This work has appeared in preliminary form (Clin. Res.

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Section: Effect Of Furosemide On Active Cation Fluxessupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

A Furosemide-Sensitive Cotransport of Sodium plus Potassium in the Human Red Cell

Wiley¹,

Cooper²

1974

J. Clin. Invest.

236

112

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“…Ethacrynic acid interferes with sodium chloride transport in a variety of tissues (24)(25)(26)(27). The inhibitory efaTheophylline indeed inhibits cyclic nucleotide phosphodiesterases, thereby permitting accumulation of intracellular cAMP through basal activity of adenyl cyclase (18,19).…”

Section: Discussionmentioning

confidence: 99%

Effects of Ethacrynic Acid on the Isolated Collecting Tubule

Abramow¹

1974

J. Clin. Invest.

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A B STRACT Effects of the diuretic ethacrynic acid on osmotic water permeability were investigated in the isolated perfused collecting tubule of the rabbit kidney.The base-line water permeability of the collecting tubule was not affected when the drug (10-'M) alone was added to the bathing medium. Vasopressin alone in the bathing medium (2, 5 AU/ml) elicited a significant increase in osmotic water absorption. With vasopressin kept in the bathing medium, the addition of 10-'M ethacrynic acid depressed the hydro-osmotic effect of vasopressin by 50%. This inhibitory effect of low concentrations of ethacrynic acid could be surmounted by high, supramaximal dosage levels of vasopressin.When 10-4M ethacrynic acid was added to the bathing medium before vasopressin, the hydro-osmotic effect of vasopressin and the diuretic in combination was insignificant.Dibutyryl adenosine 3'5'-monophosphate (10-4-10-'M) alone in the bathing medium significantly increased baseline osmotic water flow, mimicing the effect of antidiuretic hormone. When ethacrynic acid was added together with the nucleotide, the permeability remained at the same high level. Theophylline, like the nucleotide and vasopressin, produced a significant hydro-osmotic effect. The magnitude of this responise was not affected by further addition of ethacrynic acid (10-4`\).It was concluded that ethacrynic acid is an antagonist of antidiuretic hormone. The antagonism probably occurs at the level of the receptor site of the hormone on the peritubular membrane. Antagonism to circulating antidiuretic hormone may therefore be one of the factors involved in the loss of renal concentrating ability brought about by ethacrynic acid diuresis.

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“…These results suggest that furosemide acts at a transport site which is activated by either hypertonicity or norepinephrine, and does not interfere with agonist binding or with activation of the adenyl cyclase system. Furosemide's effect on duck red cells resembles its inhibition of ouabain-insensitive cation transport in human red cells (Dunn, 1970(Dunn, , 1973Sachs, 1971;Wiley and Cooper, 1974) which do not respond to catecholamines by significant ion movements or volume response (McManus and Schmidt, unpublished experiments).…”

Section: Rubidium Substitution For Potassiummentioning

confidence: 99%

Ouabain-insensitive salt and water movements in duck red cells. II. Norepinephrine stimulation of sodium plus potassium cotransport.

Schmidt¹,

McManus²

1977

The Journal of General Physiology

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A B S T R A C T Catecholamines induce net salt and water movements in duck redGen. Physiol. 70:59-79. Otherwise, these two systems share a great many similarities. In both cases, net water and salt movements have a marked dependence on external cation concentrations, are sensitive to furosemide and insensitive to ouabain, and allow the substitution of rubidium for external potassium. In the presence of ouabain, but the absence of external potassium (or rubidium), a furosemide-sensitive net extrusion of sodium against a large electrochemical gradient can be demonstrated. When norepinephrine-treated cells are incubated with ouabain and sufficient external sodium, the furosemide-sensitive, unidirectional influxes of both sodium and rubidium are half-maximally saturated at similar rubidium concentrations; with saturating external rubidium, the same fluxes are half-maximal at comparable levels of external sodium. In the absence of sodium, a catecholamine-stimulated, furosemide-sensitive influx of rubidium persists. In the absence of rubidium, a similar but smaller component of sodium influx can be seen. We interpret these results in terms of a cotransport model for sodium plus potassium which is activated by hypertonicity or norepinephrine. When either ion is absent from the incubation medium, the system promotes an exchange-diffusion type of movement of the co-ion into the cells. In the absence of external potassium, net movement of potassium out of the cell leads to a coupled extrusion of sodium against its electrochemical gradient.

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The effects of transport inhibitors on sodium outflux and influx in red blood cells: evidence for exchange diffusion

Cited by 81 publications

References 34 publications

A Furosemide-Sensitive Cotransport of Sodium plus Potassium in the Human Red Cell

A Furosemide-Sensitive Cotransport of Sodium plus Potassium in the Human Red Cell

Effects of Ethacrynic Acid on the Isolated Collecting Tubule

Ouabain-insensitive salt and water movements in duck red cells. II. Norepinephrine stimulation of sodium plus potassium cotransport.

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