Binding of the cardiac glycoside ouabain to intact cells

Baker, P. F.; Willis, John S.

doi:10.1113/jphysiol.1972.sp009904

Cited by 199 publications

(144 citation statements)

References 21 publications

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“…The binding of cardiac glycosides to their putative receptor, Na+, K+-ATPase, has been studied in detail in several different tissues and species by a number of workers (for references see Schwartz et al, 1975). Glycoside binding to human red cells (see Table 1 for references) has previously been shown to possess the following characteristics: With respect to our figures for maximum binding there was good agreement with the data of Ellory & Keynes (1969), Hoffman (1969, Erdmann & Hasse (1975) and Baker & Willis (1972). Gardner and his co-workers (Gardner & Conlon, 1972;Gardner, Kiino, Swartz & Butler, 1973) binding by unlabelled digoxin are of similar magnitude (9.4 x 10-9M and 9.1 x 10-9M respectively, Table 1).…”

Section: Resultssupporting

confidence: 75%

The characteristics of the binding of 12‐alpha‐[3H]‐digoxin to the membranes of intact human erythrocytes: relevance to digoxin therapy.

Ford¹,

Aronson²,

Grahame‐Smith³

et al. 1979

Brit J Clinical Pharma

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1 The characteristics of the binding of 12‐alpha‐[3H]‐digoxin to the membranes of intact human erythrocytes are described. 2 Only one class of binding site can be demonstrated. Binding is time‐ and temperature‐ dependent, saturable and slowly reversible; it is inhibited by other cardiac glycosides and by potassium. 3 Pre‐incubation with unlabelled digoxin reduces the subsequent binding of 12‐alpha‐[3H]‐digoxin in stoichiometric fashion. 4 The possible application of the measurement of the binding of 12‐alpha‐[3H]‐digoxin to the study of biochemical pharmacological events occurring during digoxin therapy is discussed.

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Section: Resultssupporting

confidence: 75%

The characteristics of the binding of 12‐alpha‐[3H]‐digoxin to the membranes of intact human erythrocytes: relevance to digoxin therapy.

Ford¹,

Aronson²,

Grahame‐Smith³

et al. 1979

Brit J Clinical Pharma

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“…Determination of the number of Na pumps in fragmented membrane preparations thus requires optimum conditions for ouabain binding and evidence of saturation. Also in intact cells, the binding of ouabain to the outer surface of the plasma membrane may proceed for several hours before equilibrium is reached (Baker & Willis, 1972;Clausen & Hansen, 1974;Joiner & Lauf, 1975;Bodemann &Hoffmann, 1976).…”

Section: Introductionmentioning

confidence: 99%

Active Na—K transport and the rate of ouabain binding. The effect of insulin and other stimuli on skeletal muscle and adipocytes

Clausen¹,

Hansen²

1977

The Journal of Physiology

137

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SUMMARY1. The effect of stimulation or inhibition of active Na-K transport on [3H]ouabain binding has been investigated in isolated soleus muscles and adipocytes.2. In rat soleus muscle, the ouabain-sensitive component of 42K influx was stimulated by insulin (100 m-u/ml.), adrenaline (6 x 106 M), and by pre-incubation with veratrine (10-5 M) or in a K-free buffer. In all of these instances, the rate of ouabain binding was increased by 41-113%. Conversely, pre-treatment with tetracaine (0.2 mM) decreased the 42K-influx and diminished the rate of [3H]ouabain binding by 36 %.3. Neither insulin, adrenaline or tetracaine produced any detectable change in the total number of ouabain-binding sites (as measured under equilibrium conditions) in rat soleus muscle.4. In mouse and guinea-pig soleus muscle and in fat cells isolated from rats, insulin also increased the rate of [3H]ouabain binding without producing any significant change in the total number of ouabain-binding sites.5. Both in soleus muscle and the epididymal fat pad of the rat, there was a linear correlation between 42K influx and the initial rate of [3H]-ouabain binding.6. It is concluded that the rate of ouabain binding is determined significantly by the rate of active Na-K transport, but within the time intervals studied (4-6 hr) stimulation or inhibition of the Na pump does not lead to any appreciable change in the total number of Na pumps. It seems unlikely that the stimulation of active Na-K transport by insulin or adrenaline is due to unmasking or de novo synthesis of Na pumps.

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“…In various preparations the binding of cardiac glycosides was found to be proportional to the Na+ concentration (Baker & Willis, 1972;Gardner & Conlon, 1972;Lindenmayer et al, 1973;Erdmann & Schoner, 1973;Inagaki etal., 1974;Hobbs & Dunham, 1978;Furukawa et al, 1980). However, the reduction of ouabain receptor affinity cannot be the sole mechanism by which Na+ withdrawal reduces the inotropic effect of cardiac glycosides.…”

Section: Discussionmentioning

confidence: 99%

Potassium changes the relationship between receptor occupancy and the inotropic effect of cardiac glycosides in guinea‐pig myocardium

Bachmaier¹,

Ebner²,

Reiter³

1985

British J Pharmacology

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I K+ (2.4-15.6mmoll-') antagonized the positive inotropic effect of dihydro-ouabain. The concentration-effect curves became steeper with the shift to higher concentrations of the glycoside. At 1.2 mmol 1-Ca2+, an increase in K+ from 2.4 to 12 mmol 1-P' required tenfold higher concentrations of dihydro-ouabain to produce equal inotropic effects. This factor was reduced to four at 3.2 mmol I-, Ca2+ . The same change in K+ concentration, at 1.2 mmol 1-' Ca2+, diminished the inotropic effect of ouabain on rested-state contractions by a factor of six. 2 The positive inotropic effect of Ca2+ was also antagonized by K+ (1.2-12 mmol 1-'). Reduction of Na+ from 140 to 70 mmol 1-' abolished the antagonistic action of K+ (1.2-8.0 mmol 1-'). Moreover the inotropic effect of Ca2" was enhanced.3 Reduction of Na+, from 140 to 70 mmol -', antagonized the positive inotropic effect of dihydroouabain more at low (2.4 mmol l') than at high (8.0 mmol I') K+. Accordingly, the extent of the dihydro-ouabain-K+ antagonism was reduced. 4 When the K+ concentration was increased from 2.4 to 12mmoll-', [3H]-ouabain binding was reduced by a factor of three. This is less than the reduction in the inotropic effectiveness of ouabain or dihydro-ouabain. 5 Reduction of stimulation frequency from 1 to 0.1215 Hz did not significantly alter the antagonistic effect of K+. Diminution of Vmax of the action potential was observed only at K+ concentrations greater than 5.9 mmol 1-, whereas the resting membrane potential was continuously depolarized over the entire range of K+ concentrations. 6 The results support the view that the reduction in receptor affinity cannot be the sole cause of the antagonism between the glycoside and K+. Impairment of passive Na+ influx during diastole, due to the K+-dependent depolarization of the resting membrane potential, contributed to about one half of the glycoside-K+ antagonism.

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Binding of the cardiac glycoside ouabain to intact cells

Cited by 199 publications

References 21 publications

The characteristics of the binding of 12‐alpha‐[3H]‐digoxin to the membranes of intact human erythrocytes: relevance to digoxin therapy.

The characteristics of the binding of 12‐alpha‐[3H]‐digoxin to the membranes of intact human erythrocytes: relevance to digoxin therapy.

Active Na—K transport and the rate of ouabain binding. The effect of insulin and other stimuli on skeletal muscle and adipocytes

Potassium changes the relationship between receptor occupancy and the inotropic effect of cardiac glycosides in guinea‐pig myocardium

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