Binding sites related to ouabain-induced stimulation or inhibition of the sodium pump

Godfraind, Théophile; Ghysel-Burton, J

doi:10.1038/265165a0

Cited by 99 publications

(32 citation statements)

References 12 publications

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“…1973;Cohen, Daut & Noble. 1976;Godfraind & Ghysel-Burton, 1977). Previous observations with 42K (Godfraind & Lesne.…”

Section: Discussionmentioning

confidence: 86%

“…This 3-h incubation time was found to be required in order to observe the ouabain equilibrium effect (Godfraind & Ghysel-Burton, 1977). The action of ouabain on Na and K contents was qualitatively different according to the ouabain concentration employed.…”

Section: Resultsmentioning

confidence: 99%

“…Both bindings were sensitive to changes in K. which affected the apparent affinity of both groups of sites for ouabain (Godfraind & Ghysel-Burton, 1977 (Table 2).…”

Section: Thie Binding Of Ouabainmentioning

confidence: 99%

“…More recently, it has been shown in electrically driven left atria of guinea-pig, that the stimulation and the inhibition of the sodium pump were related to high-and low-affinity ouabain binding sites. Evidence has been given that these two bindings were to the sodium pump (Godfraind & Ghysel-Burton, 1977).…”

Section: Introductionmentioning

confidence: 99%

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Stimulation and Inhibition of the Sodium Pump by Cardioactive Steroids in Relation to Their Binding Sites and Their Inotropic Effect on Guinea‐pig Isolated Atria

Ghysel-Burton

Godfraind

1979

British J Pharmacology

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I The actions of ouabain, ouabagenin and dihydroouabain on the contractility and on the ionic content have been investigated in left guinea-pig atria stimulated at 3.3 Hz. The specific binding of ouabain and its displacement by the other cardenolides have been determined. 2 The action of either ouabain or ouabagenin on Na and K content was qualitatively different according to the concentration employed. Low doses evoked a reduction of Nai whereas high doses produced an increase. Dihydroouabain evoked only a Nai gain.3 The increase of KCI concentration from 2.7 to 12 mm decreased Na, in untreated atria and displaced ouabain dose-effect curves to the right.4 ED50 values for the positive inotropic effect were lower than ED50 values for the inhibition of the pump and were not similarly affected by an increase in KCI concentration. 5 The specific binding of ouabain occurred at high and low affinity sites, related to Na pump stimulation and inhibition respectively. 6 The increase in KCI reduced the affinity of the two groups of sites for ouabain and increased the capacity of the high-affinity sites whereas the capacity of the other sites remained unchanged. 7 The results confirm the existence of two specific binding sites for ouabain in guinea-pig heart and suggest that the inhibition of the Na pump is not the only mechanism responsible for the positive inotropic effect of cardiac glycosides.

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“…1973;Cohen, Daut & Noble. 1976;Godfraind & Ghysel-Burton, 1977). Previous observations with 42K (Godfraind & Lesne.…”

Section: Discussionmentioning

confidence: 86%

Section: Resultsmentioning

confidence: 99%

“…Both bindings were sensitive to changes in K. which affected the apparent affinity of both groups of sites for ouabain (Godfraind & Ghysel-Burton, 1977 (Table 2).…”

Section: Thie Binding Of Ouabainmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Stimulation and Inhibition of the Sodium Pump by Cardioactive Steroids in Relation to Their Binding Sites and Their Inotropic Effect on Guinea‐pig Isolated Atria

Ghysel-Burton

Godfraind

1979

British J Pharmacology

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“…However, this concentration was chosen because it did not alter the baseline tension and the contractile responses to acetylcholine, and because a previous study showed that K + loss and Na + accumulation were produced by 50 nM ouabain in other tissues [24]. To further support the notion that Na + -K + -ATPase is involved, ouabain-sensitive 86 Rb uptake by tracheal tissues, an index of Na + -K + -ATPase activity [18], was measured, and it was found that incubation of tissues with TJ-17 and TJ-23 increased ouabain-sensitive 86 Rb uptake in a concentration-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of airway smooth muscle tone by Chinese herbal medicines

Tagaya¹,

Tamaoki²,

Kawatani³

et al. 2000

Eur Respir J

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The aim of the present study was to elucidate whether Chinese traditional herbal drugs, Gorei-San (TJ-17) and Toki-Shakuyaku-San (TJ-23), affect airway smooth muscle tone and, if so, to determine what the mechanism of action is.Rabbit tracheal segments were isolated and the contractile responses to electrical field stimulation and acetylcholine were measured before and after the application of TJ-17 or TJ-23 under isometric conditions in vitro. Ouabain-sensitive rubidium-86 ( 86 Rb) uptake by tissues in response to each drug was also measured.Each herbal medicine attenuated the contractile responses to electrical field stimulation and acetylcholine in a concentration-dependent manner, the maximal inhibition of acetylcholine-induced contraction being 37.5 4.9% for TJ-17 and 42.4 5.3% for TJ-23 (p<0.05 for each). These effects were not altered by mechanical removal of the epithelium, indomethacin, the nitric oxide synthase inhibitor N G -nitro-L-arginine methyl ester, the cyclic adenosine monophosphate (cAMP)-dependent protein kinase inhibitor adenosine 3'5'-cyclic monophosphorothiioate (Rp-cAMPS), the cyclic guanosine monophosphate (cGMP)-dependent protein kinase inhibitor KT5823, or the calcium (Ca 2+ )-activated potassium (K + ) channel inhibitor charybdotoxin, but were greatly inhibited in the presence of the sodium (Na + )-K + adenosine triphosphatase (ATPase) inhibitor ouabain. Incubation of tissues with TJ-17 and TJ-23 dose dependently increased ouabain-sensitive 86 Rb uptake.The results of the study suggest that both Gorei-San and Toki-Shakuyaku-San reduce airway smooth muscle tone via a postjunctional mechanism probably through stimulation of the sodium pump and the subsequent hyperpolarization/repolarization of the cell membrane. These effects may contribute to the antiasthmatic properties of these herbal medicines.

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Erythrocyte sodium pump stimulation by ouabain and an endogenous ouabain‐like factor

Balzan

D'Urso²,

Nicolini

et al. 2006

Cell Biochemistry & Function

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Cardiac glycosides inhibit the sodium pump. However, some studies suggest that nanomolar ouabain concentrations can stimulate the activity of the sodium pump. In this study, using the Na(+)/K(+)-ATPase of human erythrocytes, we compared the effect of digoxin, ouabain and an ouabain like-factor (OLF), on (86)Rb uptake. Ouabain concentrations below 10(-9) M significantly stimulate Rb(+) uptake, and the maximal increase above base-line values is 18 +/- 5% at 10(-10) M ouabain. No stimulation is observed in the same conditions by digoxin. OLF behaved like ouabain, producing an activation of Rb(+) flux at concentrations lower than 10(-9) M ouabain equivalents (14 +/- 3% at 10(-10) M). Western blot analysis revealed the presence of both alpha(1) and alpha(3) pump isoforms in human erythrocytes. Our data confirm the analogies between OLF and ouabain and suggest that Na(+)/K(+)-ATPase activation may be related to the alpha(3) isoform. In addition, we investigated whether ouabain at different concentrations was effective in altering the intracellular calcium concentration of erythrocytes. We found that ouabain at concentration lower than 10(-9) M did not affect this homeostasis.

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Binding sites related to ouabain-induced stimulation or inhibition of the sodium pump

Cited by 99 publications

References 12 publications

Stimulation and Inhibition of the Sodium Pump by Cardioactive Steroids in Relation to Their Binding Sites and Their Inotropic Effect on Guinea‐pig Isolated Atria

Stimulation and Inhibition of the Sodium Pump by Cardioactive Steroids in Relation to Their Binding Sites and Their Inotropic Effect on Guinea‐pig Isolated Atria

Inhibition of airway smooth muscle tone by Chinese herbal medicines

Erythrocyte sodium pump stimulation by ouabain and an endogenous ouabain‐like factor

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