Endogenous digitalis-like factors

Schoner, Wilhelm

doi:10.1007/978-3-0348-7150-1_8

Cited by 10 publications

(9 citation statements)

References 129 publications

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“…All cardiotonic steroids tested so far bind with a high affinity to this protein (not shown). The dissociation constant of 1.5 nM ouabain for the high affinity binding site is in the range of the serum concentrations of endogenous ouabain (4,5,15,21,22), and it is also in the range found under therapeutic conditions for digoxin (33). The negative cooperativity of cardiac glycoside binding to the CGBG is astonishing, however.…”

Section: Discussionmentioning

confidence: 89%

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A Specific Binding Protein for Cardiac Glycosides Exists in Bovine Serum

Antolović

Kost

Mohadjerani

et al. 1998

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 89%

“…Consistent with this hypothesis, a number of cardiotonic steroids have recently been isolated from various mammalian tissues and fluids (4,5). Among those are the cardenolides ouabain or its isomer (6 -9), digoxin (10), and the bufadienolides 19-norbufalin (11) and marinobufagenin (12,13).…”

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confidence: 93%

A Specific Binding Protein for Cardiac Glycosides Exists in Bovine Serum

Antolović

Kost

Mohadjerani

et al. 1998

Journal of Biological Chemistry

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“…Plasma of Bufo marinus toad, along with marinobufagenin, contains marinobufagin-3-sulfate, 11␣,19-hydroxymarinobufagin, and marinobufotoxin (conjugate with suberylarginine). 36 Although all of these compounds have demonstrated the ability to inhibit Na ϩ ,K ϩ -ATPase and to displace 3 [H]-ouabain, they have demonstrated different retention times on HPLC columns. 36 The presence of marinobufagenin derivatives in humans could explain in part the fact that several HPLC fractions in our study reacted with marinobufagenin antibody.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3] Endogenous ouabain (or a structurally very similar compound) was the first DLF to be purified from human plasma 4 and bovine brain. 5 However, several studies indicate that mammalian tissues contain other Na ϩ ,K ϩ -ATPase inhibitors that resemble digoxin 6,7 and that sodium pump inhibition observed in hypertension cannot be fully attributed to the action of a ouabain-like compound.…”

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Characterization of a Urinary Bufodienolide Na ⁺ ,K ⁺ -ATPase Inhibitor in Patients After Acute Myocardial Infarction

et al. 1998

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Abstract-Recent evidence suggests the existence of several endogenous Na ϩ ,K ϩ -ATPase inhibitors in mammals. Previously, we have shown that the amphibian Na ϩ ,K ϩ -ATPase inhibitor marinobufagenin (3,5-dihydroxy-14,15-epoxy bufodienolide) acts as a vasoconstrictor in isolated rat and human arteries. Mammalian plasma was shown to contain marinobufagenin-like immunoreactive material, which is responsive to saline volume expansion. The present study describes purification of a bufodienolide, which is similar to marinobufagenin, from the urine of patients after acute myocardial infarction with the use of thin-layer chromatography and reverse-phase high-performance liquid chromatography (HPLC). The purified substance cross-reacted with marinobufagenin antibody, demonstrated maximal UV absorbance at 300 nm characteristic of bufodienolides, and eluted from HPLC columns with the same retention time as marinobufagenin. Mass spectrometry of purified material revealed the presence of a substance indistinguishable from amphibian marinobufagenin and having molecular mass of 400 D. The present studies show that one of the human digitalis-like factors may have a bufodienolide structure and is likely to represent marinobufagenin or its isomer, and they suggest a role for this substance in the pathogenesis of myocardial ischemia. (Hypertension. 1998;31:1097-1103.)

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“…In fact, a material cross-reacting with antibodies against ouabain, digoxin, and digitoxin and inhibiting the sodium pump circulates in increased concentrations in the blood of patients with low renin essential hypertension (1)(2)(3)(4). There has been an intensive search for such substances that has led to the isolation of an ouabain-like inhibitor of the sodium pump from human plasma (5) and an attempt to isolate an isomer of ouabain from bovine hypothalamus (6).…”

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Bovine Adrenals Contain, in Addition to Ouabain, a Second Inhibitor of the Sodium Pump

Schneider¹,

Wray²,

Nimtz³

et al. 1998

Journal of Biological Chemistry

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139

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In the search for endogenous cardiac glycosides, two different inhibitors of the sodium pump have been isolated from bovine adrenals. Inhibitor A with a molecular mass of 600 Da and a UV maximum at 250 nm was purified from 16 kg of bovine adrenals. The pure substance (<1 ng) inhibited the sodium pump of human red blood cells with an affinity similar to that of ouabain, yet it cross-reacted with antibodies against the bufadienolide proscillaridin A but not against the cardenolide ouabain. Inhibitor A was slightly more hydrophilic than ouabain on RP-C 18 high pressure liquid chromatography. Hence, it showed properties similar to the proscillaridin A immunoreactivity (Sich, B., Kirch, U., Tepel, M., Zideck, W., and Schoner, W. (1996) Hypertension 27, 1073-1078) that increased in humans with systolic blood pressure and pulse pressure.Inhibitor B of the sodium pump with a molecular mass of 584 Da was purified 10 6 -fold from 20 kg of bovine adrenals. It cross-reacted with antibodies against ouabain but not with antibodies against proscillaridin A and inhibited the sodium pump of human and rat red blood cells with the same affinity as ouabain. All other properties, such as the retention time in a C 18 -reversed phase chromatography, molecular mass determination by electrospray mass spectrometry and fragmentation pattern, and UV and 1 H NMR spectroscopic data, were identical to ouabain. Hence, sodium pump inhibitor B from bovine adrenals is the cardenolide ouabain.

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Endogenous digitalis-like factors

Cited by 10 publications

References 129 publications

A Specific Binding Protein for Cardiac Glycosides Exists in Bovine Serum

A Specific Binding Protein for Cardiac Glycosides Exists in Bovine Serum

Characterization of a Urinary Bufodienolide Na ⁺ ,K ⁺ -ATPase Inhibitor in Patients After Acute Myocardial Infarction

Bovine Adrenals Contain, in Addition to Ouabain, a Second Inhibitor of the Sodium Pump

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Endogenous digitalis-like factors

Cited by 10 publications

References 129 publications

A Specific Binding Protein for Cardiac Glycosides Exists in Bovine Serum

A Specific Binding Protein for Cardiac Glycosides Exists in Bovine Serum

Characterization of a Urinary Bufodienolide Na + ,K + -ATPase Inhibitor in Patients After Acute Myocardial Infarction

Bovine Adrenals Contain, in Addition to Ouabain, a Second Inhibitor of the Sodium Pump

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Characterization of a Urinary Bufodienolide Na ⁺ ,K ⁺ -ATPase Inhibitor in Patients After Acute Myocardial Infarction