Digitalis-like factors in plasma of healthy human adults

Vasdev, Sudesh; Longerich, L; Johnson, E; Brent, David A.; Gault, M. H.

doi:10.1007/978-3-662-11292-2_21

Cited by 4 publications

(5 citation statements)

References 17 publications

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“…The increase in the crossreactivity of the N fraction after hydrolysis was statistically significant. Among DLIFs in the literature, fatty acids, such as linoleic and oleic acids (Tamura et al, 1985), and dehydroepiandrosterone sulphate (Vasdev et al, 1985) should be fractionated in the S fraction in the present experiments, and steroid hormones such as estrogens and lignans such as enterolactone and enterodiol (Fagoo et al, 1985) should be present in the W fraction. The observed reactivity of both fractions can be satisfactorily explained by the presence of these known candidates.…”

Section: Discussionmentioning

confidence: 98%

“…Quite recently, another factor with stronger digoxinlike activity was indicated as possibly causing an increase in the biofluids of animals with volume expansion (Hernandez, 1987;Rauch and Buckalew, 1988;Goto et al, 1988bTamura et al, 1988). Also, mammalian lignans (Vasdev et al, 1985;Fagoo et al, 1985) and physiological steroids such as progesterone or cortisol (Longerich et al, 1988) may possibly be DLIFs. It thus appears quite likely that endogenous factors possessing digoxin-like activities are distributed among various molecular species and are not limited to the compounds mentioned above.…”

Section: Introductionmentioning

confidence: 94%

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pH‐dependent colum fractionation for characterization of endogenous digoxin‐like immunoractive factors in pregnant urine

Homma

Hirano

Oka

1991

Biomedical Chromatography

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Samples of pregnant urine were treated with three diatomaceous earth columns to fractionate organic solvent-soluble components. The first column was pre-injected with the urine sample. The second and the third columns were pre-injected with sodium bicarbonate and sodium hydroxide solutions, respectively; these played an important role in capturing acidic components in the urine extract from the first column. Neutral components could be eluted out from the columns with the organic solvent, while the basic components were retained in the first column. Once strongly and weakly acidic components were captured on the alkaline columns, they were separately treated with an acidic mobile phase and recovered. The digoxin-like activities of each fraction were examined for cross-reactivity to antidigoxin antibody and inhibitory effects on dog kidney Na+, K(+)-ATPase. Both types of reactivity were found in all three fractions and decreased in the following order: strongly acidic, neutral and weakly acidic. The neutral fraction of pregnant urine showed significantly greater cross-reactivity than that of the non-pregnant urine. Following hydrolysis of the pregnant urine with beta-D-glucuronidase, the cross-reactivity of the neutral fraction increased significantly. High performance liquid chromatographic analysis showed that several components in the neutral fraction had apparently increased after the hydrolysis, showing the possible presence of unknown digoxin-like components in the pregnant urine.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 94%

pH‐dependent colum fractionation for characterization of endogenous digoxin‐like immunoractive factors in pregnant urine

Homma

Hirano

Oka

1991

Biomedical Chromatography

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“…However, in many of these studies, it has not been possible to determine the structure of the inhibitors or to clarify the nature of their interaction with Na+,K+-ATPase because many of these studies were mainly focused on obtaining evidence for the existence of the inhibitors. Only a limited number of studies including our previous studies have revealed that several compounds such as unsaturated fatty acids (Bidard et al, 1984;Tamura et al, 1985; Kelly et al, 1986), lysophosphatidylcholines (Bidard et al, 1984;Kelly et al, 1986;Tamura et al, 1987a,b), dihydroxyeicosatrienoic acid (Schwartzman et al, 1985), dopamine , dehydroepiandrosterone sulfate (Vasdev et al, 1985), lignan (Fagoo et al, 1986), and ascorbic acid (Ng et al, 1985) are endogenous substances with the inhibitory activity. However, they do not fulfill all of the criteria for an endogenous Na+,K+-ATPase inhibitor which should (i) be of low molecular weight, (ii) inhibits Na+,K+-ATPase, (iii) displaces [3H]ouabain bound to the enzyme, (iv) inhibits Na+,K+ pump activity, (v) cross-reacts with anti-digoxin antibody, and (vi) does not interfere with other ATPase.…”

Section: Discussionmentioning

confidence: 99%

Isolation and characterization of a specific endogenous sodium-potassium ATPase inhibitor from bovine adrenal

Tamura¹,

Lam²,

Inagami³

et al. 1988

Biochemistry

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In order to identify a specific endogenous Na+,K+-ATPase inhibitor which could possibly be related to salt-dependent hypertension, we looked for substances in the methanol extract of bovine whole adrenal which show all of the following properties: (i) inhibitory activity for Na+,K+-ATPase; (ii) competitive displacing activity against [3H]ouabain binding to the enzyme; (iii) inhibitory activity for 86Rb uptake into intact human erythrocytes; and (iv) cross-reactivity with sheep anti-digoxin-specific antibody. After stepwise fractionation of the methanol extract of bovine adrenal glands by chromatography on a C18 open column, a 0-15% acetonitrile fraction was fractionated by high-performance liquid chromatography on a Zorbax octadecylsilane column. One of the most active fractions in 0-15% acetonitrile was found to exhibit all of the four types of the activities. It was soluble in water and was distinct from various substances which have been known to inhibit Na+,K+-ATPase such as unsaturated free fatty acids, lysophosphatidylcholines, vanadate, dihydroxyeicosatrienoic acid, dehydroepiandrosterone sulfate, dopamine, lignan, ascorbic acid, etc. This substance was further purified by using an additional five steps of high-performance liquid chromatography with five different types of columns. Molecular mass was estimated as below 350 by fast atom bombardment mass spectroscopy and ultrafiltration. Heat treatment at 250 degrees C for 2 h and acid treatment with 6 N HCl at 115 degrees C for 21 h almost completely destroyed the inhibitory activity of the purified substance for Na+ pump activity. Additionally, alkaline treatment with 0.2 N NaOH at 23 degrees C for 2 h destroyed approximately 70% of the inhibitory activity, whereas boiling for 10 min and various enzyme digestion did not destroy the activity. The dose dependency for the four types of the activities for this substance paralleled those of ouabain, spanning 2 orders of magnitude in concentration range. The inhibitory potencies of the purified substance for Na+,K+-ATPase, Na+ pump, and ouabain binding activities were diminished with increasing K+ concentration, exhibiting a characteristic typical of cardiac glycosides. This substance had no effect on the Ca2+-ATPase activity or the Ca2+ loading rate into the vesicle prepared from skeletal muscle sarcoplasmic reticulum. These results strongly suggest that this water-soluble nonpeptidic Na+,K+-ATPase inhibitor may be a specific endogenous regulator for the ATPase.

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“…First, it has been reported that steroid hormones suppress glucuronyl transferase activity (25,26). Recent studies have suggested that DLIF may be of steroidal nature (13)(14)(15), and that its origin is the adrenal gland (16). If so, DLIF might also inhibit the activity of glucuronyl transferase, and impede bile flow and excretion.…”

Section: Digoxin-like Factor In Neonates 367mentioning

confidence: 99%

“…The nature and source of DLIF is still unclear, but recently several physical and chemical characteristics have been described (12,13). DLIF may be of steroidal nature (14,15) and the adrenal gland its source (16). Several investigators have demonstrated that DLIF has natriuretic properties (6,17), raising the possibility that it plays a physiologic role in water and sodium homeostasis.…”

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confidence: 99%

Endogenous Digoxin-Like Factor in Neonates: Effect of Age and Relation to Serum Bilirubin Levels

Wolach¹,

Carmi²,

Shilo³

et al. 1989

Acta Paediatrica

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Endogenous digoxin-like immunoreactive factor(s) (DLIF) have been found in serum and urine of newborn infants, including those born prematurely. We assessed the effect of age on serum levels of DLIF in 73 samples obtained from 66 healthy full term newborn infants at birth and during the first two months of life. DLIF concentrations were highest at birth and fell progressively with age. In cord blood, DLIF levels were 0.73 +/- 0.35 ng/ml (mean +/- SD). DLIF concentrations were 0.45 +/- 0.11 ng/ml on day 1, 0.26 +/- 0.08 ng/ml on day 3, 0.19 +/- 0.07 ng/ml on day 5, 0.17 +/- 0.09 ng/ml on day 11, 0.11 +/- 0.02 ng/ml on days 15-30, and not detectable after 45 days of life. We also studied the relation between serum levels of DLIF and bilirubin in 23 jaundiced newborns between 3-5 days of life. We found a highly significant positive correlation between serum bilirubin concentrations and DLIF. These findings support the assumption that DLIF plays a role in impeding bilirubin excretion in the neonatal period, perhaps by inhibiting the activity of (Na-K)ATPase.

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Digitalis-like factors in plasma of healthy human adults

Cited by 4 publications

References 17 publications

pH‐dependent colum fractionation for characterization of endogenous digoxin‐like immunoractive factors in pregnant urine

pH‐dependent colum fractionation for characterization of endogenous digoxin‐like immunoractive factors in pregnant urine

Isolation and characterization of a specific endogenous sodium-potassium ATPase inhibitor from bovine adrenal

Endogenous Digoxin-Like Factor in Neonates: Effect of Age and Relation to Serum Bilirubin Levels

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