Endogenous Cardiac Glycosides

Kelly, Ralph A.; Smith, Thomas W.

doi:10.1016/s1054-3589(08)60434-2

Cited by 13 publications

(6 citation statements)

References 85 publications

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“…Differences in ouabain sensitivity of the Na,K-ATPase isozymes have been proposed to have a role in the regulation of Na,K-ATPase activity (reviewed in Blanco and Mercer 1998). This is supported by the identification of endogenous ouabain-like compounds in mammalian tissues (Blaustein 1993(Blaustein ,1994Kelly and Smith 1994;Doris 1996). Interestingly, endogenous digoxin-like Figure 6 Ouabain inhibition of Na,K-ATPase from normal and Egr4-deficient mice.…”

Section: Discussionmentioning

confidence: 99%

The α4 Isoform of the Na,K-ATPase Is Expressed in the Germ Cells of the Testes

Blanco

Sánchez

Melton

et al. 2000

J Histochem Cytochem.

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In addition to the three isoforms of the catalytic subunit of the Na,K-ATPase originally identified (α1, α2, and α3), a fourth α polypeptide (α4) has recently been found in mammalian cells. This novel α-subunit of the Na,K-ATPase is selectively expressed in male gonadal tissues. In the testes, α4 is functionally active and comprises approximately half of the Na,K-ATPase activity of the organ. At present, the pattern of expression of the α4 polypeptide within the cells of the male gonad is unknown. By in situ hybridization, immunocytochemistry, and the ouabain inhibition profile of Na,K-ATPase activity, we show that the α4-subunit is expressed in the germ cells of rat testes. The highest amounts of the isoform are found in spermatozoa, where it constitutes two thirds of the Na,K-ATPase activity of the gametes. The other Na pump present in the cells is the ubiquitously expressed α1 polypeptide. The characteristic localization of α4 in the gonad is further supported by the drastic reduction of the polypeptide in mice that are infertile as a consequence of arrest in maturation of the germ cells. In addition, GC-1spg cells, a murine cell line derived from testis spermatogonia, also contain the Na,K-ATPase α4 polypeptide. However, the level of expression of the isoform in these cells is much lower than in the spermatozoa, a fact that may depend on the limited ability of the GC-1spg cells to differentiate in vitro. The particular expression of the Na,K-ATPase α4 isoform we encounter and the specific enzymatic properties of the polypeptide suggests its importance for ionic homeostasis of the germ cells of the testes. (J Histochem Cytochem 48:1023–1032, 2000)

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Section: Discussionmentioning

confidence: 99%

The α4 Isoform of the Na,K-ATPase Is Expressed in the Germ Cells of the Testes

Blanco

Sánchez

Melton

et al. 2000

J Histochem Cytochem.

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“…However, some authors are uncertain about the existence of such an inhibitor and its role in hypertension [101], indicating that it is possible that the digitalis receptor is only an enzyme feature needed for its activity as cationic pump. Moreover, it is argued that isolated EDLF amounts are so small that they do not seem to be important for playing a physiological role, even when it can be considered the possibility of a located release or a selective affinity for one of Na + ,K + -ATPase isoenzymes.…”

Section: Endogenous Digitalis-like Factorsmentioning

confidence: 99%

A Short Review on Cardiotonic Steroids and Their Aminoguanidine Analogues

2000

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“…The varying interpretations in the conflicting reports on this matter have mainly been due to differences of methodology and the appearance of endogenous and exogenous digoxin-like immunoreactive substances. Those have been found in blood, urine and other body fluids (Kelly & Smith 1994): They cross-react with anti-digoxin antibodies and erroneously increases S-digoxin concentrations, thereby complicating the interpretation thereof (Dasgupta 2002). Exogenous digoxin-like immunoreactive substances can be found in serum after therapy with e.g.…”

Section: Signs Of Digoxin Intoxication In Newbornsmentioning

confidence: 99%

Gastrointestinal Symptoms as an Important Sign in Premature Newborns with Severely Increased S‐Digoxin

Nybo

Damkier

2005

Basic Clin Pharma Tox

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Abstract:The aim is to emphasize the importance of extracardiac symptoms of digoxin intoxication in newborns. The most common intoxication symptoms in adults are of cardiac origin, but due to altered symptomatology, digoxin overdose in infants are not always discovered on symptomatic basis. In preterm infants, this is even more pronounced due to diminished digoxin sensitivity. Also, tissue distribution is altered in newborns, which, combined with the need for higher doses in newborns to obtain clinical effect, underscores the need for the utmost care, when newborns receive digoxin treatment to avoid intoxication. We report a case of severe digoxin intoxication in a preterm newborn infant, leading to distinct gastrointestinal symptoms, but only minor cardiac affection. The literature concerning digoxin intoxication and digoxin measurement is reviewed to elucidate the case report. In conclusion, alertness should be drawn to extracardiac symptoms of digoxin intoxication, especially in newborns, and P-Potassium can serve as a predictor and thereby strengthen any given suspicion. Therapeutic drug monitoring should be performed, as soon as digoxin overdose due to the abovementioned signs is suspected in spite of vague cardiac symptoms.

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Endogenous Cardiac Glycosides

Cited by 13 publications

References 85 publications

The α4 Isoform of the Na,K-ATPase Is Expressed in the Germ Cells of the Testes

The α4 Isoform of the Na,K-ATPase Is Expressed in the Germ Cells of the Testes

A Short Review on Cardiotonic Steroids and Their Aminoguanidine Analogues

Gastrointestinal Symptoms as an Important Sign in Premature Newborns with Severely Increased S‐Digoxin

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