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

Schneider, R.; Wray, Victor; Nimtz, Manfred; Lehmann, Wolf D.; Kirch, Ulrike; Antolović, Roberto; Schoner, Wilhelm

doi:10.1074/jbc.273.2.784

Cited by 139 publications

(94 citation statements)

References 21 publications

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“…Ouabain is an endogenous steroid hormone that is present in mammalian tissues; it has been isolated from hypothalamus (39), adrenals (40), and human plasma (41). Evidence indicates that circulating levels of ouabain and ouabain-like factors are elevated during pregnancy and in newborn infants (13,32), thereby suggesting a developmental role for this signaling molecule.…”

Section: Discussionmentioning

confidence: 99%

Na,K-ATPase signal transduction triggers CREB activation and dendritic growth

Desfrère¹,

Karlsson²,

Hiyoshi³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Dendritic growth is pivotal in the neurogenesis of cortical neurons. The sodium pump, or Na,K-ATPase, is an evolutionarily conserved protein that, in addition to its central role in establishing the electrochemical gradient, has recently been reported to function as a receptor and signaling mediator. Although a large body of evidence points toward a dual function for the Na,K-ATPase, few biological implications of this signaling pathway have been described. Here we report that Na,K-ATPase signal transduction triggers dendritic growth as well as a transcriptional program dependent on cAMP response element binding protein (CREB) and cAMP response element (CRE)-mediated gene expression, primarily regulated via Ca 2+ /calmodulin-dependent protein (CaM) kinases. The signaling cascade mediating dendritic arbor growth also involves intracellular Ca 2+ oscillations and sustained phosphorylation of mitogen-activated protein (MAP) kinases. Thus, our results suggest a novel role for the Na,K-ATPase as a modulator of dendritic growth in developing neurons.

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Section: Discussionmentioning

confidence: 99%

Na,K-ATPase signal transduction triggers CREB activation and dendritic growth

Desfrère¹,

Karlsson²,

Hiyoshi³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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“…55 Mass spectrometry and nuclear magnetic resonance studies have indicated that mammalian endogenous ouabain is identical to plant-derived ouabain. 42,43,55 The adrenal cortex and hypothalamus are considered to be the sites of ouabain production in mammals. [55][56][57] Adrenocorticotropic hormone, angiotensin II, vasopressin, and phenylephrine stimulate the release of ouabain from the adrenal cortex in vitro.…”

Section: Subtypes Of Endogenous Cardiotonic Steroids Endogenous Cardementioning

confidence: 99%

Endogenous digitalis: pathophysiologic roles and therapeutic applications

2008

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SUMMARYEndogenous digitalis-like factors, also called cardiotonic steroids, have been thought for nearly half a century to have important roles in health and disease. The endogenous cardiotonic steroids ouabain and marinobufagenin have been identified in humans, and an effector mechanism has been delineated by which these hormones signal through the sodium/potassium-transporting ATPase. These findings have increased interest in this field substantially. Although cardiotonic steroids were first considered important in the regulation of renal sodium transport and arterial pressure, subsequent work has implicated these hormones in the control of cell growth, apoptosis and fibrosis, among other processes. This Review focuses on the role of endogenous cardiotonic steroids in the pathophysiology of essential hypertension, congestive heart failure, end-stage renal disease and pre-eclampsia. We also discuss potential therapeutic strategies that have emerged as a result of the increased understanding of the regulation and actions of cardiotonic steroids.

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“…Recently, Schneider et al (32) isolated another digitalislike substance, a proscillaridin A-like factor, from the bovine adrenal gland. They also report that OLI is present in the same tissue (32). Recently we found that ouabain was isolated from culture supernatant from PC12 cells in the presence of progesterone.…”

Section: Identification Of Endogenous Ouabainmentioning

confidence: 84%

“…Namely, our previous data suggested that the OLI in plasma is exclusively derived from the nervous tissue but not from adrenocortical tissue in rats (13). Schoner and his colleagues recently found a novel sodium pump inhibitor other than ouabain, which was found in the hypothalamus and the adrenal in rats and cows (32,35). Moreover, we (18), Leenen and his colleagues (36), and Yamada et al (37) reported the effect of ouabain on the central nervous system.…”

Section: The Site Of Endogenous Digitalis Productionmentioning

confidence: 92%

Endogenous Digitalislike Factor: An Update

Takahashi

2000

Hypertens Res

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bain is the most promising candidate for a circulating hormone to regulate a number of physiological functions, including hypertension, and that other minor substances may also exist as endogenous digitalislike factors. Most of the symposium contributors submitted papers to this journal. I am going to summarize briefly the research history and current research results on endogenous digitalislike factors (EDLF).(Hypertens Res 2000; 23 Suppl: S1-S5)Key Words: endogenous digitalis, ouabain, digoxin, central nervous system, sympathetic activity Identification of Endogenous DigitalisIt has been more than 40 years since researchers suggested that there exists an endogenous digitalis in mammalian species (1). Hamlyn et al. (2) isolated ouabain from a large amount of human plasma and they claimed that ouabain is the endogenous digitalislike factor (EDLF) that had long been sought. However, other EDLFs such as digoxinlike factors (3), bufodienolide derivatives (4-6), and others have been postulated to be the candidate. So far, because of the significant hypertensinogenic actions of ouabain, it seems to be the most probable candidate to fill the putative roles of EDLFs such as water-electrolytes balance maintenance, vasoconstriction, inotropic action on the heart, and hypertension. Endogenous digoxin may also exist. It has been suggested that digoxinlike immunoreactive substances are closely related with hypertension, heart failure, and renal failure. However, because digoxin administered chronically does not elevate blood pressure in humans, it may not be the cardinal endogenous digitalis for blood pressure regulation. Rather, digoxin is found to decrease blood pressure. This points to endogenous ouabain as a possible novel hypertensinogenic hormone. However, there are still concerns to address before reaching this conclusion. One major concern is that ouabain is present in our diets of plant origin (7) and seems to be incorporated in such organs as the adrenal gland, kidney, and brain. In fact, the distribution of ouabainlike and digoxinlike immunoreactivity of high concentration is restricted in those organs; immunohistohemistry with antidigoxin and anti-ouabain antibody have revealed that the immunoreactivity is restricted in neurons of the hypothalamic (8, 9) and medullary nuclei (10) in the brain. In the adrenals, we have found immunoreactivity in the adrenal medulla (11), but others have claimed to find it in the adrenal cortex (12). In any case, digitalislike immunoreactivity found not only in the brain and but also in the adrenals could be of plant origin. However, because plasma concentrations and hypothalamic content of ouabainlike immunoreactivity are markedly reduced by intracerebroventricular (ICV) injections of 6-hydroxydopamine in comparison to amounts in sham-operated rats (13), the existence of endogenously formed ouabain, at least in the brain, is highly probable. Furthermore, some hyperten-

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

Cited by 139 publications

References 21 publications

Na,K-ATPase signal transduction triggers CREB activation and dendritic growth

Na,K-ATPase signal transduction triggers CREB activation and dendritic growth

Endogenous digitalis: pathophysiologic roles and therapeutic applications

Endogenous Digitalislike Factor: An Update

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