Bovine adrenocortical cells in culture synthesize an ouabain-like compound

Perrin, Anne; Brasmes, B; Chambaz, E.M.; Defaye, G.

doi:10.1016/s0303-7207(96)03964-0

Cited by 62 publications

(42 citation statements)

References 30 publications

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“…Whether bovine adrenals secrete ouabain or its isomer into the plasma will be of considerable interest. From the finding that ouabain-immunoreactive material is released from bovine adrenal cortical cells in tissue culture by ACTH and angiotensin II (10,11) and that the released amount is higher after incubation of the cells with pregnenolone and progesterone, one may conclude that ouabain is synthesized there from these precursors (26) and is stored there. Eventually, this may be valid also for other tissues, since the hypothalamus and adrenal glands of rat and cow are the richest sources of ouabain and proscillaridin A immunoreactivities (27).…”

Section: Discussionmentioning

confidence: 99%

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

Schneider¹,

Wray²,

Nimtz³

et al. 1998

Journal of Biological Chemistry

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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Section: Discussionmentioning

confidence: 99%

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

Schneider¹,

Wray²,

Nimtz³

et al. 1998

Journal of Biological Chemistry

139

View full text Add to dashboard Cite

show abstract

“…The identification and characterization of the circulating Na C /K C ATPase antagonist remained elusive for a long time. After painstaking research spanning three decades, two groups independently identified the circulating factor(s) as substances similar to plant-derived ouabain and digoxin that are synthesized in the mammalian adrenal glands (Hamlyn et al 1982, 1991, Craver & Valdes 1983, Graves et al 1983, Valdes 1985a,b,c, Valdes et al 1985, Skogen et al 1987, Lackner et al 1988, Siegfried & Valdes 1988, Shaikh et al 1991, Qazzaz & Valdes 1996, Qazzaz et al 1996a,b, 2000, Ferrandi et al 1997, Jortani & Valdes 1997, Perrin et al 1997, Grider et al 1999, Manunta et al 2001a,b, Pierdomenico et al 2001, el-Masri et al 2002, El-Mallakh et al 2007). Bagrov and colleagues identified the presence of endogenous bufadienolides, marinobufagenin, and telocinobufagin, in plasma of rats with renal failure, diabetes, and preeclampsia, and in plasma from patients with congestive heart failure and renal failure (Bagrov et al 1996, 2005, 2005a,b, 2010a,b, 2012, Gonick et al 1998, Lopatin et al 1999 Effects of low nanomolar to picomolar concentrations of ouabain on Na…”

Section: Endogenous Cardiotonic Steroids In Cardiac and Renal Diseasesmentioning

confidence: 99%

Advances in understanding the role of cardiac glycosides in control of sodium transport in renal tubules

Khundmiri¹

2014

Journal of Endocrinology

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Cardiotonic steroids have been used for the past 200 years in the treatment of congestive heart failure. As specific inhibitors of membrane-bound Na C /K C ATPase, they enhance cardiac contractility through increasing myocardial cell calcium concentration in response to the resulting increase in intracellular Na concentration. The half-minimal concentrations of cardiotonic steroids required to inhibit Na C /K C ATPase range from nanomolar to micromolar concentrations. In contrast, the circulating levels of cardiotonic steroids under physiological conditions are in the low picomolar concentration range in healthy subjects, increasing to high picomolar levels under pathophysiological conditions including chronic kidney disease and heart failure. Little is known about the physiological function of low picomolar concentrations of cardiotonic steroids. Recent studies have indicated that physiological concentrations of cardiotonic steroids acutely stimulate the activity of Na C /K C ATPase and activate an intracellular signaling pathway that regulates a variety of intracellular functions including cell growth and hypertrophy. The effects of circulating cardiotonic steroids on renal salt handling and total body sodium homeostasis are unknown. This review will focus on the role of low picomolar concentrations of cardiotonic steroids in renal Na C /K C ATPase activity, cell signaling, and blood pressure regulation.

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“…The biosynthesis of EO utilizes cholesterol and progesterone as precursors (44,45,61,87,92) and follows the same initial steps as in plants and in aldosterone production. The EO biosynthetic pathway diverges from the aldosterone pathway either 1) at corticosterone, in which case there is an 11␤ hydroxyl, forming a stereoisomer of ouabain, as suggested by some mass spectrometry and NMR data (44,45) or 2) at 11-deoxycorticosterone, which allows an 11␣ hydroxyl, as in ouabain itself.…”

Section: Endogenous Ouabain and Other Endogenous Cardiotonic Steroidsmentioning

confidence: 99%

How does salt retention raise blood pressure?

Blaustein¹,

Zhang²,

Ling³

et al. 2006

American Journal of Physiology-Regulatory, Integrative and Comp

129

121

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A critical question in hypertension research is: How is long-term blood pressure controlled? Excessive NaCl ingestion or NaCl retention by the kidneys and the consequent tendency toward plasma volume expansion lead to hypertension. Nevertheless, the precise mechanisms linking salt to high blood pressure are unresolved. The discovery of endogenous ouabain, an adrenocortical hormone, provided an important clue. Ouabain, a selective Na ϩ pump inhibitor, has cardiotonic and vasotonic effects. Plasma endogenous ouabain levels are significantly elevated in Ϸ40% of patients with essential hypertension and in animals with several forms of salt-dependent hypertension. Also, prolonged ouabain administration induces hypertension in rodents. Mice with mutant Na ϩ pumps or Na/Ca exchangers (NCX) and studies with a ouabain antagonist and an NCX blocker are revealing the missing molecular mechanisms. These data demonstrate that ␣ 2 Na ϩ pumps and NCX1 participate in long-term regulation of vascular tone and blood pressure. Pharmacological agents or mutations in the ␣ 2 Na ϩ pump that interfere with the action of ouabain on the pump, and reduced NCX1 expression or agents that block NCX all impede the development of salt-dependent or ouabain-induced hypertension. Conversely, nanomolar ouabain, reduced ␣ 2 Na ϩ pump expression, and smooth muscle-specific overexpression of NCX1 all induce hypertension. Furthermore, ouabain and reduced ␣ 2 Na ϩ pump expression increase myogenic tone in isolated mesenteric small arteries in vitro, thereby tying these effects directly to the elevation of blood pressure. Thus, endogenous ouabain, and vascular ␣ 2 Na ϩ pumps and NCX1, are critical links between salt and hypertension. New pharmacological agents that act on these molecular links have potential in the clinical management of hypertension.ouabain; Na ϩ pump; Na/Ca exchanger; Ca 2ϩ ; myogenic tone HYPERTENSION, DEFINED AS A diastolic blood pressure (BP) Ն 90 mmHg and/or systolic BP Ն 140 mmHg, is endemic in Westernized societies. This is a very important public health issue because hypertension is a major risk factor for premature death and disability from heart attack, heart failure, stroke, and many other afflictions (16,59). In the United States, alone, Ϸ20% of the population (i.e., Ϸ50 million individuals) are hypertensive; moreover, more than half of all individuals over the age of 60 years have hypertension. In a small fraction of cases, the hypertension is due to specific causes, such as renal vascular disease or excessive secretion of aldosterone (primary aldosteronism) or catecholamines (pheochromocytoma). The vast majority (Ϸ90%) of patients, however, have elevated BP of unknown cause; hence the terms, primary or essential hypertension. The immediate cause for the elevated BP in nearly all chronic hypertensive persons is excessive narrowing of the small (resistance) arteries. Nevertheless, a key question in any discussion of hypertension is: What specific mechanisms actually lead to the abnormal arterial constriction and elevation ...

show abstract

Bovine adrenocortical cells in culture synthesize an ouabain-like compound

Cited by 62 publications

References 30 publications

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

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

Advances in understanding the role of cardiac glycosides in control of sodium transport in renal tubules

How does salt retention raise blood pressure?

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