Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Digitalis-like compounds (DLC), constituents of animal tissues, are possible regulators of the Na+, K(+)-ATPase implicated in water and salt homeostasis. The distribution of DLC in the toad (Bufo viridis) was determined following methanol extraction and partial purification. DLC highest levels were found in the skin but it was also detected in the plasma and many internal organs. Short term (hours) exposure of the toad to hypertonic shock (1.5% NaCl) induced an increase in plasma osmolarity due to an increase in Na+ and Cl- levels. This treatment induced a transient, three fold, increase of DLC levels in the brain and transient reduction of its levels in the ventral skin. Acclimation of the toads to burrowing conditions for six weeks resulted in an increase in plasma osmolarity due to a large increase in plasma urea with a small increase in ion concentrations. Under these conditions DLC levels in the dorsal skin increased by 100% without alteration of its levels in the plasma, brain and ventral skin. DLC levels in the toad brain of control animals, showed a significant dependence on season, being highest in the summer and lowest in the winter. DLC levels in the skin peaked in May while the levels in the plasma were season independent. The changes in DLC levels induced by the short- as well as long-term perturbations in the animal environmental salinity together with the seasonal differences suggest that DLC in the toad is involved in water and salt homeostasis of these animals, but may also participate in other unknown functions.
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PMID:Digitalis-like compounds in the toad Bufo viridis: tissue and plasma levels and significance in osmotic stress. 161 77

Digitalis-like substance (DLS) was measured by Na-K-ATPase inhibitor (ATPI) activity and digitalis-like immunoreactivity (DLI) in 100 patients with type II diabetes. Hypertensive diabetic patients with a positive family history for hypertension had high ATPI levels compared with those patients with a negative family history for the disease. DLI level did not differ between groups. There was no significant difference in ATPI and DLI levels among three groups based on level of urinary albumin excretion. These data suggest that a circulating factor (or circulating factors) determined by ATPI may be linked with genetic factors in the development of hypertension, but not to the development of diabetic nephropathy.
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PMID:Elevated endogenous Na-K-ATPase inhibitor activity in hypertensive diabetic patients with a family history of hypertension. 166 15

Digitalis compounds are known to increase Ca2+ influx in various cells. As platelet cytosolic free [Ca2+] and plasma digitalis-like activity have been reported independently to be higher in some untreated hypertensive patients than in normotensive subjects, we have investigated a possible relationship between these two parameters. Platelet cytosolic free [Ca2+], determined using Quin-2, the capacity of plasma extracts to inhibit renal Na+, K(+)-ATPase activity and ouabain binding on human erythrocytes were measured in parallel in 25 untreated hypertensive patients and 11 normotensive subjects. Enhanced values for all 3 parameters were observed in the same hypertensive patient. Platelet cytosolic free [Ca2+] was positively correlated to the plasma digitalis-like activity, which was evaluated by the inhibition of Na+, K(+)-ATPase activity and ouabain binding (r = 0.430, P = .010 and r = 0.448, P = .006, respectively). These relationships were independent of age and blood pressure. These results indicate that endogenous digitalis-like compounds may participate in the control of cytosolic free [Ca2+], in agreement with their proposed hypertensive role.
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PMID:Plasma digitalis-like activity and cytosolic Ca2+ in essential hypertension. 215 64

1. Hypertension is a complication of autologous bone marrow transplantation when therapy includes multiple alkylating agents. We have sought to identify the factors underlying this hypertension. We measured weight, serum creatinine, plasma renin activity, aldosterone and digoxin-like immunoreactive factor (DLIF), by digoxin radioimmunoassay, in 18 patients. Plasma catecholamines were also measured in five patients. 2. Of the 18 patients studied, 15 became hypertensive. The variable most consistently associated with these individuals' hypertension was DLIF activity which was increased in 14 of the 15 hypertensive patients (P = 0.055, Fisher exact test). Serum creatinine was increased at some point in seven of the 15 hypertensive patients, weight was increased in five and plasma renin activity and aldosterone were increased in one. Catecholamines were not increased in any of the five patients in which they were measured. 3. The association between changes in mean arterial pressure (MAP) and changes in DLIF for the group as a whole was assessed by analysing one data pair per patient, representing the maximal MAP. This correlation was significant (r = 0.75, P = 0.001). 4. Within individual patients, changes in MAP and changes in serum DLIF concentrations were significantly correlated (r greater than 0.50, P less than 0.05) in six of 15 hypertensive patients. 5. Digitalis-like factor (DLF) was measured by inhibition of (Na+,K+)-adenosine 5'-triphosphatase in five patients and DLF and DLIF were significantly correlated (r = 0.081, P = 0.0001). DLF and MAP were also significantly correlated (r = 0.59, P = 0.002). 6. This represents the first longitudinal study of the relationship between DLIF and blood pressure in hypertensive individuals, and the results suggest that DLIF may contribute to the increased blood pressure in some of these subjects.
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PMID:Endogenous digoxin-like immunoreactive factor and digitalis-like factor associated with the hypertension of patients receiving multiple alkylating agents as part of autologous bone marrow transplantation. 255 6

Endogenous Digitalis-Like Factor (DLF) is a putative hypothalamic Na+,K+-ATPase inhibitor that mediates natriuresis in response to intravascular volume expansion or sodium loading. The precise structure of this substance remains unknown; however, it cross-reacts with antibody to digoxin. Using a radioimmunoassay, we measured DLF concentrations in 26 normal subjects: mean value of this factor was 0.512 ng digoxin-equivalents/ml +/- 0.038 SEM; DLF correlated significantly with serum sodium levels (r = 0.59 - p less than 0.01) and daily urinary sodium excretion (r = 0.48 - p less than 0.05). Our results confirm that endogenous digitalis-like factor has a physiological role as regulator of natriuresis, in response to plasma sodium concentrations.
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PMID:[Endogenous digoxin-like factor: serum concentration and interrelations with the electrolyte picture in normal subjects]. 256 Sep 23

Adenohypophysis and hypothalamic bovine tissues were homogenized, lipid extracted, salt removed and loaded onto 2 successive mu Bondapak HPLC columns, semipreparative and analytic, respectively. In vitro sodium-pump inhibitory activity, recovered from each tissue, showed similar chromatographic patterns, but hypothalamus seems to contain a major hydrophobic material which appears at the end of the run, when acetonitrile gradient raised 40% approximately. Digitalis-like activity disappears along the purification procedure, and this fact suggests a clear dissociation between (Na/K)ATPase inhibition and digoxin-like activity, measured as crossing with digoxin antibodies.
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PMID:Partial purification of a sodium pump inhibitor from bovine adenohypophysis. Its comparison with the natriuretic factor isolated from hypothalamus. 285 13

Although the therapeutic actions of digitalis glycosides have been known for over 200 years, their direct inotropic actions on the heart were not established until the last 50 years. Digitalis has undergone intense research, particularly with respect to its mechanisms of action. Many authors have claimed to have found the true mechanism of action, compounding the complexity of literature. Recent subcellular studies have pointed to specific areas of action of the digitalis glycosides. Each discovery has been dependent on the greater understanding of the electrophysiologic characteristics of cardiac muscle and excitation-contraction coupling. The current hypothesis suggests that digitalis specifically inhibits Na-K ATPase. This produces an elevation in intracellular sodium level that in turn produces an increase in the intracellular calcium level. The increased quantities of calcium available to the contractile elements of cardiac muscle provide the observed increased inotropy.
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PMID:Cellular mechanisms of digitalis action. 299 96

Digitalis glycosides inhibit Na+K+-ATPase in the cells and have been used for scientific studies of cation transport over cell membranes. Furthermore, digitalis has a positive inotropic and antiarrhythmogenic effect. Specific binding sites for digitalis glycosides have been observed in erythrocytes, the myocardium and the central nervous system. Transcellular transport of digoxin has been found in the kidney, since digoxin is excreted by tubular secretion. Recent studies have discovered an endogenous digitalis-like substance both inhibiting Na-K-ATPase and displacing digoxin from specific binding sites at the erythrocytes. The concentration of this component in plasma seems to be higher in hypertension than in normotension. Future studies will have to disclose other effects of this substance in order to evaluate whether it can be used as a drug in heart failure.
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PMID:Positive inotropic drugs--digitalis. 301 57

Digitalis-like factors were assayed by radioimmunoassay of digoxin in 6 bile samples obtained from patients at autopsy and in plasma from three patients with combined hepatic and acute renal failure. None of the patients received digoxin. Digitalis like factor values in bile samples were 23 to 85 nmol digoxin equivalents/1. Bile salt concentrations ranged from 38-104 mmol/l in the bile and 28-184 mumol/l in the plasma of these subjects. Bile, plasma digitalis like factor extracts and bile salt standards (0.1-3 mM) showed concentration dependent displacement of [125I]-digoxin from digoxin antibody, inhibition of hog brain Na,K-ATPase and displacement of [3H]-ouabain from Na,K-ATPase. The concentration-displacement curves suggest that bile salts could account for 50-79% of the total digitalis like factors in the six bile samples and 2-7% in the plasma of the three patients. High performance liquid chromatographic fractionation of a bile sample showed digitalis like factor peaks co-eluating with standards of tauro- and glycocholate, tauro- and glycochenodeoxycholate and tauro- and glycodeoxycholate. These bile salt peaks accounted for 78% of the total digitalis like factors in all high performance liquid chromatographic peaks in bile, but only 7% of the total digitalis like factor activity in all high performance liquid chromatographic peaks in an extract of plasma from one of the patients with hepatic and renal failure. The bile salts appear to be examples of endogenous digitalis like compounds which do not act by simple competitive ligand binding to antidigoxin antibody and Na,K-ATPase. They make an important contribution to digitalis like factor activity in bile, but not in plasma.
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PMID:Bile salts as endogenous digitalis like factors. 301 98

Congestive heart failure is a complex physiopathological state where both myocardial hypo-contraction and excessive peripheral vasoconstriction lead to lower cardiac output. The increase in cytosolic calcium concentration triggers the contractile processus. Digitalis inhibits the Na+/K+ ATPase enzyme and indirectly increases intracellular calcium concentration. beta 1 agonists increase the synthesis of cAMP-dependent protein kinase and hence the recruitment of new receptor-operated calcium channels which increase the calcium influx and the mobilization from its intracellular storage sites. Vascular smooth muscle contraction occurs with calcium influx into the cell resulting from various receptor activation. In congestive heart failure, activation of the sympathetic nervous system and of the renin-angiotensin system leads to neurohumoral-induced peripheral vasoconstriction. Renal effects of angiotensin II and aldosterone are responsible for sodium and water retention. alpha 1-blocking agents are drugs that block competitively the catecholamines effects on vascular receptors. Angiotensin I-converting-enzyme inhibitors block the formation of the key-element of the system: angiotensin II. Both alpha 1-blocking agents and converting-enzyme inhibitors show vasodilatator effects and acutely improve hemodynamic status of patients with congestive heart failure. Converting-enzyme inhibitors exhibit specific improvement of intrarenal hemodynamics and do not induced sodium and water retention in longterm therapy.
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PMID:[Pharmacological bases of the treatment of cardiac insufficiency]. 303 68


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