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Biomedical subjects

E Erdmann

Publications and source records attributed to E Erdmann.

At least 415 records · Page 23Linked to original sources
PubMed1979

[Quantitative aspects of specific binding of cardiac glycosides to membrane receptors].

Although the exact mechanism of positive inotropic action of cardiac glycosides is unknown, specific membrane bound proteins with high affinity for this group of drugs have been characterized. These "receptors" for cardiac glycosides have been measured quantitatively in cardiac tissue of humans and several species as well as in other tissues. The occupation of receptors by cardioactive steroids has been found to agree quantitatively with the drug effects in respect to inhibition of (Na+ + K+)-ATPase and in respect to positive inotropy (these experiments were performed in electrically stimulated contracting cardiac muscle). Changes in receptor concentration or receptor properties have been observed in hyperthyroidism, chronic hypokalaemia, thalassaemia or in acutely changed serum concentrations of K+, Ca++ and several drugs. These changes may be of great significance in patients treated with cardiac glycosides as their effects are not reflected by the serum concentration of cardiac glycosides. The understanding of drug-receptor-interactions on the molecular level--especially under the pathological conditions in the patient--will increase our diagnostic and therapeutic knowledge.

Calcium↗
PubMed1978

Effect of some Pteridine compounds on the Na+ + K+)-ATPase and on the cardiac glycoside receptor of human heart).

Pteridine compounds are known to block Na+-reabsorption and K+-secretion in epithelial cells (salivary duct of the rat), which actively transport Na+ and K+ against an electrochemical gradient. Furthermore, there have been reports on antagonistic effects of these substances in digitalis induced arrhythmias. Therefore the actions of triamterene (Jatropur, Dyrenium), the sulfuric acid ester and the methylether of p-hydroxytriamterene (OH-triamterene) and OH-triamterene on specific [3H] g-strophanthin (ouabain) binding and Na+ + K+)-ATPase activity of isolated human cardiac cell membranes were investigated. Triamterene, the sulfuric acid ester and the methylether of OH-triamterene inhibit (Na+ + K+)-ATPase activity only at very high concentrations (10(-5)--10(-4) M). OH-Triamterene does not inhibit this enzyme at concentrations lower than 10(-3) M. The specific binding of [3H] g-strophanthin to human cardiac cell membranes is inhibited half maximally at relatively high concentrations, too (10(-5)--10(-4) M). These results are rather indicative of unspecific effects due to membrane sites of action other than the (Na+ + K+)-ATPase or the cardiac glycoside receptor.

Adenosine Triphosphatases↗
PubMed1977

[Cardiac effects of antikaliuretic diuretics-clinical and biochemical investigation (author's transl)].

Recently direct myocardial effects of antikaliuretic diuretics with respect to contractility parameters and prevention of digitalis-induced arrhythmias were published. In order to test the value of these reports we measured the effect of potassium-canrenoate and triamterene on cardiac output and on digitalis-induced arrhythmias in patients during diagnostic and the therapeutic flow directed right heart catheterization (Swan-Ganz) in our intensive care unit. In addition the influence of these drugs on (Na+ + K+)-ATPase and on (3H)g-strophanthin binding to human cardiac cell membranes was investigated to gain information on the mechanism of their action. Triamterene (100-200 mg p.o.) was without any effect on cardiac output, the same was found true for potassium-canrenoate given in a single dose (200-1000 mg intravenously). However, when applied in two doses (200 mg i.v. and 60 min later 400 mg i.v.), potassium-canrenoate increased cardiac output by 11 percent (p less than 0.05). Only in 2 out of 14 patients potassium-canrenoate (200-400 mg i.v.) suppressed digitalis-induced ventricular ectopic beats. Canrenone, the active metabolite of potassium-canrenoate displaces [(3H)]g-strophanthin from its binding sites in human cardiac cell membranes and inhibits (Na+ + K+)-ATPase activity. These in vitro effects were measured at the same concentrations as found in vivo after "therapeutical" doses. The effects of triamterene in this respect were found only in extremely high concentrations. Our results imply that canrenone has cardiac glycoside-like effects in human cardiac cell membranes.

Adenosine Triphosphatases↗
PubMed1976

Ouabain-receptor interactions in (Na+ + K+)-ATPase preparations. A contribution to the problem of nonlinear Scatchard plots.

Specific [3H]ouabain binding to rat and guinea pig skeletal muscle (musculus soleus) was studied using a rapid centrifugation and a filtration method. Both assays gave identical results: the incubation of the cell membranes in 50 mM imidazole/HCl buffer pH 7.25 or 7.4 MgCl2, Pi caused a time dependent loss of (Na+ +K+)-ATPase activity indicating an alteration of the membrane preparation. Ouabain binding properties were changed concomitantly. If ouabain binding was allowed to proceed until equilibrium was reached (3 min in rat and 10 min in guinea pig) at 37 degrees C the data plotted according to Scatchard followed a straight line. The dissociation constants of the ouabain-receptor-complexes of the rat cell membrane preparation as calculated from the slope of the plot (KD = 134 nM) and from the ratio of the dissociation and association rate constants (KD = 175 nM) agreed within experimental error with that determined by Clausen and Hansen [(1974) Biochim. Biophys. Acta 345, 387-404] in intact soleus muscles (KD = 210 nM). If ouabain binding was allowed to proceed for a longer period, however, nonlinear Scatchard plots resulted with an identical maximal number of binding sites but inconstant and decreased affinity for the cardiac glycoside. Experimental evidence is presented that nonlinear Scatchard plots often obtained in hormone (drug)-receptor binding experiments may (among other things) be the result of damaged cell membrane particles in vitro.

Adenosine Triphosphatases↗
PubMed1976

[The effect of potassium on ouabain-binding to human cardiac cell membranes (author's transl)].

The concentration of cardiac glycosides in the serum of an individual patient does not necessarily correlate strictly with the known effects or side effects of these drugs. It is good clinical experience for instance that an acutely decreased serum potassium concentration due to diuretic therapy or dialysis may cause severe digitalis-induced arrhythmias in spite of an unchanged serum glycoside level. On the other hand digitalis intoxication often is treated successfully by the application of potassium. These observations prompted us to investigate the specific binding of tritiated g-strophanthin to isolated human cardiac cell membranes in the presence of different potassium concentrations. Potassium in a concentration-dependent manner displaces ouabain from its binding sites by decreasing the affinity of the receptor for the drug. However, the number of receptor sites remains constant. When analysing the association and dissociation rates of the ouabain-receptor complex it was found that potassium inhibits the binding process only, without affecting the dissociation. At least up to a concentration of 5 mM the potassium induced displacement of ouabain from its binding sites seems to be competitive. These in vitro measurements of the strophanthin--receptor interactions agree with clinical observations and are helpful in their explanation.

Binding, Competitive↗
PubMed1976

[Significance of serum digoxin concentration and its influencing factors].

In recent years it has become possible by means of a radioimmunoassay to measure Digoxin concentration in the serum of digitalized patients. With this method it could be shown that the resorption of Digoxin is decreased by partial resection of the samll intestines, by malabsorption syndromes, after ingestion of Neomycin, Colestyramine and antacids. In renal insufficiency, however, the elimination half-life period of Digoxin is increased conspiciously (from about 35 hours up to about 120 hours). This results in a raised serum concentration of cardiac glycosides unless the dosage is decreased considerably. The incidence of Digitalis intoxication in Digitalis treated patients has been reported to rank as high as 20%. There is, however, no strict correlation between the serum glycoside level and the clinical symptoms, because the glykoside concentration in the serum does not represent the pharmacologically active concentration at the receptor. Experimental investigations of cardiac glycoside binding to the receptor for cardiac glycosides in human heart cell membranes revealed, that receptor bound Digoxin for instance is diminished in serious renal insufficiency and it depends on the serum concentration of potassium, calcium and magnesium. In hypoxia, after myocardial infarction and in myxedema the sensitivity for cardiac glycosides is increased. The opposite is true in hyperthyreoidism, fever and in children. All of these factors have to be kept in mind and paid attention to in the clinical evaluation of the measured Digoxin concentration in the serum.

Cardiac Complexes, Premature↗