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Biomedical subjects

W Krawietz

Publications and source records attributed to W Krawietz.

At least 37 records · Page 2Linked to original sources
PubMed1984

Cardiac glycoside binding sites in cultured heart muscle cells.

Binding of (3H)-ouabain to cultured cardiac muscle and non muscle cells from chicken embryos and neonatal rats has been characterized and correlated with ouabain-induced inhibition of the sodium pump, as well as with the positive inotropic action of the drug. Cardiac muscle and non muscle cells from 10-12 day-old chicken embryos are characterized by a single class of ouabain binding sites (muscle cells: dissociation constant KD = 1.5 X 10(-7) M; binding capacity B = 2.6 pmoles/mg cell protein). Two classes of ouabain binding sites, however, have been found in cardiac muscle and non muscle cells from 1-3 day-old, neonatal rats (muscle cells: high affinity, low capacity sites: KD = 3.2 X 10(-8) M, B = 0.2 pmoles/mg protein; low affinity, high capacity sites: KD = 1.7 X 10(-6) M, B = 2.6 pmoles/mg protein). Half maximal inhibition of active (86Rb+ + K+)-influx occurs at 5.8 X 10(-7)M ouabain in chicken heart muscle cells and at 1.3 X 10(-5)M in rat heart muscle cells [( K+] = 0,75 mM). Decreases in cell-K+ (EC50 = 6.7 X 10(-7)M and 1.9 X 10(-5)M) and increases in cell-Na+ (7.4 X 10(-7) and 10(-5) - 10(-4)M) parallel ouabain-induced inhibition of the sodium pump. Up to 10(-6)M, ouabain does not affect velocity of cell wall motion in cultured rat heart muscle cells. A concentration-dependent increase in cell wall motion is observed at concentrations between 5 X 10(-6) and 5 X 10(-5)M, being indicative of a positive inotropic effect. At 10(-4)M ouabain, arrhythmias are present. Our data demonstrate the existence of one single class of cardiac glycoside receptors in cultured cardiac muscle cells from chicken embryos.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1982

Effect of vanadium in the +5, +4 and +3 oxidation states on cardiac force of contraction, adenylate cyclase and (Na+ + K+)-ATPase activity.

The influence of vanadium in the nominally +5 (NH4VO3; referred to as V5+), +4 (C10H14O5V and VOSO4; V4+) and +3 oxidation states (VCl3; V3+) on cardiac force of contraction, adenylate cyclase and (Na+ + K+)-ATPase activity was investigated in order to determine which form of vanadium mediates the cardiac effects. V5+, V4+ and V3+ (300 microM each) increased the force of contraction of isolated electrically driven cat papillary muscles by about 100%. In the presence of the reducing agent ascorbic acid (5 mM) none of the three compounds led to any distinct increase in force of contraction. On the particulate adenylate cyclase preparation from feline right ventricles only V5+ stimulated the enzyme activity by about 100%, whereas V4+ and V3+ were ineffective. In the presence of 5 mM ascorbic acid all three compounds were ineffective. In contrast, in the presence of the oxidizing agent diamide (azodicarboxylic acid-bis-dimethylamide; 1 mM) all three compounds became stimulatory. On the isolated (Na+ + K+)-ATPase V5+ (500 microM) alone reduced the basal activity by about 95%. In the presence of ascorbic acid the inhibitory effect of V5+ was greatly diminished. Similar results were obtained with V4+, V3+ (100 microM) alone inhibited (Na+ + K+)-ATPase activity only by about 40%. In the presence of ascorbic acid V3+ was ineffective. From the results it is concluded that positive inotropism, stimulation of adenylate cyclase and inhibition of (Na+ + K+)-ATPase by vanadium compounds likewise result from an action of vanadium in the +5 oxidation state.

Adenylyl Cyclases↗
PubMed1982

Stimulatory (insulin-mimetic) and inhibitory (ouabain-like) action of vanadate on potassium uptake and cellular sodium and potassium in heart cells in culture.

(1) The influence of vanadate (Na3VO4) on sodium and potassium uptake as well as on cellular ion contents of sodium and potassium has been studied in heart muscle and non-muscle cells obtained from various species. An ouabain-like inhibition of potassium uptake (up to 50%), combined with a decrease of cellular potassium (up to 20%) has been observed by vanadate (10(-4)-10(-3) M) in heart non-muscle cells obtained from neonatal guinea pigs and chick embryos. In heart muscle and non-muscle cells prepared from neonatal rats, as well as in Girardi human heart cells, a vanadate-induced stimulation of potassium uptake (up to 100%), combined with a rise in cellular potassium (up to 20%) and without significant alteration of cellular sodium, has been found. A slight increase of 22Na+ influx can be measured in rat heart muscle cells and in Girardi human heart cells in the presence of vanadate (10(-4)--10(-3) M). (2) In beating rat heart muscle cells in culture, detrimental effects of serum deprivation--concerning beating properties, potassium uptake and cellular potassium--can at least in part be overcome by addition of vanadate. Furthermore, this compound prevents ouabain-induced signs of toxicity (contractures) in these cells. (3) The stimulatory effects of vanadate on potassium can be mimicked by insulin (1-10 mU/ml). Furthermore, vanadate produces an insulin-like stimulation of 2-deoxy-D-glucose uptake in rat heart muscle and non-muscle cells as well as in Girardi human heart cells. (4) The experimental data demonstrate an ouabain-like inhibition as well as an insulin-mimetic stimulation of potassium-uptake in various heart cells. The reason for this antagonistic mode of action may be due to the different capabilities of the heart cell types to reduce vanadium in the V-valence state of vanadium in the IV-valence state, thereby favouring either ouabain-like inhibition (vanadium V) or insulin-mimetic stimulation (vanadium IV) of potassium transport.

Animals↗
PubMed1982

Vanadate stimulates adenylate cyclase via the guanine nucleotide regulatory protein by a mechanism differing from that of fluoride.

Vanadate stimulates adenylate cyclase activity in turkey erythrocyte membranes. The maximal stimulation is 7-fold over basal at 3 mM vanadate; higher concentrations are inhibitory. A suboptimal concentration of fluoride (1 mM) together with vanadate (3 mM) activates adenylate cyclase in a non-additive manner; cyclase activation by optimal fluoride (10 mM) is inhibited by vanadate (3 mM). There is no stimulation by vanadate of adenylate cyclase activity (measured either with Mg2+ or Mn2+) in CYC- S49 lymphoma cell membranes. Vanadate (3 mM) shows no effect on binding of Beta-adrenergic agonists or antagonists to the [3H] (-)-dihydroalprenolol binding site in turkey erythrocyte membranes. These results suggest that the effect of vanadate on Adenylate cyclase is mediated through the nucleotide regulatory protein and may act by a mechanism similar to fluoride. However, in cholera toxic-treated membranes as well as in GDP-beta-S plus isoproterenol-treated membranes, fluoride-stimulated adenylate cyclase activity is significantly reduced, but vanadate stimulation is not. Our results suggest that although the actions of vanadate and fluoride in adenylate cyclase may each involve the nucleotide regulatory unit, the exact mechanisms of activation by the two anions differ.

Adenylyl Cyclases↗
PubMed1980

Effects of vanadate in cultured rat heart muscle cells. Vanadate transport, intracellular binding and vanadate-induced changes in beating and in active cation flux.

Cultured rat heart muscle cells have been used to study uptake and intracellular binding of Na483VO4 (vanadate), as well as the influence of vanadate on beating and 86Rb+ uptake of these cells. 1. Vanadate is taken up into cultured rat heart muscle cells in an energy-independent manner by a saturable transport system (Km approximately 60 microM, V approximately 200 pmol per mg protein per min at 37 degrees C). Analysis of intracellular binding of vanadate reveals a curved Scatchard plot indicating more than one binding site. Maximal binding amounts to 3 . 10(9) molecules of vanadate per cell. 2. Vanadate exerts a positive chronotropic and inotropic effect and increases automaticity. First effects can be seen at 1 . 10(-7) M Na3VO4. Concentrations higher than 1. 10(-3) M induce toxic effects (arrhythmias, fibrillation and stand-still of the cell). 3. Vanadate-induced alterations of beating is paralleled by a vanadate-induced stimulation of (86Rb+ + K+) uptake into the cells of up to 75%. Maximal stimulation is obtained at concentrations of 1 . 10(-4)--1 . 10(-3) M vanadate. The stimulation is thought to be due to an increased activity of (Na+ + K+)-ATPase, since it can be inhibited by ouabain. This result is in contrast to in vitro experiments with purified membrane preparations of (Na+ + K+)-ATPase of different organs, where an inhibition of (Na+ + K+)-ATPase by vanadate has been found. 4. The results indicate a possible role of vanadate as an endogenous regulator of active cation flux in heart tissue.

Animals↗
PubMed1980

Is the determination of serum digoxin concentration useful for the diagnosis of digitalis toxicity?

In a prospective symptom-oriented study, patients with (n = 81) or without (n = 206) digoxin toxicity were not discernible on their serum digoxin concentration (SDC) because of a large overlap between toxic and non-toxic groups. There was, however, a significant difference between the mean values of the groups (p < 0,01). Serum creatinine, the presence or absence of ischemic heart disease, and/or chronic pulmonary heart disease were significantly different (both p < 0,025) between toxic and non-toxic groups. It is concluded that a decision on digitalis toxicity should be made by a synopsis of the influencing factors in the individual case. Dosage, serum creatinine and cardiac status seem to be the most important factors to be taken into account. Lack of agreement between SDC and digoxin effects could be demonstrated in differences in "T 1/2" between SDC and the normalisation of prolonged PQ-time after digoxin withdrawal. The inability of the SDC to describe all alterations important for digitalis effects and side effects seems to be that it does neither mirror the glycoside concentration at the receptor site, nor the changes of receptor affinity, nor the changes of (Na+ + K+)-ATPase activity.

Aged↗