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Effect of rubidium, lithium and cesium on brain ATPase and protein kinases.

The authors studied the effect of rubidium, lithium and cesium on the ATPase system and c-AMP protein kinase in brain. They demonstrated that rubidium could replace potassium in the Na+K-ATPase system, whereas lithium and cesium had no effect on this enzyme activity in the absence of potassium. K+-dependent ATPase was activated by even low rubidium concentrations; lithium and cesium inhibited it. None of three (rubidium, lithium and cesium) affected c-AMP protein kinase.

Adenosine Triphosphatases↗

Rubidium shows effects different from lithium on phosphatidylinositol metabolism in a cell line of human neuroblastoma.

In a SK-N-BE human neuroblastoma cell line the incubation of rubidium (1 and 10 mM) for 24 h significantly increased IP2 formation, whereas it apparently did not affect other inositol phosphates. In comparison to lithium (10 mM), which significantly enhanced inositolmonophosphate and IP2 accumulation following carbamoylcholine (1 mM) stimulation, rubidium at the same concentration, was unable to affect inositol phosphate accumulation. In conclusion, the present experiments show that rubidium, compared with lithium, shows a different profile on phosphoinositide metabolism since its main action is an increase in phosphatidylinositol turnover. These results may have some relevance to the use of rubidium as antidepressant in man.

Cell Line↗

Proton-activated rubidium transport catalyzed by the sodium pump.

Although the sodium pump normally exchanges three sodium for two potassium ions, experiments with inside-out red cell membrane vesicles show that the stoichiometry is reduced when the cytoplasmic sodium concentration is decreased to less than 1 mM. The present study was designed to gain insight into the question whether other monovalent cations, particularly protons, can act as sodium congeners in effecting pump-mediated potassium transport (ATP-dependent rubidium efflux from inside-out vesicles). The results show that at low cytoplasmic sodium concentration, an increase in proton concentration effects a further reduction in sodium:rubidium stoichiometry, to a value less than the minimal expected (1Na+:3Rb+). Furthermore, when vesicles containing 86RbCl are incubated in nominally sodium-free medium. ATP-dependent net rubidium efflux (normal influx) occurs when the pH is reduced from approximately 7.0 to 6.2 or less. This efflux is inhibited by strophanthidin and vanadate. These experiments support the notion that the sodium pump can operate as an ATP-dependent proton-activated rubidium (potassium) pump without obligatory countertransport of sodium ions.

Adenosine Triphosphate↗

[Transmembrane effects in the sodium pump system. I. The effect of external potassium and rubidium on the dependence of sodium efflux on sodium concentration in the frog muscle].

The dependence of sodium efflux on intracellular sodium content with various potassium and rubidium concentration in the external medium has been studied on frog sartorious muscle. In potassium-sodium-free magnesium medium ouabain-sensitive sodium efflux was shown to be proportional to internal sodium concentration. In the presence of external ribidium (0.5--5.0 mM) the efflux concentration relations are non-linear, being closely described by assuming that 3 Na+ are transported per pump cycle. In sodium loaded muscles the efflux concentration curve was found to be dependent on the external rubidium concentration, becoming linear instead of S-shaped with the decrease in internal rubidium concentration from 5.0--2.5 to 1.0--0.5 mM. The apparent affinity constant for the internal sodium pump site increased with increasing the external rubidium (potassium) concentration. The data obtained may contribute to the kinetic evaluation of the type of Na-K pump mechanism, being more consistent with simultaneous model of pump operation.

Animals↗

Effects of rubidium on contractility and sodium pump activity in guinea-pig ventricle.

Inhibition of the Na+-K+ active transport system has been postulated to be one mechanism through which myocardial contractility is increased. Rubidium is one substance which has been shown to increase the contractility of guinea-pig atria and inhibit the activity of the isolated Na+,K+-adenosine triphosphatase of guinea-pig ventricle. A reexamination of these results confirmed the positive inotropic effect of rubidium on guinea-pig atria and demonstrated that this effect on contractility is accompanied by a decrease in both resting potential and action potential duration. However, it was also found that rubidium produced a transient negative inotropic effect in guinea-pig ventricle. The latter response was closely paralleled by a transient shortening of action potential duration. A concentration of rubidium maximally effective in decreasing contractility (2.0 mM) had no effect on the slow response action potential or contraction. RbCl (0.1 mM) had no effect on cyclic adenosine 3':5'-monophosphate levels of the ventricle or atrium. RbCl did inhibit active transport in the ventricle, as evidenced by a significant reduction in the electrogenic contribution on the active transport system to the maximal diastolic membrane potential during high-frequency drive. These results demonstrate that RbCl has different effects on the contractility of atrial and ventricular muscle. They also suggest that inhibition of the sodium pump is not necessarily accompanied by an increased force of myocardial contraction.

Action Potentials↗

Myocardial perfusion with rubidium-82. II. Effects of metabolic and pharmacologic interventions.

In order to validate a new method for quantifying coronary blood flow, we injected intravenously a bolus of rubidium-82 (Rb-82) into 28 open-chested dogs under a wide range of flow and physiologic conditions, using beta probes to monitor myocardial radioactivity. Extraction fraction and perfusion were measured using a functional model that separates the data into the free and trapped myocardial rubidium. Extraction and uptake of rubidium were lower during acidosis than during alkalosis and were unchanged by glucose-insulin, digoxin, or propranolol. Myocardial flow, as indicated by rubidium, correlated linearly with simultaneous measurements of flow by microspheres in the same sample volume over a wide range of flow (r = 0.97, n = 106, range 0.02-7.76 ml/min/g). Regional myocardial blood flow can be accurately determined using generator-produced Rb-82. Studies using current state-of-the-art, fast positron-emission tomographic cameras are required to determine the utility of this approach in man.

Animals↗

Single-Crystal Raman Spectroscopy of the Rubidium Alums RbM(III)(SO(4))(2).12H(2)O (M(III) = Al, Ga, In, Ti, V, Cr, Fe) between 275 and 1200 cm(-)(1): Correlation between the Electronic Structure of the Tervalent Cation and Structural Abnormalities.

Low-temperature single-crystal Raman spectra for RbM(III)(SO(4))(2).12H(2)O (M(III) = Al, Ga, In, Ti, V, Cr, Fe) and RbM(III)(SO(4))(2).12D(2)O (M(III) = Al, V) have been collected and assigned in the range 275-1200 cm(-)(1). These results permit classification of the Ti and V rubidium sulfate alums to the beta modification, whereas the remaining tervalent cations give the expected alpha modification. The dimorphism of the rubidium sulfate alums is explained in terms of the electronic structure of the tervalent cation, where the observation of the beta modification is associated with unequal occupancy of the t(2g) (O(h)()) orbitals. For the rubidium vanadium alums the (3)E(g) <-- (3)A(g) electronic Raman (eR) transition permits quantification of the trigonal field splitting of the t(2g) (O(h)()) orbitals (ca. 1940 cm(-)(1)). The profile of the eR band is sensitive both to changes in temperature and to deuteration. Analysis of the eR band profile suggests a reduced spin-orbit splitting of the (3)E(g) manifold, this being ascribed to excited state Jahn-Teller (J-T) effects. The similarity of the Raman spectra of the cesium and rubidium titanium sulfate alums suggest that they exhibit closely related structural chemistry, with both subject to phase transitions below 80 K. The observation that modes of E(g) symmetry are coupled to the structural change is consistent with the interpretation that the trigonal field leaves an orbital doublet ground term for titanium(III), leading to a cooperative J-T effect.

Journal Article↗

Inhibition of activity in rats by rubidium chloride.

Effects of two dosages of rubidium chloride on exploration, locomotion, rearing and immobility were assessed for male and female rats in an exploration box and an open field. In contrast to previous findings, rubidium was found to decrease locomotion and rearing in the exploratory box, and also to decrease locomotion in the open field. Further research in a variety of experimental settings is required before the effects of rubidium on activity can be fully evaluated.

Animals↗

Effects of lithium and rubidium on shock-induced changes in open-field activity.

Lithium chloride and rubidium chloride were tested under conditions in which the effects of their chronic administration on aversively-controlled behavior could be assessed. Lithium attenuated shock-induced suppression of open-field activity when that suppression was under the control of mild or moderate stimulus parameters, but had no effect on the suppression produced by the presence of shock itself. Rubidium, on the other hand, increased shock-induced suppression under all conditions. When shock was removed and extinction of the activity suppression was investigated, lithium subjects failed to return to their original baseline activity levels, while subjects receiving rubidium recovered baselines in a manner indistinguishable from that observed in control animals.

Animals↗

Determination of rubidium in human serum.

Field desorption mass spectrometry (FD-MS) combined with stable isotope dilution has been used to determine rubidium concentrations from human serum. Samples obtained from 110 healthy volunteers (50 males, 60 females) were examined. The rubidium concentrations found varied from 0.96 to 3.56 mumoles/l, the average value being 1.96 mumoles/l. The precision of the measurements within a batch was 0.8%. The time for 1 analysis, including sample preparation is about 30 min, the total sample consumption is 100-200 mul. The corresponding potassium concentrations were also determined from all these serum samples; a weak trend towards higher potassium levels with increasing rubidium concentration is found.

Female↗

Rubidium in psychiatry: research implications.

A brief overview of the use of rubidium in affective disorders and schizophrenia is presented. Although antidepressant action of rubidium has not been supported by adequate number of controlled studies, its potential contribution to psychiatry warrants further investigations. Endogenous rubidium may be a useful research tool in the future psychopharmacological studies of affective disorders.

Antidepressive Agents↗

Determination of lithium and rubidium in physiological fluids and tissues of rabbits during the reproductive phase.

1. The natural concentrations of lithium and rubidium were determined during the reproductive phase of rabbits by field desorption mass spectrometry. 2. Samples of serum, milk, amniotic fluid and placenta tissue were analysed. 3. The concentration changes in serum during the reproductive phase were between 2.61 and 5.02 micrograms/l for lithium and between 107.78 and 136.28 micrograms/l for rubidium. 4. Correlations between the concentration in maternal serum and bone growth of the fetus as well as the formation of milk were found. 5. Concentrations of 9.30 micrograms/l lithium and 1780.00 micrograms/l rubidium in the milk lead to the assumption that these trace metals are essential for the metabolism of the young rabbit.

Amniotic Fluid↗

The effect of acute lithium and rubidium pretreatment on apomorphine-induced pecking in pigeons.

The effects of different doses of lithium (5-320 mg/kg intramuscularly) and rubidium (0.25 32 mg/kg intramuscularly) on apomorphine-induced pecking were investigated in pigeons. These two cations did not induce pecking by itself. Intramuscular administration of apomorphine (a mixed D1/D2 dopamine receptors agonist, 0.1-1.6 mg/kg) induced pecking in a dose-dependent manner. SCH 23390 (D1 dopamine receptor antagonist, 0.02-0.08 mg/kg) and sulpiride (D2 dopamine receptor antagonist, 25-100 mg/kg) decreased apomorphine-induced pecking dose-dependently. Combination of SCH 23390 (0.04 mg/kg) with sulpiride (50 mg/kg) caused a stronger inhibitory effect on apomorphine response. This indicates that both D1 and D2 dopamine receptors are involved in apomorphine-induced pecking. The response induced by apomorphine (0.2-0.8 mg/kg) was decreased in animals pretreated with lithium and rubidium. In these conditions, SCH 23390 and sulpiride produced a larger inhibitory effect on the apomorphine response, suggesting that acute lithium and rubidium pretreatment inhibit pecking by interfering with dopaminergic mechanisms.

Animals↗

Accumulation of caesium and rubidium in vivo by red and white muscles of the rat.

1. Rats were given drinking water containing either 20 mM-CsCl or 20 mM-RbCl for a period of 2 weeks. Samples of blood were then taken from the rats under anaesthetic. They were immediately centrifuged and the plasma taken for analysis. Soleus muscles, diaphragm, extensor digitorum longus, white gastrocnemius and vastus lateralis muscles were then taken from the dead animals and these and the plasma were analysed for potassium, and for caesium or rubidium by means of the flame photometer.2. The concentrations of potassium and rubidium or caesium in the fibre water of these various muscles and in the samples of plasma water were then calculated.3. It was found that the red muscles including soleus and diaphragm generally tended to accumulate caesium and rubidium to a greater extent than did the white muscles such as the white gastrocnemius and vastus lateralis.4. When the concentration ratio [K](i)/[K](o) was divided into the ratio [Rb](i)/[Rb](o) for the different muscles, values of about 1.3 were obtained for the red muscles compared with values about 1.14 for white muscles.5. When in the case of the caesium-treated rats the ratio [K](i)/[K](o) was divided into the ratio [Cs](i)/[Cs](o) values ranged from 1.94 +/- 0.12 for the red soleus to 1.08 +/- 0.09 for the white gastrocnemius.6. When these values in the caesium-treated animals were plotted against the percentage of red fibres in the five muscle types (as obtained from the data of Sreter & Woo, 1963) the graph indicated that the white fibres had similar ionic gradients for Cs(+) and K(+) and that affinity for Cs(+) was confined to the red fibres.7. The membrane potential measured in soleus and extensor muscles immersed in plasma from the same animal was not significantly different from E(K) but was much less than E(Cs).8. These results are interpreted in terms of permeability differences between the slow red fibres and white twitch fibres.

Animals↗

Rubidium influx into rat skeletal muscles in relation to electrical activity.

1. Rates of (86)Rb influx were compared in vivo over 2, 4 and 6 hr periods in various tonic and phasic muscles of rat following its I.P. injection. During the 2 hr period its influx rate into soleus was about 4 times that of the vastus with the EDL muscles at an intermediate rate. Uptake by diaphragm was fastest reaching equilibrium within 2 hr.2. Unilateral section of the sciatic nerve 48 hr before (86)Rb injection reduced isotope uptake into soleus to about 50% of its contralateral control muscle over a 4 hr period. In EDL muscles on the other hand nerve section increased influx by about 75% of control in conscious rats and more than doubled influx in anaesthetized rats.3. Tenotomy of soleus reduced (86)Rb influx to 40% of control, but tenotomy in EDL was without effect in influx.4. Uptake of urea into muscles within 5 min of its I.V. injection was used to determine the possibility of muscle blood flow determining (86)Rb influx. Accumulation of urea was not significantly different in control and denervated EDL muscles nor between soleus and vastus muscles in anaesthetized rats, so it seems unlikely that blood flow is important here.5. Membrane depolarization in response to addition of 30 mM rubidium to external bathing fluid was greater in the case of denervated than in control EDL muscles which was in keeping with the greater (86)Rb influx seen in the former muscles. The ouabain sensitivity of rubidium-induced depolarization in the denervated EDL muscles would suggest, however, that rubidium enters the fibres actively.

Animals↗

Rubidium and lithium: opposite effects on amine-mediated excitement.

In mice the activation caused by morphine was antagonized by previous treatment with lithium and was potentiated by previous treatment with rubidium. Other antimanic drugs antagonized the morphine activation as well. The effect of rubidium was similar to that of the antidepressant drugs imipramine and pargyline. Rubidium may merit clinical evaluation as an antidepressant agent in man.

Animals↗

Clearance of 9-micron spheres and rubidium in the intestinal circulation.

Rubidium clearance and 9-micron-sphere entrapment were studied and compared in isolated intestinal preparations under various physiological conditions in 10 dogs anesthetized with intravenous pentobarbital sodium. The chosen intestinal segment was pumped with aortic blood at a constant rate and pressure of about 90-100 mmHg. The temperature of the isolated loop was maintained at 37-38 degrees C with an electrical pad. A mixture of 86Rb and 9-micron-spheres labeled with 141Ce was injected into the arterial cannula supplying the intestinal loop while mesenteric venous blood was collected for activity counting. Three to four intestinal segments were used from each dog. The following three experimental conditions were randomly used for each intestinal segment preparation: 1) a mesenteric venous pressure (MVP) equaling 0 cmH2O and warmed normal saline infused into the lumen of segment; 2) an MVP equaling 0 cmH2O and 5% glucose in saline infused into the intestinal lumen; and 3) the reservoir with venous blood elevated to provide an MVP equaling 17 cmH2O and warmed normal saline infused into the intestinal lumen. A very strong and significant correlation was found between rubidium and microsphere clearances (r = 0.99, P less than 0.0001). Rubidium extraction was inversely associated with blood flow through the intestinal segment (r = 0.49, P = 0.02), while microsphere entrapment (extraction) was independent from intestinal blood flow (r = 0.16). The data suggest that the shunting of 9-micron spheres through tissue reflects the arteriovenous shunting of blood and, therefore, can be used as a tool to study the nutritive and nonnutritive blood flows in tissues.

Animals↗

Noninvasive quantification of regional myocardial perfusion with rubidium-82 and positron emission tomography. Exploration of a mathematical model.

Positron emission tomography (PET) centers without cyclotrons use generator-produced rubidium-82 (82Rb) for assessment of myocardial perfusion. The aim of the present study was to determine whether myocardial blood flow could be assessed quantitatively with 82Rb and PET. Because the myocardial extraction fraction of 82Rb varies inversely and nonlinearly with flow and cannot be measured conveniently with PET, we used an experimentally derived mathematical function defining the relation between single-pass extraction fraction of 82Rb and flow to obviate the necessity of measuring the extraction fraction directly. Myocardial blood flow in absolute terms (ml/g/min) was estimated from dynamic PET scans after intravenous administration of 82Rb in intact dogs and compared with flows measured with radiolabeled microspheres. In 36 comparisons in 13 dogs studied at rest, or after coronary occlusion, reperfusion, or after coronary hyperemia induced with intravenous dipyridamole, over the flow range from 0.2 to 2.0 ml/g/min, estimates of perfusion with rubidium correlated well with flows measured concomitantly with microspheres, although there was a slight underestimation of flow with rubidium (flow by 82Rb = 0.92 x flow by microspheres-0.021, r = 0.83). In general, estimates of flow in ischemic regions were less reliable than estimates for regions with normal flow. Thus, although the relation between myocardial extraction and retention of 82Rb and flow can vary under a variety of physiological and pathophysiological conditions, this study demonstrates the ability to obtain quantitative estimates of myocardial blood flow with 82Rb and PET under carefully defined conditions without measuring the extraction fraction directly.

Animals↗