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PubMed2004

Structure of the hydrated and dimethyl sulfoxide solvated rubidium ions in solution.

The structure of the hydrated and the dimethyl sulfoxide solvated rubidium ions in solution has been determined by means of large-angle X-ray scattering (LAXS) and extended X-ray absorption fine structure (EXAFS) studies. The models of the hydrated and dimethyl sulfoxide solvated rubidium ions fitting the experimental data best are square antiprisms with Rb-O bond distances of 2.98(2) and 2.98(3) A, respectively. The EXAFS data show a significant asymmetry in the Rb-O bond distance distribution with C(3) values of 0.0076 and 0.015 A(3), respectively. No second hydration sphere is observed around the hydrated rubidium ion. The dimethyl sulfoxide solvated rubidium ion displays a Rb-O-S bond angle of ca. 130 degrees, which is typical for a medium hard electron acceptor such as rubidium.

Cations↗
PubMed1984

A method to quantitate the fractional extraction of rubidium-82 across the blood-brain barrier using positron emission tomography.

Previously, rubidium-82 and positron emission tomography (PET) have been used to assess qualitatively the integrity of the blood-brain barrier (BBB). In this report, a method is described to measure the fractional extraction of rubidium across the BBB using the constant intravenous infusion of rubidium-82. In addition, the continuous inhalation of oxygen-15-labelled carbon dioxide is needed to measure regional CBF, and it is also necessary to measure regional cerebral blood volume. The assumptions underlying the model are identified, and the impact of deviations from these assumptions is described. From radiation dose and statistical considerations, it is shown that for normal cerebral tissue and the PET scanner used in this study, the rubidium extraction fraction can be quantitated only for regions as large as a cerebral hemisphere. However, quantitation is also possible for smaller regions where the focal extraction of rubidium is increased.

Blood-Brain Barrier↗
PubMed1983

Elemental analysis in murine central nervous system: elevation of rubidium subsequent to Newcastle disease virus encephalopathy.

The Cg strain of Newcastle disease virus (NDV) produces neurologic signs and death in mice. This illness is unusual because of the lack of typical features of a viral encephalitis. Specifically, there is a paucity of infectious virus, detectable cellular inflammatory reaction, cytopathic effect, and viral antigen by immunofluorescence. We previously showed an elevation of alpha-aminoisobutyric acid in the CNS of moribund NDV-infected mice, indicating cellular membrane dysfunction. In an attempt to further our understanding of the pathogenesis of the illness, we evaluated CNS concentrations of sodium, potassium, iron, copper, zinc, magnesium, selenium, and rubidium. Elemental analysis revealed no difference between infected and control mice for all elements except for rubidium, which was significantly elevated in infected mice. Elevation in rubidium was detected in infected mice by X-ray fluorescence and atomic absorption spectrophotometry, whereas rubidium concentrations for control mice were similar by both methods. Neurologic symptoms correlated directly with rising rubidium concentrations. Our data suggest that abnormal trace element levels during viral infection may be one mechanism responsible for the clinical symptoms.

Animals↗
PubMed2005

Observation of 1,6-anhydro-beta-maltose and 1,6-anhydro-beta-D-glucopyranose complexed with rubidium by NMR spectroscopy and electrospray ionization mass spectrometry.

A complex of 1,6-anhydro-beta-maltose with rubidium and that of 1,6-anhydro-beta-D-glucopyranose with rubidium were characterized using 87Rb NMR spectroscopy, diffusion-ordered NMR spectroscopy (DOSY) and electrospray ionization mass spectrometry (ESI-MS). Although subtle differences were observed in the 1H chemical shifts of 1,6-anhydro-beta-maltose in between the presence and absence of rubidium in deuterium oxide, measurements of the spin-lattice relaxation time (T1) of the 87Rb nucleus, the diffusion coefficients of 1,6-anhydro-beta-maltose using 1H DOSY and ESI-MS indicated the complex formation of 1,6-anhydro-beta-maltose with rubidium. The complex formation with rubidium was also identified for 1,6-anhydro-beta-D-glucopyranose using NMR and ESI-MS techniques.

Glucose↗
PubMed2001

Glucose-induced activation of rubidium transport and water flux in sunflower root systems.

Excised 20-d-old sunflower roots (Helianthus annuus L. cv. Sun-Gro 393) were used to study the effect of different sugars on rubidium and water fluxes. The roots sensed and absorbed glucose from the external medium inducing the activation of rubidium accumulated in the root (Rb(+) root), the flux of exuded rubidium (J(Rb)) and, to a lesser degree, the exudation rate (J(v)). These effects were also triggered by fructose, but not by 6-deoxyglucose (6-dG), a glucose analogue which is not a substrate for hexokinase (HXK). The effect of 2-deoxyglucose (2-dG), an analogue that is phosphorylated but not further metabolized, was complex, suggesting an inhibitory effect on solute transport to the xylem. The amounts of glucose required to activate rubidium and water fluxes were similar to those previously reported to regulate different processes in other plants (0.5--10 mM). When sorbitol was used instead of glucose, neither rubidium uptake (Rb(+) root plus J(Rb)) nor J(v) was activated. It is proposed that glucose present in the root plays an important signalling role in the regulation of Rb(+) (K(+)) and water transport in plant roots.

Carbon Radioisotopes↗
PubMed1990

Feasibility of measuring first pass extraction and flow with rubidium-82 in the kidneys.

A feasibility study has been carried out to evaluate rubidium-82, a potassium analog and generator-produced positron emitter, for measuring renal blood flow using a first pass model. Seven acute dogs were studied with beta probes and positron emission tomography to understand the dynamics of rubidium-82 in the kidneys. Preliminary results show that first pass extraction fraction for rubidium-82 ranged from 80-95% with an average of 89%. During the 150 sec of data collection, approximately 44.5% of the injected dose is excreted in the venous side and 9.75% in the ureter. Flow measurements with rubidium-82 and microspheres correlated well with the average control flow of 5.0 ml/min/gm measured by microspheres and 4.5 ml/min/gm of flow measured by rubidium-82 using the first pass model.

Animals↗
PubMed1989

Efflux of rubidium in rat cortical synaptosomes is blocked by sigma and dextromethorphan binding site ligands.

Large concentrations of potassium were used to stimulate the release of rubidium-86 from preloaded cortical synaptosomes, so that the pharmacological sensitivity of this efflux could be examined. Potassium channel blockers, 4-aminopyridine and tetraethylammonium, inhibited the evoked release of rubidium. Sigma ligands, e.g. pentazocine, cyclazocine, rimcazole, 1,3-di(2-tolyl)guanidine (DTG) and haloperidol, as well as the antitussives, carbetapentane, caramiphen and dextromethorphan, significantly reduced potassium-stimulated efflux of rubidium. By contrast, 3-hydroxyphenyl-propylpiperidine (3-PPP), 5-methyl-10,11-dihydro-5H-dibenzo(a,d)-cyclohepten-5,10-imine (MK-801), phencyclidine (PCP), ketamine and D-2-amino-5-phosphonovalerate (D-AP5) were all inactive. This suggests that inhibition of potassium-stimulated efflux of rubidium is correlated with activity at the sigma and/or dextromethorphan binding sites rather than at the N-methyl-D-aspartate (NMDA)/PCP receptor-channel complex.

Animals↗
PubMed1979

Influx theory and size of potassium and rubidium pools in the midgut of Hyalophora cecropia.

1. The midgut contains a 'pool' which must mix with tracer added to the blood-side, before the transported potassium reaches a steady specific activity. The size and mixing time of the pool can be deduced from the time-course of rate of appearance of tracer on the lumen-side, the tracer influx. The theory has been extended to cover cases where the pool-size and the transport rate vary with time. 2. By using 42K and 86Rb together, it is shown that the midgut treats potassium and rubidium differently, rubidium being transported nine-tenths as fast as potassium, when both are present in equal concentration. The influx pool for potassium is one-third larger than that for rubidium, but mixes four-fifths as fast with blood-side tracer. 3. The size of the potassium pool decreases with time, but that for rubidium does not, and the ratios of mixing times and transport rates are constant. 4. The implications of the results are discussed, both in terms of the accuracy of previous investigations and with respect to the probable intracellular location of part of the influx pool.

Animals↗
PubMed1991

A pharmacokinetic analysis of long-term administration of rubidium chloride.

When a substance with a long biologic half-life is administered over an extended period with a varying dose schedule, many concerns about safety arise. In the case of rubidium chloride, which has been reported to have antidepressive activity, some of these concerns are related to the potential for unanticipated accumulation in the intracellular fluid, where replacement of more than 40% of the potassium ions is associated with toxicity in animals. A pharmacokinetic model of rubidium distribution, based on a three-compartment system, is in accord with the empirical data from previous human trials. By comparison of predicted with observed plasma rubidium levels, a sudden change in the ratio of intra- to extracellular distribution of rubidium can be detected, and availability of this warning signal of potentially toxic intracellular accumulation can be useful during extended administration.

Animals↗
PubMed1999

Functional analysis of native and recombinant ion channels using a high-capacity nonradioactive rubidium efflux assay.

A nonradioactive cell-based rubidium (Rb(+)) efflux assay for functional analysis of native and recombinant ion channels has been developed. Cells are first loaded with rubidium, a tracer for potassium, and after channel activation, rubidium distribution between intracellular and extracellular space is determined by atomic absorption spectroscopy. The relative amount of rubidium in the cell supernatant is a direct measure of channel activity. The broad utility of the method is demonstrated by analysis of a range of different ion channels. Ligand-gated ion channels like nicotinic acetylcholine receptors and purinergic P2X receptors were studied in native PC-12 cells. Calcium-activated potassium channels were analyzed in native (small-conductance calcium-activated potassium channel, SK(Ca)) as well as recombinant cell lines (large-conductance calcium-activated potassium channel, BK(Ca)). Also recombinant voltage-gated potassium channels (Kv1.1, Kv1.4) were amenable to this functional analysis. The method is particularly useful for identification of ion channel modulators in drug discovery since it allows functional analysis with high capacity.

Animals↗
PubMed1979

[Influence of lithium and rubidium on exploratory behaviour and locomotor activity in isolated male mice (author's transl)].

The effect of lithium and rubidium on curiosity rearing, and locomotor activity in isolated and group-housed male mice (DBA/2 Han) was investigated. LiCl and RbCl were given with the drinking water (30 mol/l) during 3 weeks. The behaviour of the animals was tested before and after the chronical application of either lithium or rubidium. The results show that lithium was able to enhance the decreased curiosity of the isolated mice which now was no longer different from that of normal group-housed animals. The locomotor activity of the isolated animals was also increased by LiCl, while rearing was not altered. Rubidium even more decreased the already diminished curiosity of the 'fighting mice' but had no influence on rearing and locomotor activity. Three weeks after cessation of treatment the behaviour of the isolated mice returned to predrug levels. Neither lithium nor rubidium had any influence of the behaviour of animals kept in groups.

Animals↗
PubMed1988

An isotopic rubidium ion efflux assay for the functional characterization of nicotinic acetylcholine receptors on clonal cell lines.

An isotopic rubidium ion efflux assay has been developed for the functional characterization of nicotinic acetylcholine receptors on cultured neurons. This assay first involves the intracellular sequestration of isotopic potassium ion analog by the ouabain-sensitive action of a sodium-potassium ATPase. Subsequently, the release of isotopic rubidium ion through nicotinic acetylcholine receptor-coupled monovalent cation channels is activated by application of nicotinic agonists. Specificity of receptor-mediated efflux is demonstrated by its sensitivity to blockade by nicotinic, but not muscarinic, antagonists. The time course of agonist-mediated efflux, within the temporal limitations of the assay, indicates a slow inactivation of receptor function on prolonged exposure to agonist. Dose-response profiles (i) have characteristic shapes for different nicotinic agonists, (ii) are described by three operationally defined parameters, and (iii) reflect different affinities of agonists for binding sites that control receptor activation and functional inhibition. The rubidium ion efflux assay provides fewer hazards but greater sensitivity and resolution than isotopic sodium or rubidium ion influx assays for functional nicotinic receptors.

Animals↗
PubMed1981

Concentration differences between serum and plasma of the elements cobalt, iron, mercury, rubidium, selenium and zinc determined by neutron activation analysis.

The differences in concentrations of cesium, cobalt, iron, mercury, rubidium, selenium and zinc between serum and plasma were examined with the aid of instrumental neutron activation analysis. Eighty serum and plasma samples obtained from 13 donors were compared. Serum was prepared in plastic tubes immediately after clotting, and plasma was separated with heparin as anticoagulant. No significant differences in the concentrations of cesium, cobalt, mercury and selenium were observed. However, the concentrations of iron, rubidium and zinc were significantly higher in serum than in plasma. The average differences were 322, 12 and 20 ng/ml for iron rubidium and zinc, respectively. The average differences found for cesium, rubidium and zinc were far below that which can be expected from a complete, or considerable release of these elements from platelets which aggregate or disintegrate during the clotting process in preparing serum.

Cobalt↗
PubMed2005

Characterization of a hERG screen using the IonWorks HT: comparison to a hERG rubidium efflux screen.

The introduction of parallel patch clamp instruments offers the promise of moderate-throughput, high-fidelity voltage clamp for drug screening assays. One such device, the IonWorks HT (Molecular Devices, Sunnyvale, CA), was evaluated and compared to conventional human ethera- go-go-related gene (hERG) patch clamp data and an alternative functional screen based on rubidium flux. Data generated by the IonWorks HT and rubidium assays were compared to determine if either offered superior predictive value compared to conventional patch clamp. Concentration-effect curves for a panel of known hERG blockers were shifted to higher concentrations on the IonWorks HT compared to conventional voltage clamp determinations. The magnitude of the potency shifts was compound-specific and ranged from no shift (e.g., quinidine) to over 200-fold (astemizole). When the extreme value for astemizole was disregarded, the potency shift for 13 other known reference standards was 12-fold or less, with an average shift of fivefold. The same subset of compounds in the rubidium efflux assay exhibited an average potency shift of 12-fold. To provide a simulation of how the IonWorks HT assay might perform in a single concentration screening mode, a panel of test compounds was evaluated. The IonWorks HT screen did not outperform the rubidium efflux screen in predicting conventional voltage clamp measurements. The most likely explanation appears to rest with variable and compound-specific potency shifts in the IonWorks HT assay. The variable potency shifts make it difficult to select a screening concentration that meets the criterion of a high positive predictive value while avoiding false-positives.

Animals↗
PubMed2006

Evaluation of the rubidium efflux assay for preclinical identification of HERG blockade.

Inhibition of the delayed-rectifier potassium channel current, human ether-a-go-go (hERG), by pharmaceutical agents can lead to acquired long QT syndrome and the generation of potentially lethal arrhythmias and sudden death. There remains an unmet need for higher-throughput assays to screen compounds in preclinical development for the potential to block hERG and cause QT prolongation. We evaluated the rubidium efflux assay for its ability to determine block of the hERG potassium channel. hERG-transfected human embryonic kidney-293 cells were cultured on 96-well assay plates and loaded with rubidium ion by incubating in media in which potassium was replaced by 5.4 mM Rb+. Cells were exposed to test compounds and then depolarized with a K+ channel opening buffer containing 50 mM K+. The supernatant was removed, and cells were lysed using 0.1% Triton X-100. Concentration-response curves were generated for test agents by determining the Rb+ efflux using a flame atomic absorption spectrometer. Multiple trials with cisapride yielded 50% inhibitory concentration values between 308.1 +/- 11 nM to 456.3 +/- 24 nM for inhibition of Rb+ efflux and a Z factor of 0.80 +/- 0.07 (n = 5 plates, 12 wells per plate). The values for inhibition of the hERG channel exhibited a rightward shift in potency as compared to those measured using electrophysiological techniques. In addition, we evaluated 19 blinded compounds at 10 microM in the Rb+ efflux assay, and compared results to those using patch clamp electrophysiology and the dofetilide displacement binding assay. The dofetilide displacement binding assay yielded a good correlation with electrophysiological measurements of hERG block. The rubidium efflux assay lacked sensitivity to consistently identify significant channel blockade. In conclusion, the rubidium efflux assay provides a higher-throughput means to identify potent hERG channel blocking agents, but lacks the sensitivity required to accurately determine the potency of blockade.

Cell Line↗
PubMed2001

Using surface-bound rubidium ions for protein phasing.

Rubidium is a monovalent metal that can be used as a counterion in protein solutions. X-ray anomalous scattering from rubidium ions bound to the protein surface was used for phasing of the crystal structure of the hsp60 apical domain from Thermus thermophilus. Multiple-wavelength anomalous dispersion (MAD) data were collected from a crystal obtained from a solution containing 0.2 M rubidium salt. One molecule of protein (147 amino acids) binds one well ordered and one poorly ordered Rb atom. Phases calculated with the program SHARP were sufficient for automatic tracing and side-chain assignment using the program ARP/wARP. The data show that bound rubidium ions can be used to determine protein structures and to study the interaction of monovalent metal ions with proteins and other macromolecules.

Bacterial Proteins↗
PubMed1988

Selenium, rubidium and zinc in human semen and semen fractions.

The levels of selenium, rubidium and zinc were determined in samples of semen, seminal plasma and spermatozoa from men with suspected infertility, together with several parameters of semen quality. The proportion of whole semen selenium present in sperm increased with increasing sperm count from 0 to 40%. For rubidium 98 +/- 4% and for zinc 95 +/- 8% of the total amount in semen was contained in seminal plasma. In seminal plasma a positive correlation was found between the levels of zinc and selenium, and between the levels of zinc and rubidium, indicating that, like zinc, selenium and rubidium in seminal plasma also derive mainly from the prostate gland. Semen quality parameters, such as sperm motility, vitality, speed and morphology, were not correlated with the contents of the three elements in either whole semen or seminal plasma. As the seminal content of selenium is dependent on the proportion of prostatic secretion in seminal plasma and on the sperm count, and both factors can vary considerably, the selenium level of whole semen does not appear to be a suitable parameter for investigation of the relationship between selenium and semen quality. Provisional measurements suggest lower sperm selenium levels at abnormally low or high sperm counts.

Humans↗
PubMed1984

Characterization of contractions in enzymatically isolated rat ventricular myocytes: effects of ouabain and rubidium.

The role of sarcolemma and especially sodium pump activity in the control of phasic contractile activity of Ca2+ tolerant myocytes was studied using ouabain and rubidium as sodium pump inhibitors. Initially, ouabain increased both the amplitude of shortening and the frequency of phasic contractions. Later, the amplitude began to decline whereas the frequency of beating continued to rise, often terminating in a steady contracture of the myocyte. Rubidium caused a rapid rise of beating frequency, which reached its full effect within 1-5 min and remained steady after that. The stimulation of contraction frequency and the inhibition of Na+-K+ ATPase were correlated in the case of ouabain but not in the case of rubidium. The results suggest that the stimulation of phasic contractions may be caused by increased uptake of cellular calcium through Na+-Ca+ exchange as a consequence of sodium pump inhibition and (or) depolarization of the sarcolemma by ouabain and rubidium.

Animals↗