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The Journal of Biological Chemistry May 1985Since the mechanism underlying the insulin stimulation of (Na+,K+)-ATPase transport activity observed in multiple tissues has remained undetermined, we have examined... (Comparative Study)
Comparative Study Review
Since the mechanism underlying the insulin stimulation of (Na+,K+)-ATPase transport activity observed in multiple tissues has remained undetermined, we have examined (Na+,K+)-ATPase transport activity (ouabain-sensitive 86Rb+ uptake) and Na+/H+ exchange transport (amiloride-sensitive 22Na+ influx) in differentiated BC3H-1 cultured myocytes as a model of insulin action in muscle. The active uptake of 86Rb+ was sensitive to physiological insulin concentrations (1 nM), yielding a maximum increase of 60% without any change in 86Rb+ permeability. In order to determine the mechanism of insulin stimulation of (Na+,K+)-ATPase activity, we demonstrated that insulin also stimulates passive 22Na+ influx by Na+/H+ exchange transport (maximal 200% increase) and an 80% increase in intracellular Na+ concentration with an identical time course and dose-response curve as insulin-stimulated (Na+,K+)-ATPase transport activity. Incubation of the cells with high [Na+] (195 mM) significantly potentiated insulin stimulation of ouabain-inhibitable 86Rb+ uptake. The ionophore monensin, which also promotes passive Na+ entry into BC3H-1 cells, mimics the insulin stimulation of ouabain-inhibitable 86Rb+ uptake. In contrast, incubation with amiloride or low [Na+] (10 mM), both of which inhibit Na+/H+ exchange transport, abolished the insulin stimulation of (Na+,K+)-ATPase transport activity. Furthermore, each of these insulin-stimulated transport activities displayed a similar sensitivity to amiloride. These results indicate that insulin stimulates a large increase in Na+/H+ exchange transport and that the resulting Na+ influx increases the intracellular Na+ concentration, thus activating the internal Na+ transport sites of the (Na+,K+)-ATPase. This Na+ influx is, therefore, the mediator of the insulin-induced stimulation of membrane (Na+,K+)-ATPase transport activity classically observed in muscle.
Topics: Animals; Biological Transport, Active; Carrier Proteins; Cell Line; Insulin; Mice; Muscles; Rubidium; Sodium; Sodium-Hydrogen Exchangers; Sodium-Potassium-Exchanging ATPase
PubMed: 2987218
DOI: No ID Found -
The Journal of Physiology Jul 19801. A three-electrode voltage clamp method was used to investigate the Rb block of inward rectification in frog sartorius muscle fibres. 2. In a solution containing 80...
1. A three-electrode voltage clamp method was used to investigate the Rb block of inward rectification in frog sartorius muscle fibres. 2. In a solution containing 80 mM-K+, the potassium conductance increased with increasing hyperpolarization to 3.18 +/- 0.11 mS. cm-2 (n = 17) when (V - VK) was -150 mV. In the presence of Rb+, the conductance increased, fell and increased again with increasing hyperpolarization, i.e. the Rb block was first increased and then reduced by increasing hyperpolarization. Increasing [Rb]o increased the block at all voltages. 3. In a solution containing 80 mM-Rb+ (zero K+) inward currents were recorded when the membrane was hyperpolarized beyond about -60 mV. These currents, which were < 10% the amplitude of those in 80 mM-K solution, were blocked by tetraethylammonium ions. 4. Experiments were carried out in solutions either where both [K]o and [K]i were increased, or where [K]o only was increased. The form of the relation between K conductance and membrane potential appeared to depend on [K]o. The magnitude of the conductance appeared to depend on [K]o and on [K]i. 5. So far as the block by Rb+ is concerned, increasing [K]o appeared to enhance the release of Rb block under large hyperpolarizations. Increasing [K]o and [K]i reduced the Rb block at all membrane potentials. 6. The results of experiments in the presence of Rb+ and Cs+ suggest that these two ions do not compete with each other for a site at which they block inward rectification. Rather, over a range of membrane potentials from -25 to -65 mV, the presence of Cs+ enhances the Rb block and vice versa. 7. Single dissected muscle fibres (from semitendinosus) were used to measure sarcoplasmic resistivity in 80 mM-K solution and 160 mM-K (hyperosmotic) solution. The measured values were 163.2 +/- 11.7 omega x cm and 136.1 +/- 16.0 omega x cm, respectively (n = 7). 8. A semi-empirical model is presented, supposing that Rb interacts with a site in the membrane to produce its blocking effect, but is able to move on through into the sarcoplasm. Internal K+ is supposed to reduce the affinity of the site for Rb+; external K+ is able to enhance the moving on of Rb+ into the sarcoplasm. 9. The implications of our experiments for the nature of the permeability mechanism inward rectification are discussed.
Topics: Animals; Cesium; Electric Conductivity; In Vitro Techniques; Membrane Potentials; Muscles; Potassium; Ranidae; Rubidium; Sarcoplasmic Reticulum; Tetraethylammonium Compounds
PubMed: 7441543
DOI: 10.1113/jphysiol.1980.sp013333 -
Brain and Behavior Mar 2019The applicability of "Rubidium Chloride, Rb from Generator" radiopharmaceutical for brain tumors (BT) diagnostics is demonstrated on the basis of the application...
INTRODUCTION
The applicability of "Rubidium Chloride, Rb from Generator" radiopharmaceutical for brain tumors (BT) diagnostics is demonstrated on the basis of the application experience of the radiopharmaceutical in neurooncology.
EXPERIMENTAL
A total of 21 patients with various brain tumors and nonneoplastic abnormal brain masses were investigated.
RESULTS AND DISCUSSIONS
The results of the imaging and differential diagnostics of malignant and benign tumors, nonneoplastic abnormal brain masses and lesions revealed the prevalence of high uptake of the radiopharmaceutical in the malignant tumors in comparison with benign glioma and arteriovenous malformations in which Rb-chloride accumulates in the vascular phase but does not linger further. The ultra-short half-life of radionuclide Rb (76 s) along with a low absorbed radiation dose with Rb-chloride by intravenous administration create a new possibility of successive use of two or more radiopharmaceuticals for the examination of the same patient. For instance, PET examination with F-FDG, C-methionine, C-choline, or any other radiopharmaceutical can be carried out in just 7-15 min. after Rb-chloride injection.
CONCLUSION
Research demonstrated an effectiveness of Rb-chloride application as a diagnostic agent in neurooncology. A method of dosing and administration of the generator-produced radiopharmaceutical has been worked out. It is possible to do up to 600 PET sessions using one Russian Rb generator GR-01. The generator is proved to be reliable and easy to use. The interest in Rb-chloride as a tumor-seeking radiopharmaceutical rose due to the active application of the modern devices PET/CT in the routine clinical practice.
Topics: Brain; Brain Neoplasms; Chlorides; Diagnosis, Differential; Humans; Medical Oncology; Positron Emission Tomography Computed Tomography; Radiopharmaceuticals; Rubidium; Strontium Radioisotopes
PubMed: 30729720
DOI: 10.1002/brb3.1212 -
ChemMedChem Nov 2021Triple negative breast cancer (TNBC) is one of the breast cancers with poorer prognosis and survival rates. TNBC has a disproportionally high incidence and mortality in...
Triple negative breast cancer (TNBC) is one of the breast cancers with poorer prognosis and survival rates. TNBC has a disproportionally high incidence and mortality in women of African descent. We report on the evaluation of Ru-IM (1), a water-soluble organometallic ruthenium compound, in TNBC cell lines derived from patients of European (MDA-MB-231) and African (HCC-1806) ancestry (including IC values, cellular and organelle uptake, cell death pathways, cell cycle, effects on migration, invasion, and angiogenesis, a preliminary proteomic analysis, and an NCI 60 cell-line panel screen). 1 was previously found highly efficacious in MDA-MB-231 cells and xenografts, with little systemic toxicity and preferential accumulation in the tumor. We observe a similar profile for this compound in the two cell lines studied, which includes high cytotoxicity, apoptotic behavior and potential antimetastatic and antiangiogenic properties. Cytokine M-CSF, involved in the PI3/AKT pathway, shows protein expression inhibition with exposure to 1. We also demonstrate a p53 independent mechanism of action.
Topics: Antineoplastic Agents; Cell Cycle; Cell Death; Cell Line, Tumor; Cell Movement; Cell Proliferation; Coordination Complexes; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Humans; Imines; Molecular Structure; Phosphoranes; Rubidium; Structure-Activity Relationship; Triple Negative Breast Neoplasms
PubMed: 34329530
DOI: 10.1002/cmdc.202100325 -
Quarterly Journal of Experimental... Apr 1986The efflux of 42K+ and 86Rb+ has been studied in collagenase-isolated normal mouse islets of Langerhans. In double-labelled experiments, the ratio of efflux rate...
The efflux of 42K+ and 86Rb+ has been studied in collagenase-isolated normal mouse islets of Langerhans. In double-labelled experiments, the ratio of efflux rate constants of Rb+ and K+ (kRb/kK) was 0.80 in 5 mM-K+ and 0 glucose. The ratio was unaffected by glucose concentrations up to 22.2 mM. In the presence of 50 mM-K+, 0 glucose, the ratio increased to 0.91 and in 50 mM-Rb+, 0 glucose and 0 K+, the ratio was 1.06. With these limitations, the results indicate that 86Rb+ is an acceptable isotope for K+. Using the Goldman model, K+ and Rb+ permeability coefficients and K+ slope and chord conductances were computed. The permeabilities decreased in glucose and in high K+ or high Rb+. In the case of high external K+, the K+ conductances increased. Also there may be more than one type of K+ channel with differing selectivities to K+ and Rb+. The addition of glucose in the presence of 50 mM-K+ had no further effect on Rb+ permeability. It is suggested that there are about ten small K+ channels open in the resting beta-cell and that progressive closure of these channels is involved in the depolarization of the cell membrane that initiates spike activity.
Topics: Animals; Cell Membrane Permeability; Electric Conductivity; Glucose; Islets of Langerhans; Mice; Osmolar Concentration; Potassium; Potassium Radioisotopes; Radioisotopes; Rubidium
PubMed: 3520625
DOI: 10.1113/expphysiol.1986.sp002979 -
The Journal of Physiology Nov 1985When Na,K-ATPase containing occluded rubidium ions is exposed to orthophosphate, in the presence of magnesium ions, there is a rapid release of half or all of the...
When Na,K-ATPase containing occluded rubidium ions is exposed to orthophosphate, in the presence of magnesium ions, there is a rapid release of half or all of the occluded ions. This behaviour is observed irrespective of whether the occluded-rubidium form of the enzyme is generated by putting the unphosphorylated enzyme in a sodium-free medium containing rubidium ions, or by allowing rubidium ions to catalyse the hydrolysis of phosphoenzyme made by adding ATP to enzyme suspended in a medium containing sodium and magnesium ions. The release of occluded rubidium ions by orthophosphate requires the presence of magnesium, presumably because phosphorylation is necessary. Whether the addition of orthophosphate causes the rapid release of all or of half of the occluded rubidium depends on whether free rubidium (or potassium, thallium or (probably) caesium ions) are present in the medium at the time the orthophosphate is added. In the absence of free ions of these species, all of the occluded rubidium is released. In their presence (in adequate concentration), only half of the occluded rubidium is released. The relative effectiveness of the different potassium congeners in preventing the rapid release of 50% of the occluded rubidium when orthophosphate is added is: thallium greater than rubidium greater than potassium greater than caesium. Lithium and sodium are ineffective even at high concentrations, and sodium ions strongly antagonize the effect of free rubidium ions. In a sodium-free, Tris medium, the concentration of free rubidium ions necessary for a half-maximal effect is about 30 microM. In a medium containing 250 microM-free rubidium, the concentration of sodium necessary to reduce the effect of free rubidium by 50% is about 500 microM. These figures are compatible with the hypothesis that the free rubidium or other ions act at the potassium-loading sites at the extracellular face of the pump. By starting with enzyme occluding unlabelled rubidium, and using 86Rb-labelled free rubidium, it is possible to show that the free ions that prevent the rapid release of half of the occluded ions themselves become occluded. These experiments are significant in two ways. First, they provide direct evidence for the existence of a second route for the release of occluded rubidium (and therefore presumably of occluded potassium) ions. Secondly, they seem to require that the release of occluded ions by this route occurs in an ordered fashion.
Topics: Animals; Cesium; Dogs; In Vitro Techniques; Kidney; Magnesium; Phosphates; Potassium; Rubidium; Sodium; Sodium-Potassium-Exchanging ATPase; Swine; Thallium
PubMed: 3001296
DOI: 10.1113/jphysiol.1985.sp015868 -
Journal of Nuclear Medicine : Official... Jun 1987Positron emission tomography (PET) with rubidium-82 (82Rb) has been developed to measure regional myocardial perfusion and to detect transient ischemia both in the...
Positron emission tomography (PET) with rubidium-82 (82Rb) has been developed to measure regional myocardial perfusion and to detect transient ischemia both in the experimental laboratory and in humans. There are known and separate contaminating effects of the 82Rb signal by disturbances in wall motion, wall thinning, and the partial volume effect that occur during transient ischemia. In nine anesthetized greyhounds, PET with 82Rb (T1/2 = 78 sec) was used to determine the regional myocardial uptake of this cation during a control period that consisted of a mild stenosis of the left anterior descending coronary artery in the absence of ischemia (to limit reactive hyperemia), during 10 min of total occlusion and, finally, at 30 and 60 min of recovery with release of the occlusion but not of the stenosis. Separately, rubidium-81 (81Rb); T1/2 = 4.58 hr) was given as a peripheral intravenous injection 2 hr before the study to allow this long-lived tracer to distribute in the potassium space of the myocardium. Observations during control and ischemia revealed marked decreases in 82Rb uptake (0.84 +/- 0.12 to 0.28 +/- 0.12, p = 0.001) in affected regions and were paralleled by similar decreases in microsphere blood flow (0.88 +/- 0.08 to 0.12 +/- 0.10 ml/min/g, p = 0.003), which gradually recovered by 60 min postischemia. Lesser decreases in 81Rb activity (0.84 +/- 0.11 to 0.76 +/- 0.17, p = 0.83) were observed in the same regions during ischemia, but these were immediately reversible. Separate in vitro postmortem experiments in eight rabbits confirmed a linear relationship between plasma and myocardial activities of stable potassium and 81Rb although there was a greater concentration of 81Rb in the myocardium that in the plasma relative to potassium (y = -3.29 +/- 0.79 x, s.e.e. 1.91, r = 0.95). These studies demonstrate that if 81Rb is given intravenously to distribute into the potassium pool, tomograms of the heart may be recorded to measure the potassium-rich mass of myocardium providing information about the acute effects of wall thinning during ischemia. Rubidium-81 used in this way may be helpful in assessing the effects of wall thinning and/or scar when other tracers are being used to assess perfusion or metabolism.
Topics: Animals; Coronary Disease; Dogs; Rabbits; Radioisotopes; Rubidium; Time Factors; Tomography, Emission-Computed
PubMed: 3495648
DOI: No ID Found -
The Journal of Clinical Investigation Apr 1985Currently available noninvasive techniques are unable to rapidly assess artery patency and tissue viability during acute myocardial infarction. In prior studies,...
Currently available noninvasive techniques are unable to rapidly assess artery patency and tissue viability during acute myocardial infarction. In prior studies, rubidium-82 (Rb-82), a short-lived positron emitter obtained from a generator, was validated as an indicator of flow with a model that included the rate constants for transfer into and out of the cell. Accordingly, in the current study, 20 open-chested dogs with experimental infarction were studied serially at base line, after coronary occlusion, and at reperfusion. Time-activity curves acquired with beta probes on the epicardial surface were used to measure flow and net transfer of rubidium. Flow decreased to 0.41 +/- 0.08 ml/min per gram during occlusion and increased to 2.73 +/- 0.56 ml/min per gram in potentially viable ischemic tissue, whereas flows were 0.32 +/- 0.08 during occlusion (P less than 0.05 vs. viable) and 1.58 ml/min per gram (P less than 0.002 vs. viable) in irreversibly injured tissue. The transfer rate constant for Rb-82, kT, at base line was +1.22 +/- 0.60 X 10(-3) s-1 and did not change significantly during occlusion in viable vs. nonviable samples (+1.41 +/- 1.27 vs. +0.93 +/- 1.51 X 10(-3) s-1, respectively), except that 4 out of 11 nonviable tissue samples had negative kTs. At reperfusion, viable myocardial samples were all positive (+1.26 +/- 1.58 X 10(-3) s-1), whereas all irreversibly injured tissues had a negative kT, indicating leakage of tracer (-1.50 +/- 1.10 X 10(-3) s-1, P less than 0.001). This study suggests that Rb-82 time-activity curves can be useful to determine patency of an infarct related artery and potential viability after reperfusion during myocardial infarction.
Topics: Animals; Coronary Circulation; Coronary Disease; Dogs; Kinetics; Perfusion; Radioisotopes; Rubidium
PubMed: 3988934
DOI: 10.1172/JCI111807 -
The Journal of General Physiology Nov 1958Potassium-free artificial sea water causes a loss of cell potassium and a gain of cell sodium in Porphyra perforata, which is not attributable to an inhibition of...
Potassium-free artificial sea water causes a loss of cell potassium and a gain of cell sodium in Porphyra perforata, which is not attributable to an inhibition of respiration. On adding KCl or RbCl to such low potassium, high sodium tissues, net accumulation of potassium or rubidium takes place, accompanied by net extrusion of sodium. Rates of potassium or rubidium accumulation and sodium extrusion are proportional to the amount of KCl or RbCl added only at low concentrations. Saturation of rates is evident at KCl or RbCl concentrations above 20-30 mM, suggesting the role of an ion carrier mechanism of transport. Evidence for and against mutually dependent sodium extrusion and potassium or rubidium accumulation is discussed.
Topics: Eukaryota; Ions; Porphyra; Potassium; Rubidium; Sodium
PubMed: 13587912
DOI: 10.1085/jgp.42.2.281 -
Journal of Nuclear Medicine : Official... May 1987The comparative effects of altered cellular function and coronary perfusion on myocardial 201Tl and 83Rb uptake were evaluated in three groups of isolated rabbit hearts...
The comparative effects of altered cellular function and coronary perfusion on myocardial 201Tl and 83Rb uptake were evaluated in three groups of isolated rabbit hearts having isovolumic contractions. Paired-indication dilution experiments were performed with 201Tl, 83Rb, and 111In-labeled albumin as an intravascular reference marker. In Group A hearts (n = 12), isotope transport was determined during control, hypoxia, and ischemia. In Group B hearts (n = 8), isotope transport was measured at control flow and again at a 50% and 80% reduction. In Group C hearts (n = 8) only 201Tl uptake was determined at control and following coronary reperfusion. Myocardial 201Tl and 83Rb transport were not significantly different and were proportional to flow. Although all interventions caused significant hemodynamic alterations, neither tracer was affected by hypoxia at constant flow. Thallium-201 permeation, however, was transiently decreased immediately after coronary reperfusion. We conclude that myocardial uptake of 201Tl and 83Rb are similar and directly related to flow, but do not reflect hypoxia induced cellular dysfunction.
Topics: Animals; Coronary Circulation; In Vitro Techniques; Myocardium; Oxygen; Rabbits; Radioisotopes; Rubidium; Thallium
PubMed: 3572547
DOI: No ID Found