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1.
Abstract

The effect of Li+, Rb+ and tetraethylammoniumchloride (TEA) on the locomotor activity rhythm of Musca domestica was studied. Li+ as well as TEA lengthen the free run period t. This effect was more pronounced in animals with shorter period lengths. The effect of Rb? depends on the previous period length. In flies which had a short period, Rb+ lengthened, and in those with a long period Rb+ shortened t. Replacing the Li+ solution with water reverted the period lengthening partly. In the case of Rb? and TEA the rhythm became obscured after replacing the solutions with water. The involvement of K+ ions and transport ATPases in the expression of circadian rhythms is discussed.  相似文献   

2.
Background Exposing eukaryotic cells to lithium ions (Li+) during development has marked effects on cell fate and organization. The phenotypic consequences of Li+ treatment on Xenopus embryos and sporulating Dictyostelium are similar to the effects of inhibition or disruption, respectively, of a highly conserved protein serine/threonine kinase, glycogen synthase kinase-3 (GSK-3). In Drosophila, the GSK-3 homologue is encoded by zw3sgg, a segment-polarity gene involved in embryogenesis that acts downstream of wg. In higher eukaryotes, GSK-3 has been implicated in signal transduction pathways downstream of phosphoinositide 3-kinase and mitogen-activated protein kinases.Results We investigated the effect of Li+ on the activity of the GSK-3 family. At physiological doses, Li+ inhibits the activity of human GSK-3β and Drosophila Zw3Sgg, but has no effect on other protein kinases. The effect of Li+ on GSK-3 is reversible in vitro. Treatment of cells with Li+ inhibits GSK-3-dependent phosphorylation of the microtubule-associated protein Tau. Li+ treatment of Drosophila S2 cells and rat PC12 cells induces accumulation of cytoplasmic Armadillo/β-catenin, demonstrating that Li+ can mimic Wingless signalling in intact cells, consistent with its inhibition of GSK-3.Conclusions Li+ acts as a specific inhibitor of the GSK-3 family of protein kinases in vitro and in intact cells, and mimics Wingless signalling. This reveals a possible molecular mechanism of Li+ action on development and differentiation.  相似文献   

3.
The influence of alkali ions on the circadian leaf movements of Oxalis regnellii Mig. was investigated. Ions were given to the oscillating system via the transpiration stream of cut stalks in nutrient medium. Chloride solutions of Rb+, Cs+, Na+ and K+ were tested and the results compared to previously published LiCl-results. The period of the circadian leaf movements was unaffected by a continual addition of Na+ or K+ to the nutrient medium (at least up to 40 mM). Rb+, in the concentration of 2.5 or 5 mM, caused a shortening of the period when applied continuously. Rb+ concentrations up to 60 mM were tested. Cs+ ions caused only lengthenings of the circadian period. Cs+ concentrations up to 40 mM were tested. Cs+ resembled Li+ in producing period lengthenings, but was not as effective as Li+ when compared on a concentration basis. Toxicity of the effective ions was in the following order: Li+Cs+Rb+, Rb+ pulses (50 mM, 4 h) phase-shifted the rhythm and caused advances. A phase response curve was determined and the maximum steady state advances were of the order of 1 h. The dual effect of the Rb+ ions is discussed and is assumed to be due to two counteracting processes, exemplified by Rb+-sensitive ATPase-controlled pumping processes and protein synthesis. For comparison, the effects of Rb+ and Li+ in human depressive disorders is also discussed in relation to their influence on circadian systems. It is emphasized that Rb+ and K+ behave differently and are not interchangeable in their action on circadian systems.  相似文献   

4.
Kondo T 《Plant physiology》1984,75(4):1071-1074
The effect of Li+ on the period of the K+ uptake rhythm in the flow medium culture of the duckweed (Lemna gibba G3) was investigated under various ionic conditions. In the presence of Li+ at 0.2 millimolar or higher concentrations, the period was longer than the normal level of 25.4 hours by 2 hours. Li+ also lowered the amplitude of the rhythm. Although Na+ itself did not change any parameter of the rhythm, simultaneous application of Na+ at a very low concentration (20 micromolar) almost completely removed the effects of 0.5 millimolar Li+ on both the period and the amplitude. However, divalent cations (Ca2+ and Mg2+) or Rb+ did not remove the Li+ action on the period. The effect of Li+ and its removal by Na+ corresponded to intracellular Li+ and Na+ levels. The period was prolonged when the duckweed contained more Li+ than 5 micromoles/gram fresh weight. But the Li+ effect was cancelled when the in vivo Na+ level was greater than one-fifth that of Li+, even if the Li+ level exceeded over 5 micromoles/gram fresh weight.  相似文献   

5.
The period (~3-5 min) of the ultradian rhythm of the lateral leaflet movement of Desmodium motorium is strongly lengthened (≤30-40%) by the K+ channel blocker tetraethylammoniumchloride (20, 30, and 40 mM) and vanadate (0.5 and 1 mM), which is an effective inhibitor of the plasma membrane-bound H+ pump. The alkali ions K+, Na+, Rb+, and Cs+ (10-40 mM) shorten the period only slightly (≤ 10–15%). Li+ (5-30 mM), however, increases the period of the leaflet rhythm drastically (≤80%). We concluded that the plasmalemma-H+-ATP-ase-driven K+ transport through K+ channels is an essential component of the ultradian oscillator of Desmodium, as has been proposed for the circadian oscillator.  相似文献   

6.
Transport Pathways for Therapeutic Concentrations of Lithium in Rat Liver   总被引:1,自引:0,他引:1  
Although both amiloride- and phloretin-sensitive Na+/Li+ exchange activities have been reported in mammalian red blood cells, it is still unclear whether or not the two are mediated by the same pathway. Also, little is known about the relative contribution of these transport mechanisms to the entry of therapeutic concentrations of Li+ (0.2–2 mm) into cells other than erythrocytes. Here, we describe characteristics of these transport systems in rat isolated hepatocytes in suspension. Uptake of Li+ by hepatocytes, preloaded with Na+ and incubated in the presence of ouabain and bumetanide, comprised three components. (a) An amiloride-sensitive component, with apparent K m 1.2 mm Li+, V max 40 μmol · (kg dry wt · min)−1, showed increased activity at low intracellular pH. The relationship of this component to the concentration of intracellular H+ was curvilinear suggesting a modifier role of [H+] i . This system persisted in Na+-depleted cells, although with apparent K m 3.8 mm. (b) A phloretin-sensitive component, with K m 1.2 mm, V max 21 μmol · (kg · min)−1, was unaffected by pH but was inactive in Na+-depleted cells. Phloretin inhibited Li+ uptake and Na+ efflux in parallel. (c) A residual uptake increased linearly with the external Li+ concentration and represented an increasing proportion of the total uptake. The results strongly suggest that the amiloride-sensitive and the phloretin-sensitive Li+ uptake in rat liver are mediated by two separate pathways which can be distinguished by their sensitivity to inhibitors and intracellular [H+]. Received: 8 April 1999/Revised: 19 July 1999  相似文献   

7.
The influence of lithium on cell growth and cell viability was studied in short-term cultures of a neural precursor cell line (NT) developed from a murine teratocarcinoma. At very low concentrations ranging from 0.1 m to 1 m Li2CO3(equivalent to therapeutic blood concentrations) there was no difference between untreated and treated cultures. 10 m lithium (Li+) was found to be toxic with 33% of cell death, while there was inhibition of growth without cell death at concentrations of 2.5 m and 5 m of Li+. In experiments where 2.5 m Li+was added at the time of seeding, there was growth arrest on day 1 followed by recovery on day 2. Flow cytometric analysis revealed that cells treated with Li+were blocked in S phase. At 5 m concentration of Li+, the recovery occurred on day 3 and the plating efficiency was significantly low. The ability to form colonies in soft agar was reduced at 2.5 m and 5 m concentrations of Li+to an equal extent. Thus, Li+has growth inhibitory as well as anchorage-independent growth reducing effects. The NT cell line therefore would be a good model system to study the mechanism of teratogenic effect of Li+.  相似文献   

8.
Summary Ouabain-resistant Na+–Li+ countertransport was studied on erythrocytes of man, sheep, rabbit, and beef. A transport system, exchanging Li+ for Na+ in a ratio of 11, was present in all four species. Li+ uptake by the exchange system increased 30-fold in the order man +–Na+ exchange in these species, but bears no relation to the Na+–K+ pump activity. The activity of the Na+–Li+ exchange system varied up to 7 and 16-fold among individual red cell specimens from man and beef, the variability being much smaller in sheep and rabbit erythrocytes. The affinities of the system for Li+ and Na+ were similar among the species and individuals (half saturation of the external site at about 1mm Li+ and 50mm Na+, respectively).50–60% of Na+–Li+ exchange was blocked by N-ethylmaleimide in all species.p-Chloromercuribenzene sulfonate inhibited the exchange only in beef and sheep erythrocytes (60–80%). The two SH-reagents act by decreasing the maximum activity of the system, whilst leaving its affinity for Li+ unaltered. Phloretin was a potent inhibitor in all species. 1mm each of furosemide, ethacrynic acid, and quinidine induced only a slight inhibition. The Na+–Li+ exchange of human and beef erythrocytes increased 3.5-fold upon elevation of the extracellular pH from 6 to 8.5, the pH-dependence arising from a change in affinity of the system for the cations and being similar to that reported for ouabain-resistant Na+–Na+ exchange in beef erythrocytes.It is concluded that a transport system exists in the red cell membranes of the four species which can mediate ouabain-resistant exchange of either Na+ for Na+, Na+ for Li+, or Li+ for Li+. The exchange system exhibits essentially identical transport characteristics in the four species, but shows a marked inter- and intra-species variability in maximum transport capacity and some differences in susceptibility towards inhibitors. A similar transport system is probably present also in other tissues. The exchange system seems to be distinct from the conventional Na+–K+ pump and shows no clear relation to one of the furosemide-sensitive, ouabain-resistant Na+ transport systems described in the literature.  相似文献   

9.
Abstract: Rats were given LiCl in their diet (40 mmol/kg dry weight) for at least 3 months to elucidate the regional and subcellular localization of Li+ in the brain as well as the effect of chronic lithium administration on the distribution of other cations. At steady-state the mean concentrations of Li+ were 0.66 mmol/kg wet weight in the whole brain and 0.52 mM in plasma. The tissue/plasma concentration ratio exceeded unity in all anatomical regions. No region showed excessive accumulation of Li+. Whole brain or regional contents of Na+ or K+ were unaffected by lithium treatment. Subcellular Li+ localization was demonstrated in nuclear, crude mitochondrial, and microsomal fractions of whole brain homogenate. Subfractionation of the crude mitochondrial fraction revealed energy-independent intrasynaptosomal and intramitochondrial Li+ and K+ localization at 0–4°C. Li+ administered in vivo disappeared within 10 min from synaptosomes incubated at 37°C. Li+ added in vitro at 1 mM attained a synaptosomal steady-state concentration within 30 min at 37°C. In control rats, synaptosomal concentrations and synaptosomal/medium concentration gradients of cations paralleled their respective in vivo concentrations and gradients. Lithium treatment caused synaptosomal depletion of K+ and Mg2+ and hence probably partial membrane depolarization. Addition of 1 mM Li+ in vitro also caused synaptosomal Mg2+ depletion. The results indicate that Li+ is “accumulated” in brain sediments and synaptosomes following its long-term treatment. The estimated intracellular and intrasynaptosomal Li+ concentrations are lower than predicted by passive distribution according to the Nernst equation, evidencing active extrusion of Li+.  相似文献   

10.
Lithium salts with low coordinating anions such as bis(trifluoromethanesulfonyl)imide (TFSI) have been the state-of-the-art for polyethylene oxide (PEO)-based “dry” polymer electrolytes for 3 decades. Plasticizing PEO with TFSI-based ionic liquids (ILs) to form ternary solid polymer electrolytes (TSPEs) increases conductivity and Li+ diffusivity. However, the Li+ transport mechanism is unaffected compared to their “dry” counterparts and is essentially coupled to the dynamics of the polymer host matrix, which limits Li+ transport improvement. Thus, a paradigm shift is hereby suggested: the utilization of more coordinating anions such as trifluoromethanesulfonyl-N-cyanoamide (TFSAM), able to compete with PEO for Li+ solvation, to accelerate the Li+ transport and reach a higher Li+ transference number. The Li–TFSAM interaction in binary and ternary TFSAM-based electrolytes is probed by experimental methods and discussed in the context of recent computational results. In PEO-based TSPEs, TFSAM drastically accelerates the Li+ transport (increases Li+ transference number by a factor 6 and the Li+ conductivity by 2–3) and computer simulations reveal that lithium dynamics are effectively re-coupled from polymer to anion dynamics. Last, this concept of coordinating anions in TSPEs is successfully applied in LFP||Li metal cells leading to enhanced capacity retention (86% after 300 cycles) and an improved rate performance at 2C.  相似文献   

11.
—Rat cerebral slices were incubated in oxygenated Krebs-Ringer bicarbonate glucose saline, and the uptake of Li+ was measured after periods of 15 s to 5 min. Saturation was not seen within the concentrations of Li+ employed (0·5-2·0 mm ). The half-time of the uptake was 7·9 min. At steady state, after 1 h incubation, the concentration of Li+ in the tissue was linearly related to that of the medium (0·5-1·5 mm Li+) with a concentration ratio of 1·29–1·66. The concentrations of K+ and Na+ in the slices incubated without Li+ were found to be (μmol/g incubated wt, mean ±s.d .) 63·8 ± 9·6 and 96·2 ± 7·8 respectively (n = 28). In the presence of media with 1·5 mm -Li+, the K+ and Na+ in the slices were 56·2 ± 8·8 and 101·0 ± 7·7 respectively (n = 37). The concentration of Li+ in the slices, after 1 h incubation, increased in a non linear way as the concentration of K+ in the medium was decreased within a range of 0·10 mm -K+. In the absence of K+ in the medium the uptake of Li+ was approx 50% higher than in the presence of 4·9 mm -K+. There was an inverse linear relationship between the concentration of Li+ in the slices and that of Ca2+ in the medium within the range of 0-5·2 mm (-0·13 mm -Li+/mm Ca2+). The concentration of Li+ in the slices increased by approx 10% when the Mg2+ in the medium was increased from 1·3 mm to 2·6 mm . Changes of the concentration of Na+ between 120 mm and 170 mm in the medium had no significant effect on the Li+ uptake.  相似文献   

12.
Chronic treatment of rats with LiCl is known to induce a decrease in cAMP, while this decrease has also been found to occur together with both a simultaneous increase in total cortical phosphodiesterase (PDE; EC 3.1.4.17) activity and a concomitant increase in cGMP. These studies have implicated an involvement of PDE in lithium (Li+) action and it has been suggested that cGMP and the cGMP-stimulated PDE may be instrumental in the observed effects of Li+ on cAMP. In this study, three isozymes of PDE were isolated and identified from rat cortex and their activity determined, together with simultaneous measurement of cAMP and cGMP, after chronic treatment with oral LiCl (0.35% m/m). Li+ treatment exerted profound effects on cyclic nucleotides in the cortex, inducing significant suppression of cAMP while increasing cGMP levels. However, the ion only induced a slight but insignificant increase in the activities of the three PDE isozymes. To confirm these observations, methylparaben (MPB), a drug demonstrating both an ability to induce a selective stimulation of cAMP-specific PDE and also to lower intracellular levels of cGMP, was co-administration orally (0.4% m/m) with Li+ over the same period. This combination emphasized certain actions of Li+ not noted with Li+ alone. MPB inhibited the Li+-induced increase in cGMP, yet did not prevent the ion from decreasing cAMP. However, the combination of Li+ and MPB engendered a synergistic 100% increase in the activity of the membrane-bound, cAMP-specific PDE, PDE IV. This combination also produced a significant suppression of cAMP, while no reduction in cGMP was observed. The data is indicative that Li+-induced suppression of cAMP does not appear to be related to an effect on the cGMP-dependent PDE II, and that the increases in cGMP and PDE induced by Li+ observed previously and in the present study are two unrelated events. Instead, the synergistic response of Li+ plus MPB on PDE IV, and the associated reduction of cAMP, indicate that Li+ may promote selective cAMP hydrolysis via an effect on membrane-bound forms of PDE. This effect of Li+ on PDE IV, as well as the reciprocal effects on cyclic nucleotide balance, may have important implications in explaining the antipsychotic actions of the ion.  相似文献   

13.
Abstract

A selective metalation at the 6-CH3 over C-8 of 6-methylpurine derivative 6 was observed with softer counter cation (Na+ or K+) of the base, while the harder Li+ showed no selectivity. In the presence of N-fluorobenzenesulfonamide (NFSI), this property was utilized for the synthesis of 6-fluoromethylpurine derivatives 4 and 5 as potential toxins for suicide gene therapy.  相似文献   

14.
Summary The effects of prolonged cold exposure of Syrian hamsters on liver membrane (Na+/K+-ATPase activity and on liver intracellular K+ levels was examined. Membrane preparations from cold-acclimated hamsters (6°C for 3 weeks) exhibited significantly higherV max values for (Na+/K+)-ATPase and significantly greater ouabain binding. These data support the view that in the liver of these cold-exposed hamsters, there is an increase in the number of operational pumps. The fact that the intact liver cells (isolated via liver perfusion) from the cold-acclimated hamsters: (a) did not have higher concentrations of intracellular K+ (despite the presence of more operational pumps); and (b) exhibited greater rates of K+ loss when the pumps were inhibited by maximal ouabain suggests that the K+ leak across the liver cell plasma membrane is increased in the cold-acclimated hamsters. Although the physiological significance of these results needs further evaluation, these membrane changes may be of adaptive value for hibernation.Abbreviations CA cold-acclimated - P i inorganic phosphate - KRB Krebs-Ringer-bicarbonate buffer - BSA bovine serum albumin - ECF extracellular fluid - ICF intracellular fluid - dcs dry cell solid - N nitrogen  相似文献   

15.
Na+/H+ antiporter activity is wide-spread and plays essential physiological roles. We found that several Enterobacteriaceae share conserved sequences with nhaA, the gene coding for an E. coli antiporter. A nhaA strain which is sensitive to Na+ and Li+, was used to clone by complementation a DNA fragment from Salmonella enteritidis which confers resistance to the ions. The cloned fragment increased Na+/H+ antiport activity in membranes isolated from strains carrying the respective hybrid plasmid. DNA sequence analysis of the insert revealed two open reading frames. Both encode putative polypeptides which are closely homologous to the nhaA and nhaR gene products from Escherichia coli. The antiporter activity displays properties very similar to that of the E. coli NhaA, namely, it is activiated by alkaline pH and recognizes Li+ with high affinity.Abbreviations H + Proton electrochemical potential - pH transmembrane pH gradient - Na + Sodium electrochemical potential - SDS Sodium dodecyl sulfate - CIP Calf intestine alkaline phosphates - ORF open reading frame  相似文献   

16.
In Aspergillus niger Van Tieghem cultivated on a synthetic medium, the induction of an endogenous rhythm of sporulation and its perpetuation depend on the glucose K+ balance in the medium, an excess of one of them suppressing the oscillations. In its inducing effect on the rhythm K+ is partially replaced by Rb+, but not by Na+, Li+ or Cs+. While the glucose K+ balance is favourable for the manifestation of the rhythm, the addition of increasing levels of Na+, Li+ or Cs+ do not modify the period length. Nevertheless, at 0.3 M of Na+ or Li+ and 0.03 M of Cs+ rhythm disappears. The amplitude of oscillations depends on the level of the micro-elements furnished, especially on Mn2+. EDTA (1 × 10?3M) inhibits the rhythm.  相似文献   

17.
Rubidium uptake in potassium-starved cells followed biphasic kinetics in the micromolar and millimolar range and was independent of the temperature. In contrast, Rb+ uptake in normal-K+ cells followed a monophasic kinetics in the millimolar range and increased at temperatures higher than 30°C. Differences in the K m values and in the Arrhenius plots of Rb+ uptake suggest different uptake systems in K+-starved and in normal-K+ cells. In addition, the substantial inhibition of Rb+ uptake caused by carbonyl cyanide-m-chlorophenyl hydrazone indicates that these systems are strongly dependent on membrane voltage. Lithium (sodium) tolerance, influx, and efflux were separately studied. F. oxysporum was shown to be very tolerant to sodium, while lithium caused a specific toxic effect. Li+ uptake in K+-starved cells exhibits a monophasic kinetics with low affinity. Li+ efflux was not affected by external pH or addition of potassium to the medium, suggesting that a Na+/cation antiporter is not involved in this process. Received: 14 March 2000 / Accepted: 5 June 2000  相似文献   

18.
This study investigated the effects of dietary Bifidobacterium bifidum (BFD) and mannan-oligosaccharide (MOS), as a synbiotic, on the production performance, gut microbiology, serum biochemistry, antioxidant profile and health indices of broiler chicken. Six dietary treatments were T1 (negative control), T2 (positive control-20 mg antibiotic BMD kg−1 diet; BMD: bacitracin methylene disalicylate), T3 (0·1% MOS + 106 CFU BFD per g feed), T4 (0·1% MOS + 107 CFU BFD per g feed), T5 (0·2% MOS + 106 CFU BFD per g feed) and T6 (0·2% MOS + 107 CFU BFD per g feed). Significantly (P < 0·01) better growth performance and efficiency was observed in birds supplemented with 0·2% MOS along with 106 CFU BFD per g of feed compared to BMD and control birds. Supplementation with 0·2% MOS along with either 106 or 107 CFU BFD per g feed reduced (P < 0·01) the gut coliform, Escherichia coli, total plate count, and Clostridium perfringens count and increased the Lactobacillus and Bifidobacterium count. Significantly (P < 0·01) higher serum and liver antioxidant enzyme pool, serum HDL cholesterol and lower serum glucose, triglyceride, total cholesterol, cardiac risk ratio, atherogenic coefficient and atherogenic index of plasma were observed in birds supplemented with 0·2% MOS along with 106 CFU BFD per g of feed compared to control or BMD supplemented birds. Better production performance, gut microbial composition, serum biochemistry, antioxidant profile and health indices were depicted by broiler chicken supplemented with 0·2% MOS and 106 CFU BFD per g of feed.  相似文献   

19.
Despite recent advances, current polymeric organic cathode materials have failed to incorporate a high degree of lithium storage in a small molecular framework, resulting in low capacities relative to monomers. This report discloses the development of a lithium salt polymer of dihydroxyanthraquinone (LiDHAQS) capable of storing four Li+ per monomer. The combination of storing four Li+ per monomer and a low molecular weight monomer results in a capacity of 330 mA h g?1, a record for this class of material. The additional redox events responsible for added Li+ storage occur between 3.0 and 3.6 V versus Li/Li+ resulting in an average discharge potential of 2.5 V versus Li/Li+. These metrics combined yield a high energy density of 825 W h kg?1 which is a 55% improvement over commercial lithium cobalt oxide. The high performance of LiDHAQS makes it a promising material for next generation Li+ cathodes.  相似文献   

20.
Summary A transport system for branched-chain amino acids (designated as LIV-II system) inPseudomonas aeruginosa requires Na+ for its operation. Coupling cation for this system was identified by measuring cation movement during substrate entry using cation-selective electrodes. Uptakes of Na+ and Li were induced by the imposition of an inwardly-directed concentration gradient of leucine, isoleucine, or valine. No uptake of H was found, however, under the same conditions. In addition, effects of Na+ and Li+ on the kinetic property of the system were examined. At chloride salt concentration of 2.5mm, values of apparentK m andV max for leucine uptake were larger in the presence of Na+ than Li+. These results indicate that the LIV-II transport system is a Na+(Li+)/substrate cotransport system, although effects of Na+ and Li+ on kinetics of the system are different.  相似文献   

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