Uptake Of 54Mn Research Articles

Preferential uptake of zinc, manganese, and rubidium in rat brain tumor

The search for radionuclides that can be an index of viability in proliferating cells is important for nuclear medicine diagnosis of brain tumors. On the basis of the finding that 65Zn is preferentially taken up in rat brain tumors, the uptake of various radionuclides was examined in rat brain tumor by using the multitracer technique. Male Fisher rats were intrahippocampally injected with C6 glioma cells. Fourteen days after implantation, the radioactive multitracer solution was injected into the tail vein of tumor-bearing rats. One hour after intravenous injection, the uptake of 65Zn, 83Rb and 54Mn was relatively high in C6 glioma of 15 radionuclides detected, and was much higher than in other brain regions and in the blood. It is likely that rubidium and manganese, in addition to zinc, are preferentially taken up by tumors in the brain.

Incorporating soil structure and root distribution into plant uptake models for radionuclides: toward a more physically based transfer model

Most biosphere and contamination assessment models are based on uniform soil conditions, since single coefficients are used to describe the transfer of contaminants to the plant. Indeed, physical and chemical characteristics and root distribution are highly variable in the soil profile. These parameters have to be considered in the formulation of a more realistic soil–plant transfer model for naturally structured soils. The impact of monolith soil structure (repacked and structured) on Zn and Mn uptake by wheat was studied in a controlled tracer application (dye and radioactive) experiment. We used Brilliant Blue and Sulforhodamine B to dye flow lines and 65Zn and 54Mn to trace soil distribution and plant uptake of surface-applied particle-reactive contaminants. Spatial variation of the soil water content during irrigation and plant growth informs indirectly about tracer and root location in the soil profile. In the structured monolith, a till pan at a depth of 30 cm limited vertical water flow and root penetration into deeper soil layers and restricted tracers to the upper third of the monolith. In the repacked monolith, roots were observed at all depths and fingering flow allowed for the fast appearance of all tracers in the outflow. These differences between the two monoliths are reflected by significantly higher 54Mn and 65Zn uptake in wheat grown on the structured monolith. The higher uptake of Mn can be modelled on the basis of radionuclide and root distribution as a function of depth and using a combination of preferential flow and rooting. The considerably higher uptake of Zn requires transfer factors which account for variable biochemical uptake as a function of location.

Mucosal uptake and whole-body retention of dietary manganese are not altered in beta2-microglobulin knockout mice.

To further examine the interrelationships between manganese and iron absorption, the mucosal uptake, initial rate of loss, whole-body retention, and tissue distribution of an orally administered 54Mn radiotracer were compared between normal and beta2-microglobulin knockout [beta2m(-/-)] mice. These mutant mice are commonly used as a model for the study of human hemochromatosis, a hereditary iron-overload disease. Initial uptake of 54Mn by the intestinal mucosa, the liver, and the brain was not different between the two strains. The mutant mice had much higher concentrations of nonheme and total iron in the liver, but hepatic manganese, copper, magnesium, and zinc concentrations were similar between the two strains. In summary, the mucosal uptake and whole-body retention of manganese and tissue manganese concentrations were not altered in beta2m(-/-) mice; this suggests that normal homeostasis of manganese is not affected by the altered HFE protein-beta2m complex in these mice.

Dietary uptake, retention and tissue distribution of 54Mn, 60Co and 137Cs in the rainbow trout ( Oncorhynchus mikiss Walbaum)

The theoretical values of the steady-state trophic transfer factor, expressed on a wet weight basis in trout, are 0.0766 for 54Mn, 0.0777 for 60Co and 1.45 for 137Cs. The two corresponding half-lives of the depuration kinetics for these elements are 8 and 1120 days, 4 and 170 days and 11 and 940 days, respectively. At the end of the uptake phase, the highest concentrations of 54Mn were found in the liver, 60Co in the kidneys and 137Cs in the digestive tract. After 73 days of depuration, the highest concentrations of 54Mn were detected in the fins, 60Co in the kidneys and 137Cs in the muscles. In general, 54Mn was concentrated in the bony and cartilaginous tissues, 60Co in skin, head, bone and muscle and 137Cs in muscle.

Identification of the Escherichia coli K-12 Nramp orthologue (MntH) as a selective divalent metal ion transporter.

The Escherichia coli mntH (formerly yfeP) gene encodes a putative membrane protein (MntH) highly similar to members of the eukaryotic Nramp family of divalent metal ion transporters. To determine the function of E. coli MntH, a null mutant was created and MntH was overexpressed both in wild-type E. coli and in the metal-dependent mutant hflB1(Ts). At the restrictive temperature 42 degrees C, the mntH null mutation reduces the suppression of hflB1(Ts) thermosensitivity by exogenous divalent metals. Conversely, overexpression of MntH restores growth at 42 degrees C, increases suppression of the ts phenotype by Fe(II) and Ni(II) and renders hflB1(Ts) cells hypersensitive to Mn(II). Transport studies in intact cells show that MntH selectively facilitates uptake of 54Mn(II) and 55Fe(II) in a temperature-, time- and proton-dependent manner. Competition studies in uptake assays and growth inhibition experiments in hflB1(Ts) mutants together indicate that MntH is a divalent metal cation transporter of broad substrate specificity. The functional characteristics of MntH suggest that it corresponds to the previously described manganese transporter of E. coli. This study indicates that proton-dependent divalent metal ion uptake has been preserved in the Nramp family from bacteria to humans.

Manipulating iron availability in nearshore waters

The consideration of iron effects on marine ecosystems has focused mainly on high‐nitrate low‐chlorophyll regions, but iron likely has an equally important regulatory role in coastal waters. Iron requirements of neritic phytoplankton not only are comparatively high but also differ substantially among species, so that iron fluctuations within metal‐replete systems should strongly influence the composition and distribution of phytoplankton assemblages. But unlike the simplicity of testing iron effects in iron‐depleted waters, ascertaining iron effects in apparently replete waters has been forestalled by a lack of experimental tools that can regulate iron availability independent of other bioactive metals in seawater. I present here the results of size‐fractionated shipboard culture experiments using the fungal siderophore desferriferrioxime B (DFB) to regulate iron availability in coastal upwelling waters. Addition of excess DFB essentially eliminated 59Fe uptake by both phytoplankton and heterotrophic bacteria over a 6‐h period and allowed only marginal iron uptake over 5 d of incubation. Carbon uptake by small (0.2–5.0‐ µm) phytoplankton was immediately curtailed upon addition of DFB, signifying a rapid onset of iron stress. In contrast, short‐term (0–6 h) carbon uptake by larger (&5.0‐ µm) phytoplankton was not affected, indicating that larger cells contained significant iron reserves. Nonetheless, carbon assimilation was substantially lower in DFB treatments relative to the controls after 5 d of incubation. Uptake of 54Mn, 65Zn, and 57Co was not immediately affected by DFB but then slowed after 4 h and was significantly lower after 5 d, presumably because iron limitation lowered the cellular requirements for these bioactive metals. These findings demonstrate that DFB can be used to manipulate biologically accessible iron to determine how iron affects algal community structure and carbon cycling in iron‐replete waters.

The Yfe system of Yersinia pestis transports iron and manganese and is required for full virulence of plague.

Iron acquisition in Yersinia pestis is fundamental to the success of plague pathogenesis. We have previously identified an approximately 5.6 kb region (yfe) of Y. pestis genomic DNA, capable of restoring iron-deficient growth but not siderophore production to an Escherichia coli mutant (SAB11) incapable of synthesizing the siderophore, enterobactin. The yfe locus of Y. pestis, found in both pigmented (Pgm+) and nonpigmented (Pgm-) strains, comprises five genes arranged in two distinct operons (yfeA-D and yfeE ). The larger of these, yfeABCD, encodes an ABC transport system, whose expression is iron and Fur regulated and is repressed in cells grown in the presence of manganese. Cells from a Pgm-, Yfe- (DeltayfeAB ) mutant strain of Y. pestis exhibited reduced transport of both 55Fe and 54Mn. Furthermore, cells containing an intact yfe locus showed reduced 55Fe uptake when competing amounts of MnCl2 or ZnCl2 were present, whereas 54Mn uptake was inhibited by FeCl3 but not by ZnCl2. Similarly, yfe mutants of Y. pestis exhibited growth defects on media supplemented with the iron chelators 2,2'-dipyridyl or conalbumin. These growth defects were not relieved by supplementation with MnCl2. A ybt-, DeltayfeAB mutant of Y. pestis was completely avirulent in mice infected intravenously (LD50 > 1.7 x 107 cfu) compared with its parental ybt-, yfe+ strain, which had an LD50 of < 12. In addition, compared with its ybt+, yfe+ parent, a ybt+, DeltayfeAB mutant of Y. pestis had an approximately 100-fold increase in the LD50 from a subcutaneous route of infection. These data suggest that the Yfe and Ybt systems may function effectively to accumulate iron during different stages of the infectious process of bubonic plague.

Geomicrobial transformation of manganese in Gorda Ridge event plumes

Event plumes form as episodic discharges of large volumes of hydrothermal solutions in response to magmatic diking/eruptive events. In consequence, event plumes represent the sudden injection of exploitable reduced chemical substrates, as well as inhibitory constituents, and likely induce successional changes in the microbial community structure and activity within event plume waters. In response to a major seismic event detected beginning 28 February 1996 at the northern Gorda Ridge, a series of three rapid response and follow-up cruises (GREAT 1, 2 and 3) were mounted over a period of three months. This report focuses on time-series measurements of manganese geomicrobial parameters in the two event plumes found in association with this seismic event. Scanning transmission electron microscopy, elemental microanalysis, and radioisotope ( 54Mn) uptake experiments were employed on samples collected from vertical and tow-yo casts from the three cruises. Numbers of bacteria and ratios of metal precipitating capsuled bacteria to total bacteria were greatest in the youngest (days old) plume, EP96A, found during GREAT 1; however, when normalized to the hydrothermal temperature anomaly, the greatest values were found in a second event plume, EP96B, discovered during GREAT 2 (up to 1 month old). Early capsule bacteria and particulate Mn distributions may have been influenced by entrainment of resuspended sediment, while those of the oldest (2–3 months) plume sample may have been subjected to preferential aggregation and particle settling.

Evidence for non-transferrin-mediated uptake and release of iron and manganese in glial cell cultures from hypotransferrinemic mice.

Transferrin (Tf) is accepted as the iron mobilization protein, but its role in transport of other metals is controversial. In this study, we used mixed glial cultures from hypotransferrinemic (Hp) mice to determine the dependence of these cells on transferrin for iron and manganese delivery and release. Hp mice have a splicing defect in the transferrin (Tf) gene, resulting in < 1% of the normal plasma levels of Tf. Cellular iron and manganese uptake increases over 24 hr in cultures of normal and Hp glial cells in the presence of standard concentrations of Tf in the media; although total 59iron uptake in the Hp mouse cultures was 2X greater than normal, 54Mn uptake was similar between the two groups. The absence of Tf in the media resulted in a significant increase in 59iron uptake in both normal and Hp glial but did not affect Mn uptake. Elevated Tf (10X normal) in the media reduced both 59iron and 54Mn uptake. Efflux of 59Iron and 54Mn occurred in normal and Hp cultures, indicating the existence of a dynamic exchange of metals, and that intracellular Tf is not necessary for metal release. However, in the absence of Tf in the media, significantly more iron was retained in the cells than if Tf were present in both normal and Hp glial cultures. 54Mn release was minimally affected by extracellular Tf. The data demonstrate that Tf is not required for iron and Mn uptake into glial cells. These data further demonstrate a dynamic metal exchange system for glial cells which is not dependent on intracellular Tf.

Effect of application time of radionuclides on their root uptake by Chinese cabbage and radish

For investigating the effect of radionuclide deposition time on root uptake of 54Mn, 60Co, 85Sr and 137Cs by Chinese cabbage and radish, a mixed solution of the radionuclides was applied to the soil surfaces in culture boxes placed in a greenhouse at 4 different times during plant growth. Soil-to-plant transfer factor (TF) was determined on the basis of radioactivity in unit area of soil. In Chinese cabbage and, roughly speaking, in radish, TF of 85Sr decreased with increasing time between sowing and the radioactivity application. TFs of the other radionuclides were the highest at the third or last application. Concentrations of the radionuclides in soil were examined after harvests. They decreased exponentially with increasing soil depth and most radioactivity remained near the surface. TFs of the radionuclides applied 2 d before sowing were higher than those aged for 1 year by factors of 3–10 depending on radionuclide and plant species.

Effects of iron deficiency and iron overload on manganese uptake and deposition in the brain and other organs of the rat.

Manganese (Mn) is an essential trace element at low concentrations, but at higher concentrations is neurotoxic. It has several chemical and biochemical properties similar to iron (Fe), and there is evidence of metabolic interaction between the two metals, particularly at the level of absorption from the intestine. The aim of this investigation was to determine whether Mn and Fe interact during the processes involved in uptake from the plasma by the brain and other organs of the rat. Dams were fed control (70 mg Fe/kg), Fe-deficient (5-10 mg Fe/kg), or Fe-loaded (20 g carbonyl Fe/kg) diets, with or without Mn-loaded drinking water (2 g Mn/L), from day 18-19 of pregnancy, and, after weaning the young rats, were continued on the same dietary regimens. Measurements of brain, liver, and kidney Mn and nonheme Fe levels, and the uptake of 54Mn and 59Fe from the plasma by these organs and the femurs, were made when the rats were aged 15 and 63 d. Organ nonheme Fe levels were much higher than Mn levels, and in the liver and kidney increased much more with Fe loading than did Mn levels with Mn loading. However, in the brain the increases were greater for Mn. Both Fe depletion and loading led to increased brain Mn concentrations in the 15-d/rats, while Fe loading also had this effect at 63 d. Mn loading did not have significant effects on the nonheme Fe concentrations. 54Mn, injected as MnCl2 mixed with serum, was cleared more rapidly from the circulation than was 59Fe, injected in the form of diferric transferrin. In the 15-d-rats, the uptake of 54Mn by brain, liver, kidneys, and femurs was increased by Fe loading, but this was not seen in the 63-d rats. Mn supplementation led to increased 59Fe uptake by the brain, liver, and kidneys of the rats fed the control and Fe-deficient diets, but not in the Fe-loaded rats. It is concluded that Mn and Fe interact during transfer from the plasma to the brain and other organs and that this interaction is synergistic rather than competitive in nature. Hence, excessive intake of Fe plus Mn may accentuate the risk of tissue damage caused by one metal alone, particularly in the brain.

Aluminum alters iron and manganese uptake and regulation of surface transferrin receptors in primary rat oligodendrocyte cultures

Transferrin (TO is a major transport protein for both iron (Fe) and aluminum (AI), as well as manganese (Mn) and it can mediate cellular uptake of these elements via cell surface Tf receptors. To study the effect of Al-Tf on Tf receptor regulation, primary oligodendrocyte cultures were prepared from cortices of newborn rats. The effects of Al-Tf on 54Mn and 59Fe uptake were compared to those of apo-, Fe-, or Mn-Tf (1.25 μM). To examine changes in cell surface Tf binding capacity, preincubation (4 h, 37°C) was performed with apo-, AI- or Fe-Tf and homologous receptor binding studies were subsequently conducted with 125I-Fe-Tf at 4°C. Incubation with Al-Tf, but not with equimolar amounts of Al chloride or Al citrate, led to dose-related increases in cellular Al. Incubation with either Al- or Fe-Tf decreased 59Fe uptake, while incubation with either Al- or Mn-Tf decreased 54Mn uptake. Surface Tf receptor sites/cell were 1.05, 0.60 and 0.46 x 10 5 after incubations with equivalent amounts of apo-, Fe-, and Al-Tf respectively. The data suggest that Al-Tf down-regulates surface Tf receptors on oligodendrocytes and can limit Fe and Mn uptake through this mechanism.

Uptake and translocation of 54Mn and 65Zn applied on foliage and bark surfaces of balsam fir [ Abies balsamea (L.) Mill.] seedlings

Uptake and translocation of 54Mn and 65Zn in balsam fir [ Abies balsamea (L.) Mill.] seedlings were studied with the radioisotopes applied directly on shoot or main-stem surfaces in a growth chamber. Concentration and distribution of the absorbed radioisotopes in different plant parts depended on distances between source (the application site) and sink (the rest of the seedling), as well as on tissue growth activity. Acidic wetness significantly enhanced radioisotope absorption. 54Mn and 65Zn were found to be concentrated primarily in 1-year old needles at the middle and top levels of the seedling crown. There were significant ( P < 0.05) differences in accumulation (Bq g −1) between 54Mn and 65Zn in needles and twigs from foliar uptake. The absorption by seedlings (including the washed application shoot) 70 days after application was 24–32% of the remaining activities for 54Mn and 25–30% for 65Zn. Less than 1% of the absorbed isotopes was translocated from the bark application sites to other plant organs, whereas more than 54% of the activity absorbed at 1-year old shoots moved to the rest of the seedling.

Axonal transport of manganese and its relevance to selective neurotoxicity in the rat basal ganglia

The present study provides evidence for anterograde axonal transport of manganese (Mn) in the basal ganglia. Microinjections of 54Mn into rat substantia nigra or striatum revealed region-specific accumulation and retention of the isotope in globus pallidus, striatum, thalamus and substantia nigra for up to at least 48 or 72 h respectively. Within 4 h after intrastriatal injection of 54Mn, radioactivity accumulated in the substantia nigra, suggesting axonal transport of the metal. Subsequent studies using bilateral 54Mn injections into striatum or substantia nigra and unilateral colchicine injections into or transection of the medial forebrain bundle confirmed axonal transport of Mn through these fibres. Selective destruction of the striatonigral or nigrostriatal pathways using quinolinic acid or 6-hydroxydopamine 2 weeks before injection of the isotope, revealed uptake of 54Mn by cell bodies of both γ-aminobutyric acidergic striatal and dopaminergic nigral neurons and subsequent anterograde transport through sriatonigral or nigrostriatal fibres. In addition, the quinolinic acid-lesioned striatum three times more radioactivity than the intact striatum. In conclusion, the present data suggest that both glial cells and striatonigral and nigrostriatal neurons are potential targets for Mn toxicity. These results and the selective neurotoxicity of Mn are discussed with respect to the iron transport protein transferrin, transferrin receptors, the iron storage protein ferritin, and mitochondrial dysfunction.

Effects of some chelating agents on the uptake and distribution of 54Mn(II) in the brown trout (Salmo trutta).

The effects of humic acids, which are natural metal-complexing compounds, and potassium ethylxanthate, sodium diethyldithiophosphate, sodium dimethyldithiocarbamate, and sodium diethyldithiocarbamate, which are sulphur-containing man-made chelating agents, on the uptake and tissue distribution of 54Mn(II) were studied in brown trout (Salmo trutta). Fish were exposed for 7 days to 0.1 microgram Mn(II).l-1 as MnCl2 (1 microCi 54MN.l-1) with or without chelating agents. Examination of the partition of Mn between octanol and a Tris-HCl buffer in the presence of these compounds was also performed. Humic acids had only small effects on Mn uptake and distribution in trout, probably because of the low stability of Mn-humate complexes. Partition of Mn in the presence of potassium ethylxanthate, sodium diethyldithiophosphate, sodium dimethyldithiocarbamate, and sodium diethyldithiocarbamate between octanol and Tris-HCl buffer showed formation of lipophilic complex with the latter two compounds, but not with the former. However, these four chelating agents all decreased Mn uptake in the trout by 40-45%. These substances also changed the distribution of Mn within the fish, with a higher proportion of the metal being present in some visceral organs and a smaller proportion being localized in some non-parenchymateous tissues, such as skins, fins and bones. The mechanisms underlying these effects are not known. However, the interaction of chelating agents with the Mn, although weak, may have partially withdrawn the metal from the uptake process in the gills. The redistribution of Mn in the fish may be due to the binding of the metal to complexing compounds which have reached the intestinal lumen.(ABSTRACT TRUNCATED AT 250 WORDS)

Uptake and release of 54Mn and 60Co in Fucus vesiculosus L. and its epiphytes

Fucus vesiculosus L. with epiphytic Pilayella littoralis (L.) Kjelm. was collected at a locality where contamination by 54Mn and 60Co was relatively low and then transplanted to a locality in the vicinity of the Barsebäck nuclear power plant in the Öresund, southern Sweden. The reverse process was also carried out. The highest uptake of the two radionuclides discharged from the nuclear power plant was observed in the filamentous epiphytic P. littoralis. Differences in uptake of 60Co were also observed between tissues of different ages in F. vesiculosus, with slightly higher uptake in the new vegetative fronds. P. littoralis was succeeded as epiphyte by Enteromorpha intestinalis (L.) Link and Cladophora sp. and the highest uptake of both radionuclides was observed in Cladophora sp. Compared with the native Fucus plant at Barsebäck, the transplanted Fucus plants showed about the same activity concentrations of 54Mn while the 60Co concentrations in the transplanted plants were higher than in the native plants after about 4 months. The release of 54Mn and 60Co was most rapid in the epiphytic P. littoralis. Biological half-lives were found to be about 10 days for P. littoralis and about 40 days for new vegetative fronds of F. vesiculosus. Longer half-lives were found for 1-year-old tissues of F. vesiculosus: about 95 and 165 days for 54Mn and 60Co, respectively. One year after transplantation about 30% of the initial activity concentration of 60Co was still present in the older parts of the F. vesiculosus plants. The differences in uptake of 54Mn and 60Co illustrate the difficulty encountered in comparing results from different algal species.

A radiotracer study of cerium and manganese uptake onto suspended particles in Chesapeake Bay

The oxidation kinetics of Ce (III) and Mn(II) were studied in Chesapeake Bay in March and July 1990 to establish the role of water column redox processes in contributing to Ce anomalies observed in this estuary (Sholkovitz and Elderfield, 1988; Sholkovitz et al., 1992). Oxidation was measured by adding Mn(II) and Ce (III) to freshly collected water samples as radiotracers and measuring their uptake onto the ambient suspended particle assemblage. Mn(II) oxidation was measured by following the uptake of 54Mn(II) onto suspended particles and utilizing protocols established by other workers to distinguish oxidation from Mn(II) adsorption. The same protocols were applicable to Ce (III), using 139Ce(III)and were supported by the use of 152Eu(III) as a nonredox reactive control. Specific rates of Ce (III) and Mn(II) oxidation measured at a station in the North Bay (depth = 4 m) in July were 2016% per day and 4032% per day, respectively. In March at the same station, the specific rate of Mn(II) oxidation was only 10% per day and Ce (III) oxidation was undetectable. Both Ce (III) and Mn(II) oxidation processes were inhibited by azide, indicating that they were microbially mediated. The seasonal differences probably reflect strong seasonal variation in the abundance of Mn oxidizing bacteria. No Ce (III) oxidation occurred in samples collected below the oxic/anoxic interface in July. The specific rates of oxidation for both elements were over 1000 times higher than those measured in the Sargasso Sea. However, the specific rates for Ce (III) and Mn(II) were very similar to each other. This fact, coupled with similar spatial and temporal trends for specific oxidation rates, suggests a common mechanism of oxidation of both elements which may be significant in a wide range of marine environments.

Saturable transport of manganese(II) across blood-nerve barrier of rat peripheral nerve.

To determine whether the blood-nerve barrier of the rat peripheral nerve transports manganese(II) (Mn) by a saturable mechanism similar to that found at the blood-brain barrier, we measured the uptake of 54Mn from blood into desheathed sciatic nerve and into cerebral cortex of awake rats at different plasma concentrations of unlabeled Mn using an intravenous infusion technique. The unidirectional influx (Jin) of Mn into sciatic nerve was facilitated and saturable, when steady-state plasma Mn ranged from 4 to 4,312 ng/ml (0.073-78.4 microM), as was the unidirectional influx of Mn into the cerebral cortex. Michaelis-Menten constants (Km and Vmax) and the passive diffusion constant (Kd), determined by nonlinear least squares, were as follows: for the blood-nerve barrier (sciatic nerve) Km = 4.7 microM, Vmax = 0.56 x 10(-3) nmol.s-1.g wet wt-1, and Kd = 6.3 x 10(-6) ml.s-1.g wet wt-1; for the blood-brain barrier (cerebral cortex) Km = 1.0 microM, Vmax = 0.40 x 10(-3) nmol.s-1.g wet wt-1, and Kd = 0.3 x 10(-6) ml.s-1.g wet wt-1. The results demonstrate facilitated concentration-dependent mechanisms of transport of Mn at the blood-nerve and blood-brain barriers.

Saturable Transport of Manganese(II) Across the Rat Blood‐Brain Barrier

Unanesthetized adult male rats were infused intravenously with solutions containing 54Mn (II) and one of six concentrations of stable Mn(II). The infusion was timed to produce a near constant [Mn] in plasma for up to 20 min. Plasma was collected serially and on termination of the experiment, samples of CSF, eight brain regions, and choroid plexus (CP) were obtained. Influx of Mn (JMn) was calculated from uptake of 54Mn into tissues and CSF at two different times. Plasma [Mn] was varied 1,000-fold (0.076-78 nmol/ml). Over this plasma concentration range, JMn increased 123 times into CP, 18-120 times into brain, and 706 times into CSF. CP and brain JMn values fit saturation kinetics with Km (nmol/ml) equal to 15 for CP and 0.7-2.1 for brain, and Vmax (10(-2) nmol.g-1.s-1) of 27 for CP and 0.025-0.054 for brain. Brain JMn except at cerebral cortex had a nonsaturable component. CSF JMn varied linearly with plasma [Mn]. These findings suggest that Mn transport into brain and CP is saturable, but transport into CSF is nonsaturable.

Manganese(II) dynamics and distribution in glial cells cultured from chick cerebral cortex

The kinetics of manganese(II) ion uptake and efflux have been investigated using tracer 54Mn(II) with glial cells cultured from chick cerebral cortex in chemically defined medium. The initial velocity of Mn(II) uptake versus [Mn(II)] exhibit saturation, with an apparent S0.5 approximately 18(+/- 3) microM. Both the rate and extent of Mn(II) uptake are inhibited by Ca(II), either added externally or preloaded into the glial cells. Preloading of glia with Mn(II) also inhibits the rate of external 54Mn(II) uptake. Zn(II) inhibits but Cu(II) activates Mn(II) uptake. Efflux of Mn(II) from preloaded cells occurs as a biphasic process, with rapid release of 30-40% of total cell Mn(II), then much slower release of the remainder. Permeabilization of cells with dextran sulfate also rapidly released ca. 30% of total cell Mn(II). High external Mn(II) enhanced both the rate and extent of Mn(II) efflux. CCCP, an uncoupler of oxidative phosphorylation, inhibited both Mn(II) uptake and efflux significantly, but addition of cyanide, ouabain, insulin, hydrocortisone, K+, or Nd(III) had no effect on either process. Taken together, these data suggest a model in which Mn(II) is brought across the plasma membrane by facilitated diffusion, binds to cytosolic protein sites, and is partitioned into the mitochondria by an active transport mechanism. The fact that the Mn(II) flux rates observed with cultured glia are much faster than those reported for overall uptake and efflux of brain Mn(II) in vivo suggests that the blood-brain barrier may play a significant role in determining these latter rates in whole animals.