Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Isolated segments of rat cortical (cTAL) and medullary (mTAL) thick ascending limbs were microperfused and the transepithelial net fluxes (JX) were determined by measuring the composition of the collected fluid with an electron microprobe. When perfused with symmetrical solutions both segments showed similar JNa and JCl and lumen-positive transepithelial voltage (Vte = 7-8 mV). JMg, JCa and JK were not significantly different from zero. When perfused with asymmetrical solutions (lumen 50 mM, bath 150 mM NaCl), the mean Vte were 23 mV and 17 mV in the cTAL and mTAL respectively; this rise was accompanied by significant increases in JMg and JCa in the cTAL, but not in the mTAL, and a marked increase in JK in both segments. It is concluded that, in the rat, divalent cations can be reabsorbed in the cTAL, and K+ can be reabsorbed in the cTAL and mTAL. The transport is voltage-dependent. The mTAL can reabsorb neither Mg2+ nor Ca2+, whatever Vte.
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PMID:Ca2+, Mg2+ and K+ transport in the cortical and medullary thick ascending limb of the rat nephron: influence of transepithelial voltage. 825 43

The distribution of the calcium binding protein, calretinin (CR) has been investigated immunohistochemically in the cerebral cortex of albino rats by light- and electron microscopy. At the light microscopical level the pattern of CR-immunoreactivity (ir) appeared very similar in all regions of the rat cerebral cortex. CR-immunoreactive cells were found sparsely in layer I to layer VI, and frequently also in the white matter of the corpus callosum. All CR-ir neurons revealed morphological characteristics of local interneurons. The calretinin positive interneurons could be grouped according to their laminar occurrence, dendritic arborization and the soma size into 5 cell type classes. Quantitative measurements were performed only in the visual cortex. CR-ir neurons were more frequent in the superficial layers II and III. In all other layers, CR-ir cells are sparsely distributed with no preferential laminar localization. At the electron microscopical level, CR-ir axonal boutons formed frequently symmetrical axo-dendritic contacts. In all animals we observed CR-ir axons forming also synaptses of asymmetrical type. In summary calretinin labelled an interneuronal subpopulation of the rat cerebral cortex, which seemed not to overlap in its distribution and labelled structures to those, containing the related calcium binding proteins parvalbumin and calbindin D-28k.
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PMID:The calcium-binding protein calretinin is localized in a subset of interneurons in the rat cerebral cortex: a light and electron immunohistochemical study. 837 59

Amyloid beta protein (A beta P) is the 40- to 42-residue polypeptide implicated in the pathogenesis of Alzheimer disease. We have incorporated this peptide into phosphatidylserine liposomes and then fused the liposomes with a planar bilayer. When incorporated into bilayers the A beta P forms channels, which generate linear current-voltage relationships in symmetrical solutions. A permeability ratio, PK/PCl, of 11 for the open A beta P channel was estimated from the reversal potential of the channel current in asymmetrical KCl solutions. The permeability sequence for different cations, estimated from the reversal potential of the A beta P-channel current for each system of asymmetrical solutions, is Pcs > PLi > PCa > or = PK > PNa. A beta P-channel current (either CS+ or Ca2+ as charge carriers) is blocked reversibly by tromethamine (millimolar range) and irreversibly by Al3+ (micromolar range). The inhibition of the A beta P-channel current by these two substances depends on transmembrane potential, suggesting that the mechanism of blockade involves direct interaction between tromethamine (or Al3+) and sites within the A beta P channel. Hitherto, A beta P has been presumed to be neurotoxic. On the basis of the present data we suggest that the channel activity of the polypeptide may be responsible for some or all of its neurotoxic effects. We further propose that a useful strategy for drug discovery for treatment of Alzheimer disease may include screening compounds for their ability to block or otherwise modify A beta P channels.
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PMID:Alzheimer disease amyloid beta protein forms calcium channels in bilayer membranes: blockade by tromethamine and aluminum. 838 Jun 42

In adult guinea pigs, unilateral labyrinthine lesions were inflicted by chloroform injections into the middle ear. Immunoreactivity for S100 protein (S100) in the vestibular nuclei was studied during compensation of lesion-induced postural asymmetry symptoms, i.e., nystagmus, asymmetrical head position. 1 h after unilateral labyrinthectomy, increased levels of astroglial S100 immunoreactivity were found in the superior vestibular nucleus and in the medial/lateral vestibular nucleus border region on the side contralateral to the deafferentation. Bilaterally, the astrocytic S100 immunoreaction increased in the lateral vestibular nuclei around Deiters neurons. Maximal expression of S100 was noted 3 h after the lesion. Subsequently, it diminished. Our data reveal that transsynaptically altered neuronal activity induces an astrocytic reaction which provides increased levels of S100 to the local neuropil. Calcium and zinc binding S100 proteins may play a functional role for the neuroplasticity during vestibular compensation.
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PMID:Expression of S100 protein in the vestibular nuclei during compensation of unilateral labyrinthectomy symptoms. 854 26

A remarkable duality concerning the role of intracellular Ca2+ ions is observed. At one side Ca2+ is a universal secondary messenger, and at the other side a prolonged increase of the Ca2+ concentration will lead to pathological conditions. This is the reason that Ca2+ signals occur in complex spatio-temporal patterns such as waves and oscillations. This behaviour reflects the existence of a fundamental heterogeneity at the level of the molecular and functional parameters that regulate the Ca2+ fluctuations. The molecular basis of the complex Ca2+ signals is the regenerative character of the inositol trisphosphate receptor (InsP3R) responsible for the release of Ca2+ from intracellular stores. In this work, we describe the qualitative and quantitative analysis of the expression of the InsP3R isoforms in various cell types. It appeared that there exist at least 5 different isoforms and that the isoforms of type II, IV and the newly described receptor of type V form a sub-family. The type I receptors are ubiquitous, but most cell types express in addition one or more isoforms. In the second part of this work, we describe the functional heterogeneity that results from the interaction of the InsP3R with InsP3 as well as with allosteric factors. In this study we demonstrate that the InsP3R isoforms show remarkable differences with respect to their sensitivity for InsP3. An extremely important modulator of the InsP3R is the Ca2+ ion itself. Cytosolic Ca2+ has a stimulatory as well as an inhibitory role. The Ca2+ present in the lumen of the store is also an important regulator of the InsP3R. In the third part of this work we have made a correlation between the observed molecular and functional heterogeneity and the fundamental physiological properties of complex Ca2+ signals, like quantal release, Ca2+ oscillations and Ca2+ waves. Both the isoform diversity and the regulation of the InsP3R by cytosolic and luminal Ca2+ are necessary for the fine-tuning of the Ca2+ signals. The isoform diversity may also play a role in the origin of asymmetrical signals present in polarised cells and in the InsP3-dependent signals through the plasma membrane and through the perinuclear membrane.
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PMID:[Molecular and functional diversity of inositol triphosphate-induced Ca(2+) release]. 857 71

The metabotropic glutamate receptor mGluR5 is a G-protein coupled receptor that plays a key role in release of Ca2+ from internal stores via inositol triphosphate mobilization. Western and Northern blot analyses revealed a greatly enhanced expression of mGluR5 in rats during early stages of hypothalamic development compared with the adult. This enhanced developmental expression provides an explanation for the dramatic physiological response of developing neurons to metabotropic glutamate receptor activation and supports the argument that metabotropic glutamate receptors may play an important role in hypothalamic development. During development, expression of the mGluR5 gene was reduced, not only in the hypothalamus but also in other regions of the brain. A differential decrease in mGluR5 protein was found in different brain regions with Western blot analysis. The hypothalamus showed a sixfold decrease in mGluR5 with development, whereas the cortex showed only a threefold decrease. Immunocytochemistry with an affinity-purified antibody against a peptide deduced from the cloned mGluR5 gene revealed selective expression in some regions in the adult hypothalamus. In the adult and developing (postnatal day 10) brain, immunoreactive neurons were found in the suprachiasmatic nucleus, preoptic area, lateral hypothalamus, and mammillary region, areas where the related metabotropic glutamate receptor mGluR1 is also found. In contrast, the ventromedial nucleus, an area critically involved in the regulation of food intake and metabolic balances, showed strong mGluR5 immunoreactivity but no mGluR1 immunoreactivity. Little or no mGluR5 staining was found in the neurosecretory neurons of the paraventricular, supraoptic, and arcuate nuclei. Ultrastructurally, mGluR5 was associated with the cytoplasmic face of the plasmalemma on hypothalamic dendrites, dendritic spines, and neuronal perikarya in the adult. The strongest immunoreactivity was found in patches on the membrane, sometimes associated with the postsynaptic side of synapses and sometimes associated with nonsynaptic dendritic or perikaryal membrane. Intense immunostaining was found on some astrocyte processes surrounding synaptic complexes containing asymmetrical synapses. These astrocytes would be in an ideal position to receive excitatory signals from glutamatergic axons. Unlike the punctate appearance of immunolabeling on neuronal membranes, astrocytes showed continuous staining along the plasma membrane.
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PMID:Metabotropic glutamate receptor mGluR5 subcellular distribution and developmental expression in hypothalamus. 857 26

Mitochondria can synthesize phosphatidyl-ethanolamine (PE) through phosphatidylserine decarboxylase (PS decarboxylase) activity or can import this lipid from the endoplasmic reticulum. In this work, we studied the factors influencing the import of PE in brain mitochondria and its utilization for the assembly of mitochondrial membranes. Incubation of rat brain homogenate with [1-3H]ethanolamine resulted in the synthesis and distribution of 3H-PE to subcellular fractions. Twenty-one percent of labeled PE was recovered in purified mitochondria. The import of PE in mitochondria was studied in a reconstituted system made of microsomes (donor particles) and purified mitochondria (acceptor particles). Ca2+ and nonspecific lipid transfer protein purified from liver tissue (nsL-TP) enhanced the translocation process. 3H-PE synthesized in membrane associated to mitochondria (MAM) could also translocate to mitochondria in the reconstituted system. Exposure of mitochondria to trinitrobenzensulfonic acid (TNBS) resulted in the reaction of more than 60% of 3H-PE imported from endoplasmic reticulum and of about 25% of 14C-PE produced in mitochondria by decarboxylation of 14C-PS. Moreover, the removal of the outer mitochondrial membrane by digitonin treatment, resulted in the loss of 3H-PE, but not 14C-PE. These results indicate that labeled PE imported in mitochondria is mainly localized in the outer mitochondrial membrane, whereas PE produced by PS decarboxylase activity is confined to the inner mitochondrial membrane. Phospholipase C hydrolyzed 25-30% of both PE radioactivity and mass of the outer mitochondrial membrane indicating an asymmetrical distribution of this lipid across the membrane.
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PMID:Import of phosphatidylethanolamine for the assembly of rat brain mitochondrial membranes. 860 65

1. Potassium currents were measured in the extensor digitorum longus muscle of normal and mdx mice, which lack the protein dystrophin, using the cell-attached and inside-out patch clamp techniques, in the presence of asymmetrical K+ concentrations (3 mM in the pipette, 160 mM in the bath). 2. In cell-attached patches, the delayed rectifier was the most commonly found potassium channel, with a density of roughly 8 channels microns-2. Outward macroscopic currents were activated in macropatches depolarized to potentials positive to -60 mV. The probability of opening reached half-maximal values around -40 mV for control patches and -31 mV for patches from mdx mice. 3. Tail currents were linear in the range between -60 and +20 mV, reversing close to -100 mV. The single channel current at 0 mV, estimated from non-stationary analysis of variance, was used in conjunction with the slope of the linear part of the tail current to calculate the single channel conductance, yielding a value of 19 +/- 1 pS. 4. At 0 mV, the delayed rectifier inactivated with two time constants, of 70 +/- 20 ms and 600 +/- 200 ms. Prepulses of 500 ms duration to different potentials produced incomplete inactivation with inactivation reaching 50% of its maximum at -50 mV. 5. Single channel activity was recorded using small pipettes. Both single channel conductance and kinetic behaviour were in agreement with the macroscopic current data. 6. In excised patches, the delayed rectifier current ran down, unmasking other K+ channels. A Ca(2+)-dependent K+ channel of 186 pS (BK-like channel) was found frequently in patches bathed in solutions containing appropriate concentrations of calcium, especially at stronger depolarizations. A K+ channel of 63 pS was unmasked in control excised patches bathed in solutions devoid of ATP. This channel was not observed in patches excised from mdx fibers.
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PMID:A patch-clamp study of delayed rectifier currents in skeletal muscle of control and mdx mice. 873 98

We have used a fluorescently-labeled dihydropyridine (FL-DHP) to vitally stain living Fucus zygotes during the establishment of cell polarity. Localization of FL-DHP is primarily at the plasma membrane and FL-DHP binding is competitively blocked by an unlabeled dihydropyridine. Distribution of FL-DHP is initially symmetrical before fixation of the polar axis, but becomes asymmetrical in response to a unilateral light gradient. The distribution of FL-DHP receptors can be relocalized when the direction of the photopolarizing stimulus is changed. Treatment of cells with cytochalasin B prior to axis fixation reversibly prevents localization of FL-DHP receptors. Observation of FL-DHP labeling by time-lapse fluorescence microscopy indicates that the existing receptors are redistributed during polar axis formation. The asymmetric distribution of FL-DHP receptors coincides temporally and spatially with increased local intracellular calcium ion concentrations, as measured by calcium green dextran. Based on the site, timing, photo-reversibility, and actin dependence of the asymmetric localization of FL-DHP receptors, we conclude that FL-DHP is a vital probe for the later stage of polar axis formation in Fucus zygotes. Furthermore, we propose that FL-DHP receptors correspond to ion channels that are transported to the future site of polar growth to create the changes in local calcium concentration required for polarity establishment.
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PMID:Polar localization of a dihydropyridine receptor on living Fucus zygotes. 883 57

In human placental syncytiotrophoblast brush-border (BBM, facing the mother) and basal-plasma membranes (BPM, facing to fetus) we have recently demonstrated the presence of calcaemic hormone-specific receptors for parathyroid hormone and calcitonin, which could be implicated in calcium transport from the mother to the fetus. It is well recognized that signal transducing G proteins (guanosinc nucleotide-binding proteins) can associate with various transmembrane receptors and effector proteins, and regulate a variety of second-messenger systems and ion channels. In this present paper, we investigated the presence of a variety of alpha and beta subunits of G proteins in both syncytiotrophoblast, BBM and BPM by Western blot technique. For the first time, we were able to demonstrate the presence of G proteins in the bipolar syncytiotrophoblast membranes, which were evaluated by immunoblotting using affinity purified antiserum raised against the alpha subunits of Gi1, Gi1/i2, Gi3, G0, Gq, Gs, G7 and against the beta subunits. In BBM, we identified the alpha subunits of Gi1, Gi3, G0, Gq, Gs (42, 46 kDa), Gz and beta subunits. The same alpha subunits of G proteins were found in BPM, although alpha subunits of Gi1, Gq, Gs (46 kDa) were located predominantly in the BBM, and the alpha subunit of G0 was found preferentially in BPM. Moreover, in BBM and BPM, a purified antisera raised against the alpha subunits of Gi1 and Gs, detected a 105 kDa protein and a 67 kDa protein, respectively. Interestingly, the 67 kDa protein was preferentially located in BBM, and none of these proteins were detectable in membranes prepared from brain (control). The asymmetrical distribution of the alpha subunits of G proteins among the two different placental bipolar membranes might reflect the very specialized function of these syncytiotrophoblast membranes in ions and nutrients transport from the mother to the fetus.
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PMID:Asymmetrical distribution of G proteins in syncytiotrophoblastic brush-border and basal-plasma membranes of human term placenta. 889 76


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