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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recognition of metal cations by biological systems can be compared with the geochemical criteria for isomorphous replacement. Biological systems are more highly selective and much more rapid. Methods of maintaining an optimum concentration, including storage and transfer for the essential trace elements, copper and iron, used in some organisms are in part reproducible by coordination chemists while other features have not been reporduced in models. Poisoning can result from a foreign metal taking part in a reaction irreversibly so that the recognition site or molecule is not released. For major nutrients, sodium, potassium, magnesium and calcium, there are similarities to the trace metals in selective uptake but differences qualitatively and quantitatively in biological activity. Compounds selective for potassium replace all the solvation sphere with a symmetrical arrangement of oxygen atoms; those selective for sodium give an asymmetrical environment with retention of a solvent molecule. Experiments with naturally occurring antibiotics and synthetic model compounds have shown that flexibility is an important feature of selectivity and that for transfer or carrier properties there is an optimum (as opposed to a maximum) metal-ligand stability constant. Thallium is taken up instead of potassium and will activate some enzymes; it is suggested that the poisonous characteristics arise because the thallium ion may bind more strongly than potassium to part of a site and then fail to bind additional atoms as required for the biological activity. Criteria for the design of selective complexing agents are given with indications of those which might transfer more than one metal at once.
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PMID:Recognition of metal cations by biological systems. 0 15

Calcium ions can trigger an emission of light from Veretillum cynomorium lumisomes (bioluminescent vesicles) under conditions where they are not lysed. This process does not require a metabolically-linked source of energy, but is dependent upon the nature of the ions present inside and outside the vesicles. The Ca2+-triggered bioluminescence is stimulated by an asymmetrical distribution of cations or anions. Either high internal sodium or high external chloride is required for the maximal effect. When sodium is present outside the structure and potassium inside, the slow inward diffusion of calcium is decreased. Unbalanced diffusion of internal cations also stimulates the bioluminescence, suggesting control of the calcium influx by an electrochemical gradient. It is assumed that rapid outward diffusion of sodium or inward diffusion of chloride generates an electrical potential difference (inside negative) which drives the Ca2+-influx. With purified lumisomes it has been shown that Ca2+-triggered bioluminescence and calcium uptake (presumably net uptake) were correlated. In two instances uptake of the lipophilic cation dibenzyldimethylammonium has given direct evidence for the existence of a potential difference. With NaCl-loaded vesicles, it has not been possible to demonstrate an uptake of lipophilic cations but experiments with 22Na and 42D indicated a higher rate of sodium efflux, in accord with the proposed hypothesis.
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PMID:Control of the Ca2+-triggered bioluminescence of Veretillum cynomorium lumisomes. 3 Apr 80

Temperature-induced conformational changes in the anticodon region of yeast tRNATyr were studied by EPR spectroscopy. The spin label 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl was attached to the N6-(delta2-isopentenyl)-adenosine residue in tRNATyr, previously made reactive by iodination. The labelled tRNATyr gave an asymmetrical triplet spectrum typical of rapidly tumbling nitroxide, with a rotational correlation time (tauc) of 0.65 ns. Spin-labelled tRNATyr was exposed to heating and cooling in three different buffers each with or without MgCl2. In each case the Arrhenius plot of --log tauc vs. inverse absolute temperature gave two straight lines, intersecting at a critical temperature (tcr). Above tcr, the anisotropy of the spectrum was not reduced and the activation energy of motion increased, indicating that the transition is associated with a conformational change of the macromolecule. Transitions in 0.05 M potassium phosphate (pH 8.0) and 0.02 M Tris - HC1 (pH 7.0) were observed at potassium phosphate (pH 8.0) and 0.02 M Tris - Hc1 (pH 7.0) were observed at approx. 37 degrees C. When 0.01 M mgCl2 was present in these buffers, transitions were shifted to 46 degrees and 53 degrees C, respectively. Transitions in 0.01 M sodium cacodylate were observed at temperatures which are significantly lower. Since all these transitions occur at temperatures considerably below those required to melt the helical regions of tRNA, and at least approximately 10 degrees C below those reported to break tertiary interactions, it is supposed that they reflect some reorientation of the anticodon region, e.g. a change in tilt of the bases.
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PMID:Conformational changes in yeast tRNATyr revealed by EPR spectra of spin-labelled N6-(delta2-isopentenyl)-adenosine residue. 20 Feb 69

1. Kinetics of inactivation of sodium channels in myelinated nerve from Rana pipiens were studied at 4.5 degrees C using the voltage clamp technique of Dodge & Frankenhaeuser (1958).2. Potassium currents were blocked by cutting the internodes in 20 mM-TEA-Cl + 100 mM-KCl and by adding 12 mM-TEA-Cl to the external Ringer. Leakage and capacitative currents were subtracted electronically.3. Kinetics of recovery from inactivation of the sodium channels were studied by inactivating the channels with a large depolarizing prepulse and allowing the channels to recover at different potentials; the extent of recovery was measured by applying a test pulse at various times after the prepulse.4. Kinetics of development of inactivation were studied by two different methods. The first was to measure the decay of sodium current under a maintained depolarization. The second method was to measure the decay of the peak sodium current in a test pulse as a function of time after the onset of a maintained depolarization. These two methods yielded similar results for the kinetics of inactivation development.5. Contrary to expectations of the Hodgkin-Huxley formalism, the time course of recovery from and development of inactivation is not strictly exponential. Rather, recovery from complete inactivation shows an initial delay which depends on recovery potentials. Development of inactivation at a fixed potential exhibits at least two exponentials.6. The steady-state inactivation curve h(infinity)(E) is asymmetrical and is fitted better by 1/[1+exp (A(1)E+B(1)) +exp (A(2)E+B(2))] than by 1/[1+exp (AE+B)].7. Most of the above kinetic observation on inactivation can be fitted by the following modification of the h system of the Hodgkin-Huxley formalism: [Formula: see text]8. In the analysis it was not necessary to modify the concept of two separate processes, activation and inactivation, governing the opening and closing of the sodium channels.
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PMID:Inactivation of sodium channels: second order kinetics in myelinated nerve. 30 88

It is classically considered that cochlear fatigue and acoustic trauma occur when intensity is such that the ear is saturated, i.e. when the microphonic potential fails to increase in a linear fashion in relation to intensity and when distorsion appears. The present report concerns a study in the guinea pig of the relationship between the non-linearity of microphonic responses, and their fatigability. The results show that fatigability is related not only to non-linearity but also to the asymmetry of responses. The asymmetry of microphonic responses may be interpreted as reflecting an asymmetrical ionic flow at the upper pole of hair cells, resulting in an accumulation of potassium ions within and around hair cells and thereby creating a depression of responses.
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PMID:[Relationship between cochlear fatigue and the asymmetrical non-linearity of microphonic responses in the guinea pig (author's transl)]. 53 88

A new method for the determination of lipid membrane surface tension was developed. Advantages of this method are that it allows for multiple measurements on a single membrane, is fast and direct not requiring empirical corrections, may be applied for dynamical surface-tension measurements and may be used with thin films and asymmetrical electrolytes. The pressure and radius of a bubble are measured. A piezoresistive sensor is used to minimize the transducer compliance. By moulding the sensor to a brass plate a resolution of 0.025 mm H2O (0.25 Pa) is obtained. The bubble is filmed using a videocamera and the radius of the bubble determined with the aid of a microcomputer. Data for monoolein/hexadecane in potassium chloride solutions and a cooling curve are presented and compared with previous results.
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PMID:Monitoring the surface tension of lipid membranes by a bubble method. 159 83

A chamber filled with salt solution and separated into two compartments by a Teflon partition with a pore of 700 microns diameter was used to investigate the action of aureofuscin, a polyene antibiotics, on a planar lipid bilayer. The pore was covered with a bilayer formed by a N-decane solution of lecithin and cholesterol (20 mg/ml and 5 mg/ml). The electrical property and ionic permeability of the bilayer were studied by using voltage clamp method. Decrease of the bilayer resistance and the channel-like activity could be observed 20 min after the addition of aureofuscin (10-20 micrograms/ml) to one compartment. The existence of a transmembrane voltage and ionic gradient were not necessary for the channel-forming activity of aureofuscin. Discrete current steps were recorded at a concentration of 1.4 micrograms/ml aureofuscin, with a predominant unit conductance of 4-6 pS in a symmetric KCl, solution of 100 mmol/L. By using Goldmann-Hodgkin-Katz voltage equation the ionic selectivity of the channel formed by aureofuscin was estimated by the reversal potential measured in the asymmetrical solution system. The results showed that aureofuscin channels were more permeable to potassium ion than to chloride ion (PK/PCl approximately 5.2). These data may be used to explain the action of aureofuscin on neurotransmitter release and muscle membrane potential in addition to providing some explanation on its curing effect in clinical use.
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PMID:[Ionic channels formed in the lipid bilayer membranes by aureofuscin, a polyene antibiotics]. 171 13

The surface tension of glycerylmonooleate-hexadecane lipid bilayer membranes and the lifetime of gramicidin A channels were measured at various concentrations of the surrounding solutions. For HCl the surface tension is essentially constant at approximately 5 mN/m up to approximately 1 M, whereas the average lifetime increases approximately 40-fold. At higher concentrations the surface tension decreases markedly. For CsCl the surface tension is constant up to about 1 M then increases with salt level. The average lifetime in this case increases about sixfold. In both cases the lifetime levels off and even decreases at higher salt levels. The increase in lifetime observed with ion activity is therefore qualitatively different from, and not explained by, the established dependence of lifetime on membrane properties (Elliot, J.R., D. Needham, J.P. Dilger, and D.A. Haydon. 1983. Biochim. Biophys. Acta. 735:95-103). We have previously proposed that ion occupancy is a determinant of channel stability, and to test this hypothesis the voltage dependence of channel lifetime was measured in asymmetrical solutions. For the case of a potassium chloride solution on one side of the membrane and a hydrogen chloride solution, on the other, the voltage dependence of the lifetime is asymmetrical. The asymmetry is such that when the electrical field is applied in the direction of the chemical gradient for each of the ions, the channel lifetime approaches, at increasing field strengths, that of a symmetrical solution of the respective ion. The voltage dependence of the surface tension, on the other hand, is negligible for the range of voltages used. These results, and the earlier findings that the order of the lifetimes for the alkali cations generally agree with the order of the permeability selectivity of the gramicidin A channel, support the hypothesis that ion occupancy is a major factor determining the lifetime of gramicidin A channels. The effects of multivalent blockers and osmotic agents were also tested. Ba2", La3+,and Mg2" decrease the lifetime and conductance markedly. Sucrose and urea increase the lifetime and decrease the conductance. The voltage dependence of the lifetime in symmetrical solutions was examined. Contrary to previous reports it was found that the lifetimes for K+, Cs', and H+ are voltage dependent. For 0.5 M HCI the lifetime decreases monotonically by .60% at 150 mV, and for 0.5 M KCI the lifetime increases by -60% at 200 mV. Below 10 mM there is no effect of voltage for H+, K+, and Cs+. These effects of blockers, osmotic agents, and voltage on the lifetime, as well as the lack of effect of voltage at low salt levels, are consistent with the occupancy hypothesis.
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PMID:Evaluation of surface tension and ion occupancy effects on gramicidin A channel lifetime. 245 76

A study has been made with human red cells of sodium movements that are sensitive to the drug furosemide. The aim was to see if furosemide-sensitive movements that are symmetrical (exchange) became asymmetrical (net transport) on replacement of chloride with nitrate as the major external anion. Cells were incubated for 4 h at 37 degrees C with 140 mM sodium, and chloride or nitrate as the principal anion. Under a variety of conditions (presence and absence of ouabain or furosemide, or both) the cell sodium concentration was always higher when chloride was replaced with nitrate. The cells became leakier to sodium. Tracer studies indicated that, in contrast to the results in chloride medium, the decrease in sodium influx was greater than the fall in efflux when furosemide was added to cells in nitrate medium. The results confirm that the sensitivity of sodium efflux to furosemide depended on chloride. However, influx showed a different sensitivity in that furosemide still inhibited in cells incubated in nitrate medium. The stimulation of sodium influx with nitrate medium was independent of external potassium (10-50 mM) and the furosemide-sensitive influx was also constant. It is concluded that symmetrical transmembrane sodium movements with cells in chloride medium became downhill asymmetrical in nitrate medium, giving a net gain of cell sodium that was insensitive to ouabain and sensitive to furosemide. The drug thus partly retarded the gain of cell sodium that otherwise occurred in the somewhat leaky cells.
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PMID:The change from symmetry to asymmetry of a sodium transport system in red cell membranes. 285 58

Routine pharmacological screening of thiourea compounds led to the selection of pyridyl cyanoguanidines for their antihypertensive effects. From this cyanoguanidine class of compounds, P 1134 (pinacidil) was synthesised. Pinacidil has an asymmetrical carbon atom in the pinacolyl radical and the (-) enantiomer is more active than the (+) enantiomer both in vitro and in vivo. Pinacidil is rapidly absorbed following oral administration with the time to peak plasma concentration being 0.5 to 1 hour and, for the extended release formulation, 1 to 3 and 5 to 7 hours. The antihypertensive effect of pinacidil is proportional to the dose administered. Pyridine-N-oxide is the principal metabolite and accounts for approximately half of the dose excreted in the urine within 24 hours. In hypertensive rats and dogs, the blood pressure-lowering effect of pinacidil is dose-dependent and linearly related to the baseline blood pressure. The haemodynamic profile is characterised by an increased cardiac output as a consequence of increased stroke volume. An increase in heart rate follows the depressor response. The fall in blood pressure is preceded and superseded by a fall in the total peripheral resistance. Preclinical haemodynamic studies suggest that pinacidil is a directly acting precapillary vasodilator. The resting membrane potential of smooth muscle cells is approximately -60mV whereas the equilibrium potential for potassium is more negative, between -80 and -90mV. Pinacidil opens K+ channels and allows potassium to attain its equilibrium potential, resulting in hyperpolarisation of the cell at rest. A hyperpolarised cell is less prone to depolarisation, and without depolarisation there is no activation of the voltage-operated Ca2+ channels and, hence, no muscle contraction.
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PMID:Pinacidil. Preclinical investigations. 307 34


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