Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Onium Compounds”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 469 records · Page 26Linked to original sources
PubMed1984

Dissipation of membrane potential of Escherichia coli cells induced by macromolecular polylysine.

Macromolecular polylysine caused a rapid and drastic decrease in the membrane potential of Escherichia coli cells, monitored with the uptake of the lipophilic cation, tetraphenylphosphonium cation (TPP+). Respiration of cells was not affected to a significant extent by polylysine. Polylysine treatment induced the efflux of K+ from cells, suggesting that an increase in permeability of cytoplasmic membrane may be responsible for the decrease in the membrane potential. The action of polylysine is discussed in comparison with that of colicin E1 which is known to dissipate the membrane potential of E. coli cells.

Cell Membrane Permeability↗
PubMed1987

Relationship between the uptake and cytotoxicity of celiptium in wild type and resistant mutants of the bacterium Streptococcus pneumoniae.

Celiptium, a cationic and amphiphilic drug currently employed in cancer chemotherapy, was found to be accumulated against its concentration gradient by the bacterium Streptococcus pneumoniae. Accumulation was reduced in Celiptium resistant amiA mutants which were also observed to have reduced electric transmembrane potentials delta psi. This suggested a relationship between Celiptium toxicity and accumulation in S. pneumoniae, and indicated a delta psi - driven uptake in a manner reminiscent of that observed for other lipophilic cations such as tetraphenylphosphonium.

Alkaloids↗
PubMed1984

The inhibition of Ca uptake in cardiac membrane vesicles by verapamil.

Cardiac membrane vesicles take up Ca2+ in response to Na+ gradient (high inside) and negative inside membrane potential. Both components of the Ca2+ uptake, the Na+ gradient dependent uptake and the membrane potential dependent uptake are inhibited by verapamil; the action is dose-dependent and the concentrations of verapamil required to inhibit the Ca2+ uptake to 50% of its maximal value are 50 and 60 microM respectively. In the concentration ranges tested (50-750 microM Ca2+), the inhibitory effect of verapamil could not be antagonized by increasing the Ca2+ concentration of the medium. Introducing verapamil into the vesicles by rapid freezing and slow thawing of the vesicles had the same inhibitory effect as adding the same concentration of verapamil on the outside of the vesicles. Adding verapamil to both sides of the vesicle membrane led to higher inhibition of Ca2+ uptake. It is proposed that addition of verapamil can cause a change in cardiac membranes which is manifested by a decrease in the driving membrane potential and Ca2+ transport.

Animals↗
PubMed1985

Investigations of the action of the antitumour drug adriamycin on tumour cell membrane functions--I.

The membrane potential of L1210 murine leukemia cells was assessed by use of the tritiated lipophilic cation probe triphenylmethylphosphonium bromide. The potassium equilibrium potential of the cells was found to be -71 +/- 7 mV. The resting membrane potential was partly dissipated by the protonophore m-chlorocarbonylcyanidephenylhydrazone (10 microM), but was unaffected by ouabain (1 mM) and apparently by the calcium ionophore A23187 (2.5 microM). Monensin (20 microM) caused a hyperpolarization which, since it was blocked by ouabain, was presumed to be brought about by activation of the Na+K+-ATPase via an elevated cytoplasmic Na+ concentration. Adriamycin at concentrations as high as 5 X 10(-4) M brought about no change in the resting potential of the cells. Also, cytotoxic concentrations of adriamycin, unlike ouabain, had no effect on rubidium-86 transport into L1210 cells, nor upon a monensin-induced increased in rubidium-86 uptake. The results suggest that although adriamycin is capable of interaction with the plasma membrane, and may exert its cytotoxicity at this locus, changes in ion flux mediated by Na+K+-ATPase or those capable of changing the membrane potential do not appear to be implicated in its mechanism of action.

Animals↗
PubMed1988

Chronic administration of the oral hypoglycaemic agent diphenyleneiodonium to rats. An animal model of impaired oxidative phosphorylation (mitochondrial myopathy).

Daily subcutaneous administration of the oral hypoglycaemic agent, diphenyleneiodonium at a low dose (1.5 mg/kg body weight) over a 4-5 week period resulted in a normoglycaemic stable animal model of impaired oxidative phosphorylation in the rat. Diphenyleneiodonium specifically inhibits NAD-linked mitochondrial oxidation [Bloxham, Biochem. Soc. Trans. 7, 103 (1979)], and in isolated mitochondrial preparations from heart, soleus and gastrocnemius muscle and liver from treated animals NAD-linked respiration was reduced by 40% or more of mean control values. Brain and kidney mitochondria isolated from the treated group had similar rates of NAD-linked respiration to their respective control values. The activity of NADH-ferricyanide reductase was significantly reduced in all tissues tested, even in the isolated brain and kidney mitochondria where the activity in these tissues was 60-75% of control values. This suggests that at least 40% of Complex I activity must be inhibited before there is a decline in NAD-linked mitochondrial respiration. This paper discusses the use of diphenyleneiodonium as a means of establishing an animal model of the human disease state, termed mitochondrial myopathy.

Administration, Oral↗
PubMed1991

Effect of paracetamol on mitochondrial membrane function in rat liver slices.

The effect of paracetamol on mitochondrial function was studied using rat liver slices. Changes in the potential of the mitochondrial and plasma membrane were monitored using [3H]-triphenylmethylphosphonium (TPMP+) and [14C]thiocyanate (SCN-) probes, respectively. Liver slices were exposed to 10 mM paracetamol for various time periods (0-360 min) after loading with TPMP+. The release of TPMP+ which correlates with a decrease in the mitochondrial membrane potential became significant after 30 min incubation with 10 mM paracetamol. The change in the mitochondrial membrane potential was shown to be independent of cytochrome P450 activity. No significant change in plasma membrane potential was observed, until the release of lactate dehydrogenase (LDH) had begun, 4 hr after exposure, reflecting the ultimate stages of cell injury by paracetamol. These results suggest that paracetamol elicits a direct effect on the mitochondrial function before cell injury develops and adds further evidence to the role of mitochondria in paracetamol toxicity.

Acetaminophen↗
PubMed1992

Effect of depolarizing agents on the Ca(2+)-independent and Ca(2+)-dependent release of [3H]GABA from sheep brain synaptosomes.

The purpose of the present study was to compare the effects of several depolarizing agents on both the membrane potential and on the release of [3H] gamma-aminobutyric acid (GABA) from sheep brain cortex synaptosomes. We examined the effects of KCl, 4-aminopyridine (4-AP), veratridine, ouabain and tetraphenylphosphonium cation (TPP+) on Ca(2+)-independent (carrier-mediated) and Ca(2+)-dependent (exocytotic) release. We found that, in the absence of Ca2+, KCl at 40 mM releases 7.57 +/- 0.65%, veratridine at 50 microM releases 45.85 +/- 2.48%, ouabain at 1 mM releases 8.62 +/- 0.93% and TPP+ at 1 mM releases 4.09 +/- 0.37% of the total accumulated neurotransmitter, provided that the external medium contains Na+. These are about the maximal values of release obtained with each depolarizing agent in a Na+ medium and in the absence of Ca2+. Replacing external Na+ with choline blocks the release observed in the presence of the depolarizing agents in the absence of Ca2+, and this divalent ion can increase [3H]GABA release only for K+ or 4-AP. Synaptosomal depolarization requires Na+ except for K+ depolarization. Furthermore, although Ca2+ stimulates the release of [3H]GABA due to K+ depolarization (13.56 +/- 0.44%) or due to 4-AP (4.26 +/- 0.51%), it inhibits the release due to the other depolarizing agents. The amount of [3H]GABA released by 4-AP in Na+ medium (4.26 +/- 0.51%) is similar to that induced by KCl in the presence of Ca2+ in the absence of Na+ (3.39 +/- 0.29%) which represents only exocytotic release. This suggests that the Ca(2+)-dependent exocytotic release of [3H]GABA can be specifically induced by 4-AP in a Na+ medium, or by KCl in the absence of Na+, as reported by us earlier. The observation that Ca2+ inhibits the Ca(2+)-independent release is of interest because it suggests that Ca2+ may modulate the release of cytoplasmic GABA probably by inhibiting the carrier-mediated release of GABA. It is of interest as to whether Ca2+ regulation depends on intracellular Ca2+.

4-Aminopyridine↗
PubMed1992

Effects of chronic ethanol feeding on rat liver mitochondrial energy metabolism.

Chronic alcohol consumption is known to decrease hepatic mitochondrial respiration rate. It was shown here that the proton leak through the mitochondrial inner membrane was unaffected by chronic ethanol treatment. This indicates that changes in proton leak are not responsible for the alterations in respiration found in mitochondria isolated from ethanol-treated rats. Therefore, the lowered coupled respiration rate is solely due to a decrease in the activity of the electron transport chain. However, this alteration was only evident in coupled respiration (i.e. state 4) and was not apparent in uncoupled respiration. Thus, chronic ethanol treatment decreases the activity of the mitochondrial electron transport chain components which have control over coupled, but not uncoupled, respiration. Mitochondrial energy metabolism is regulated by thyroid hormone status. It was shown that the chronic alcohol treatment did not affect the circulating levels of thyroxine. Furthermore, the activity of mitochondrial alpha-glycerophosphate dehydrogenase, which is strongly affected by thyroid hormones, was unaltered by alcohol treatment. Thus, the effects of ethanol treatment on mitochondria occur independently of changes in circulating thyroid hormone levels.

Animals↗
PubMed1993

Differential effects of metabolic inhibitors on cellular and mitochondrial uptake of organic cations in rat liver.

The effects of several metabolic inhibitors on the uptake of tri-n-butylmethylammonium (TBuMA) were studied in isolated rat liver mitochondria, isolated rat hepatocytes and isolated perfused rat livers, in order to characterize further the mechanisms for carrier-mediated uptake and cellular accumulation of organic cations in the liver. Treatment of isolated hepatocytes with valinomycin, carbonylcyanide-m-chlorophenyl-hydrazone (CCCP), dinitrophenol, oligomycin or antimycin resulted in a rapid decrease in cellular ATP within 3 min of addition. The initial uptake rate of TBuMA was generally largely affected by these treatments. However, fructose at 10 mM had no effect at all on the uptake rate of the cation whereas cellular ATP was decreased to an extent comparable to that after treatment with the metabolic inhibitors. Consequently it was hypothesized that the metabolic inhibitors affected the initial cellular uptake rate of organic cations due to either altered intracellular sequestration (e.g. mitochondria) or alternatively to direct effects on the plasma membrane rather than by decreasing cellular ATP. Isolated rat mitochondria were shown to take up organic cations very efficiently. Accumulation in this organelle is probably driven by the negative membrane potential as measured by the uptake of the lipophilic cation [3H]tetraphenylphosphonium. Treatment of the isolated mitochondria with various metabolic inhibitors decreased the membrane potential in parallel to the effects on the uptake of TBuMA. Since mitochondria constitute a considerable intracellular volume, they may contribute largely to the storage of the organic cation in the hepatocyte. In isolated perfused livers, preloaded with either TBuMA or tetraphenylphosphonium (TPP+), the addition of valinomycin or CCCP leads to a marked backflux of the cations from the liver into the perfusion medium. This suggests strongly that a large part of the intracellular storage capacity is lost after metabolic inhibitor treatment, probably as the consequence of dissipation of the mitochondrial membrane potential. Since the metabolic inhibitors in contrast to TBuMA uptake did not decrease the initial uptake rate of TPP+ into isolated hepatocytes, it was concluded that mitochondrial uptake (mitochondria are the major storage sites for TPP+) is not an essential determinant of the initial uptake rate in intact hepatocytes.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗
PubMed1986

Characterization of glycine uptake in plasma membrane vesicles isolated from cultured glioblastoma cells.

C6 glioblastoma cells in culture were employed to isolate plasma membrane vesicles. After disruption of the glioblastoma cells by homogenization, membrane fractions were obtained by centrifugation on a discontinuous Ficoll density gradient. Fragmented membranes were found mainly in vesicular form. Transport of glycine has been demonstrated in membrane vesicles, using artificially imposed ion gradients as the sole energy source. The uptake of glycine is strictly dependent on the presence of Na+ and Cl- in the medium, and the process can be driven either by an Na+ gradient (out greater than in) or by a Cl- gradient (out greater than in) when the other essential ion is present. The process is stimulated by a membrane potential (negative inside) as demonstrated by the effect of ionophore valinomycin and anions with different permeabilities. The kinetic analysis shows that glycine is accumulated by two systems with different affinities.

Biological Transport↗
PubMed1986

Regulation of voltage-dependent Ca2+ channels of neuronal cells by chronic changes in membrane potential.

The regulation of voltage-dependent Ca2+ channels by chronic changes in membrane potential was studied by measuring the binding of [3H]nitrendipine to membranes from PC12 pheochromocytoma cells. Depolarization of the cells by elevation of extracellular K+ caused up to a 45% loss of [3H]nitrendipine binding sites within 4 days without any change in Kd. Repolarization of the cells caused a return to control binding within 1-2 days, showing that either decreases or increases in membrane potential can cause reversible changes in [3H]nitrendipine binding sites.

Animals↗
PubMed1990

Synaptic aging as revealed by changes in membrane potential and decreased activity of Na+,K(+)-ATPase.

Age-related changes in the membrane potential of nerve terminals were investigated by monitoring the accumulation of tritium-labeled triphenylmethylphosphonium ion, [3H]TPMP+, in mouse cortical synaptosomes. The resting membrane potential became less negative with advancing age, that is, it changed from -64.5 +/- 0.8 to -58.1 +/- 2.3 mV between 6 and 27 months of age. The intrasynaptosomal potassium concentration was found to decrease concomitantly by 13% in aged mice (56.6 +/- 0.9 mM) as compared to young-adult mice (64.9 +/- 0.5 mM). The ouabain-sensitive Na+,K(+)-ATPase activity of synaptic plasma membranes decreased in late senescence to 82% of the adult level. To examine the correlation with the decreased Na+,K(+)-ATPase activity, the membrane lipid composition was analyzed. Among the membrane phospholipids, only the content of phosphatidylcholine decreased in the course of senescence. The changes in the Na+,K(+)-ATPase activity were found to be positively correlated with the changes in the phospholipid content, and more specifically with the changes in the phosphatidyl-choline content. These results suggest that age-related alterations in the microenvironment constructed by phospholipids may decrease the activity of Na+,K+-ATPase, resulting in neuronal ion imbalance and decreased membrane potential. This might be responsible in part for altered functions of nerve terminals in aging brain.

Aging↗
PubMed1993

Temporal and spatial preferences of c-fos mRNA expression in the rat brain following cortical lesion.

The expression of the proto-oncogene c-fos is increased in neuronal cells by a number of stimuli and the usefulness of this gene as a marker of neuronal activity has been demonstrated. The temporal and spatial expression of c-fos mRNA following the induction of a unilateral cortical lesion have been investigated in the rat brain by Northern blot analysis and in situ hybridization histochemistry. It was observed that the lesion evoked a rapid increase (20-fold) in the content of c-fos mRNA in the ipsilateral cortex, whereas in the contralateral cortex c-fos mRNA expression was more modest (7-fold). In the whole hippocampus a large and very rapid increase (17-fold) of c-fos mRNA expression was detected. The effect of a cortical lesion on Ca2+ uptake and membrane potential was also investigated. Using synaptosomes as a model system, we have provided evidence that Ca2+ entry via membrane depolarization increases in coordination with c-fos gene expression in neuronal cells. The principal conclusions from this study are that cortical lesions induce transient expression of the c-fos gene in specific neuronal cells of the rat brain.

Animals↗