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Biomedical subjects

A Egyed

Publications and source records attributed to A Egyed.

15 recordsLinked to original sources
PubMed1997

The mechanism of action of alpha 2 adrenoceptor blockers as revealed by effects on open field locomotion and escape reactions in the shuttle-box.

The precise mechanism of action of alpha 2 adrenoceptor blockers in not known, although in principle they have two main effects: (i) they stimulate the norepinephrinergic system by inhibiting the negative feed back of norepinephrine release (presynaptic effect) and (ii) they inhibit the effects of norepinephrine on postsynaptic alpha 2 adrenoceptors. We postulate that if the presynaptic actions of the antagonists prevail, the enhanced norepinephrine release leads to an activation of postsynaptic alpha 1 or beta adrenoceptors. In this case the effects of alpha 2 adrenoceptor blockers can be reversed by antagonists acting on the latter two adrenoceptors, since postsynaptic alpha 2 adrenoceptors are also blocked. If the postsynaptic blockade of alpha 2 adrenoceptors is the main cause of effects, than the blockade of alpha 1 or beta adrenoceptors should not reverse the action of alpha 2 blockers. The alpha 2 blocker idazoxan (dose 0.5-5 mg/kg) increased locomotor activity in an open field, an effect that was abolished by both alpha 1 and beta receptor blockers (prazosin and propranolol, respectively). Escape responses in a shuttle box were strongly suppressed by idazoxan (0.5-2 mg/kg). However, this effect was not changed by concomitant alpha 1 or beta receptor blockade. These results suggest that the mechanism of action of alpha 2 adrenoceptor blockers depends on which effects are studied. Exploration seems to be affected by a presynaptic mechanism as neurons bearing postsynaptic alpha 1 or beta adrenoceptors are involved in the control of this behavior, while escape reactions appear to be affected by the postsynaptic blockade of alpha 2 adrenoceptors (i.e. neurons bearing postsynaptic alpha 2 adrenoceptors are involved in its control). Thus, there is no generalized mechanism of action for alpha 2 adrenoceptor blockers; their precise mode of action should be investigated in each particular case.

Adrenergic alpha-2 Receptor Antagonists↗
PubMed1996

Protection against non-NMDA receptor-mediated excitotoxicity by GYKI 52466 in mature telencephalic cultures of the rat.

The neuroprotective effect of 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride (GYKI 52466), a recently developed non-competitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/kainate antagonist was demonstrated against quisqualate (10 or 15 microM) and AMPA (20 microM) excitotoxicity in mature (17-20 days in vitro) cultures of rat embryonic telencephalic cells. GYKI 52466 attenuated quisqualate (15 microM) or AMPA (20 microM) neurotoxicity in a dose-dependent manner with IC50 of 16 microM and 10 microM, respectively.

Animals↗
PubMed1991

Na+ modulates carrier-mediated Fe2+ transport through the erythroid cell membrane.

The effects of univalent cations on Fe2+ uptake by rabbit reticulocytes have been studied. The rate of Fe2+ uptake was almost identical when measured in Na(+)-free choline chloride or KCl medium. Na+ but not Li+ inhibited Fe2+ uptake even at relatively low concentrations (2.5-20 mM) in these media. In contrast to this effect of extracellular Na+, the rate of Fe2+ uptake was facilitated by an increase in the intracellular Na2+ concentration in the range 5-40 mM, suggesting that intracellular Na+ is required for the uptake process. This effect also appears to be specific for Na+. Amiloride inhibited Fe2+ uptake in KCl (or in choline chloride), but had little if any effect in NaCl. Therefore a Na(+)- and amiloride-sensitive and a Na(+)- and amiloride-insensitive component can be distinguished. The two components differ in maximum velocity and pH optimum, but not in their apparent affinity for Fe2+. The ineffectiveness of selective inhibitors excludes the involvement of the Na+/H+ or Na+/Ca2+ exchange mechanisms. To account for the results presented in this work, a Na+/Fe2+ exchange system in the erythroid cell membrane is proposed.

Amiloride↗
PubMed1988

Carrier mediated iron transport through erythroid cell membrane.

The transport of iron through erythroid cell membrane was studied in a model system, measuring ferrous iron uptake by reticulocytes. It was found that these cells were able to take up ferrous iron and to incorporate it into haem at a rate similar to that observed when diferric transferrin was the iron donor. No comparable iron uptake could be measured when the metal was provided as Fe3+-citrate or when reticulocytes were replaced by mature erythrocytes. The involvement of endogenous transferrin in the Fe2+ uptake by reticulocytes could be excluded, since proteolytic treatment of the cells had no significant effect on the process. Fe2+ uptake by reticulocytes followed saturation kinetics, characteristic to carrier mediated transport processes. Kinetic analysis of the data revealed the following apparent transport parameters: Km = 8.8 +/- 3.8 microM; Vmax = 1.1 +/- 0.2 ng/10(8) reticulocytes/min. These results indicate that a high affinity, carrier mediated iron transport system is present in the reticulocyte membrane, ensuring the efficient translocation of the metal through the membrane barrier between the site of its release from transferrin and the site of its utilization.

Animals↗
PubMed1986

Coated pit formation: a membrane function involved in the regulation of cellular iron uptake.

Diferric-transferrin induces a marked increase in the number of coated pits on the reticulocyte membrane. This increase is followed by a decline, often to below the initial number. Since a good correlation was found between the rate of iron uptake and the number of coated pits, but not between the rate of transferrin recycling and the coated pit count, it is likely that coated pit formation is necessary for the removal of iron from transferrin. The decline in the number of transferrin-induced coated pits was observed only when haem synthesis was undisturbed, indicating that the accumulation of intracellular haem inhibits coated pit formation. Based on these results we suggest that haem regulates the rate of iron uptake by inhibiting iron removal rather than receptor recycling.

Animals↗
PubMed1986

A comparative study on the cellular processing of free and gold-conjugated transferrin.

The kinetics of the transferrin-reticulocyte interaction was studied using free and colloidal gold-conjugated double labelled transferrin (Tf and AuTf, respectively). Simultaneous biochemical and morphological experiments provided the following information: 1. The cellular recycling of Tf is significantly faster than that of AuTf. 2. AuTf induces a marked increase in the number of multivesicular elements (MVE) in rabbit reticulocytes. 3. The release of AuTf from the cells is very slow and accumulation of gold particles in MVEs can be observed during the process. The results suggest that the two postulated pathways of the transferrin-cell cycle (a fast, iron-donating and a slow, receptor-shedding cycle) are not similarly involved in the cellular processing of Tf and AuTf. While it has been suggested that in the Tf-cell interaction the fast recycling mechanism is dominating, it is likely that, probably due to steric effects, the majority of AuTfs are forced into the slower receptor-shedding pathway. These observations call attention to the possible limitations of the colloidal gold labelling technique in the determination of the kinetics and pathway of intracellular processing of free ligands.

Animals↗
PubMed1985

Erythrocyte enzyme allotypes in the X-linked recessive disorders, Duchenne muscular dystrophy and haemophilia-A hemizygotes and heterozygotes.

The erythrocyte enzyme-systems acid phosphatase, phosphoglucomutase, glutamate pyruvate transaminase, adenosine desaminase, adenylate kinase, glyoxase, glucose-6-phosphate dehydrogenase and esterase-D-isoenzyme phenotypes were studied for their percentile distribution and were compared with their incidence in the diseases with X-linked recessive heredity, Duchenne muscular dystrophy (DMD) and haemophilia-A, in hemizygous male children and heterozygous mothers. Considering the frequency distribution of the above mentioned isoenzyme phenotypes of the enzyme-systems in DMD, the phenotypes proved to be homogeneous, only the X transmitted 6-phosphogluconate dehydrogenase (6-PGD) isoenzyme types were found to be genetic markers in DMD hemizygotes and heterozygotes. In these genotypes the 6-PGD A phenotype showed a decrease while the phenotypes 6-PGD AB and B were significantly increased. The adenylate kinase (AK) 2-1 isoenzyme phenotype was increased to 25% against the population frequency of 6.34%, while the AK 1-1 phenotype occurred in 75% against its population frequency of 93.59%, showing a significantly decreasing tendency in haemophilia-A hemizygotes and heterozygotes.

Acid Phosphatase↗
PubMed1984

Availability, distribution and kinetics of the transferrin receptors of rabbit reticulocytes.

The binding of transferrin by reticulocytes was studied at 3 degrees C and 37 degrees C. It was demonstrated that 50% of the total number of receptors are in an exposed position on the outer side of the plasma membrane and 50% of them are in a masked position. All of the receptors can take either of the positions. The transition between these positions is temperature dependent and can be observed as the progressive phase of the transferrin binding. It is suggested that the transferrin receptors are in dimers, one of the subunits being in the exposed position the other in the masked position. The subunits change position simultaneously. This movement of the receptors is independent of the presence of transferrin. In the light of these results a new model for transferrin-cell cycle is proposed.

Animals↗
PubMed1983

Studies on the partition of transferrin-donated iron in rabbit reticulocytes. II. Distribution and kinetics of non-haem iron in cytosol.

Reticulocytes with high cytosolic non-haem radioiron content were prepared by adding metabolic inhibitors. The cells were then reincubated without the inhibitors for various periods of time. Cytosol was prepared from the labelled cells and fractionated on a Sephadex G-100 column on which four main non-haem radioiron containing peaks could be distinguished. During reincubation the 59Fe content of these cytosol fractions changed in different ways. The high molecular weight fraction showed little metabolic activity, indicating that this fraction is not utilized for haem synthesis when iron is in excess in the cytosol. The second non-haem radioiron containing peak eluted with the haemoglobin moiety. It was clearly distinct from transferrin and could be separated from haemoglobin. This non-haem iron binding substance proved to be rather stable: 1 mM EDTA could not remove a significant amount of iron from it. During reincubation its radioiron content decreased almost linearly with time. Two further peaks eluted in the low molecular weight region. Their kinetics during reincubation suggest that these peaks represent those non-haem iron components of the cytosol which can reversibly move from the cytosol into the stroma compartment.

Animals↗
PubMed1982

Studies on the partition of transferrin-donated iron in rabbit reticulocytes. I. The kinetics of iron distribution between stroma and cytosol.

The distribution of transferrin-donated iron between the stroma and cytosol compartments of rabbit reticulocytes was studied. In cells with inhibited haem synthesis iron accumulates in the stroma fraction. The stromal accumulation of iron was found to be reversible and dependent on the coupled state of mitochondrial respiration. Iron in cytosol, however, proved to be more available for haem synthesis than iron accumulated in stroma. A hypothesis concerning mitochondrial iron uptake is proposed, by which the experimental and pathological changes in the intracellular distribution of iron can be explained.

2,4-Dinitrophenol↗
PubMed1980

Transferrin-bipyridine iron transfer mediated by haemoproteins.

Rabbit reticulocyte cytosol was able to mediate transferrin-bipyridine iron transfer in the presence of ATP. The cytoplasmic factor responsible for the mediation of iron transfer was identified as haemoglobin. Other cytoplasmic proteins and the membrane fraction were ineffective. Human alpha and beta subunits and human myoglobin were over three times more effective than human haemoglobin A. Carbon monoxide strongly inhibited the mediation of iron transfer. Oxidation of haemoglobin abolished it but methaemoglobin could be reactivated with NADH, even when azide was bound to the haem iron. Neither globin nor haem alone were able to mediate iron transfer, even when NADH was present. Together, the reconstituted methaemoglobin A could be reactivated wtih NADH. Although the physiological significance of this pehnomenon is not clear, the involvement of haemoproteins in intracellular iron metabolism seems likely.

2,2'-Dipyridyl↗
PubMed1975

Effect of adenine nucleotides and pyrophosphate on the exchange of transferrin-bound carbonate.

1. ATP, ADP and pyrophosphate accelerate the exchange of carbonate of the transferrin-iron-carbonate ternary complex, while AMP, cyclic AMP and phosphate have no effect. 2. ATP promotes carbonate exchange without removing iron from transferrin, whereas pyrophosphate effectiely attacks both the anion and iron components of the ternary complex. 3. Transferrin readily takes over iron from its ATP or pyrophosphate complex. 4. Neither ATP nor pyrophosphate can substitute for carbonate of the ternary complex. These results fit in well with the concept that ATP may play a direct role in the iron uptake by reticulocytes.

Adenine Nucleotides↗