Biomedical subjects

A Eichinger

Publications and source records attributed to A Eichinger.

22 records · Page 2Linked to original sources

PubMed1985

Comparison of benzodiazepine receptor binding in membranes from human or rat brain.

Specific high affinity binding of [3H]flunitrazepam to membranes from human brain was stimulated by gamma-aminobutyric acid (GABA), pentobarbital, 1-ethyl-4-(isopropylidene-hydrazino)-1H-pyrazolo[3,4b]pyridine-5-carboxy lic acid ethyl ester hydrochloride (SQ 20009) and avermectin B1a and was unaffected by 2 microM 4'-chlorodiazepam (Ro 5-4864) indicating that [3H]flunitrazepam in human brain as well as in rat brain predominantly binds to benzodiazepine receptors specific to brain, which was associated with a GABA receptor and several modulatory binding sites for drugs. The potency of several selective and non-selective ligands for benzodiazepine receptors for inhibition of the binding of [3H]flunitrazepam was compared in membranes from human or rat brain cerebellum, hippocampus and cerebral cortex. It was demonstrated that all these compounds, derived from different chemical structures, had a remarkably similar potency for inhibition of the binding of [3H]flunitrazepam in the corresponding regions of the human or rat brain. However, irreversible labelling of benzodiazepine binding sites with [3H]flunitrazepam and subsequent SDS-polyacrylamide gel electrophoresis and fluorography revealed more photolabelled protein bands in human than in rat cerebellum and hippocampus. The results seem to indicate that, although the pharmacological properties of reversible binding of [3H]flunitrazepam are remarkably similar in membranes from rat or human brain, the molecular heterogeneity of benzodiazepine binding sites is even greater in human than in rat brain.

Animals↗

PubMed1985

Differential degradation of different benzodiazepine binding proteins by incubation of membranes from cerebellum or hippocampus with trypsin.

When rat brain membranes were incubated with [3H]flunitrazepam in the presence of UV light, predominantly one protein (P51) was irreversibly labeled in cerebellum and at least two proteins (P51 and P55) were labeled in hippocampus. On digestion of membranes with increasing concentrations of trypsin up to 40% of radioactivity irreversibly bound to proteins was removed from the membranes. In addition, P51 was nearly completely degraded to a peptide with apparent molecular weight 39,000 and this peptide was further degraded to a peptide with apparent molecular weight 25,000. In contrast, protein P55 was only partially degraded by trypsin and yielded two proteolytic peptides with apparent molecular weights 42,000 and 45,000 which seemed to be rather stable against further attack by trypsin. Membranes treated with trypsin still had the capacity to bind [3H]-flunitrazepam reversibly with an affinity similar to that of membranes not previously treated with trypsin. When these membranes were irradiated with UV light, the same proteolytic peptides were detected as in membranes first photolabeled and then digested with trypsin. These results suggest a close association between reversible and irreversible benzodiazepine binding sites and indicate that membrane-associated proteins P51 and P55 are differentially protected against degradation by trypsin.

Affinity Labels↗

PubMed1984

Photoaffinity labeling of different benzodiazepine receptors at physiological temperature.

Irreversible labeling of benzodiazepine receptors in membranes from cerebellum or hippocampus was compared at 0 degrees C using [3H]flunitrazepam as a photoaffinity ligand. [3H]Flunitrazepam reproducibly and irreversibly labeled mainly one protein (P51) in cerebellum and at least two proteins (P51 and P55) in hippocampus at both temperatures. Differential inhibition at 37 degrees C of irreversible [3H]flunitrazepam binding to the individual proteins by several selective benzodiazepine receptor ligands supports the hypothesis that P51 and P55 are associated with different benzodiazepine receptors.

Affinity Labels↗

PubMedDate not supplied

Protective effect of vitamin E in a rat model of focal cerebral ischemia.

Under certain pathological conditions such as cerebral ischemia and reperfusion the occurrence of free radicals is remarkably increased. However, only very little information is available on their quantitative relevance for the pathophysiology and final outcome of diseases. The aim of the present study was to evaluate the contribution of oxygen radicals in the pathogenesis of a stroke. For this purpose a rat model for stroke was used. Two of three vitamin E deficient groups were repleted with different dosages of DL-alpha-tocopherylacetate. No signs of vitamin E deficiency could be observed. However, the weight gain during repletion was increased in the vitamin E repleted groups. Brain infarction was created by occlusion of the right middle cerebral artery (MCAO) for two hours. After 24 hours the measurements of infarct volumes were taken. The infarct volume of the group with the highest repletion dosage was significantly reduced by 81%. This was also expressed in a higher rate of gait disturbances after MCAO of the deficient animals. The control of vitamin E status exhibited a similar repletion-dependent level in plasma and brain. These results strongly support the hypothesis that the generation of oxygen radicals occurring during reperfusion is an important aspect of the pathophysiological mechanism in brain infarction.

Animals↗