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Biomedical subjects

G Ebinger

Publications and source records attributed to G Ebinger.

At least 127 records · Page 7Linked to original sources
PubMed1988

Autoradiographic localization of D1 and D2 dopamine receptors in the human brain.

The distribution of dopamine D1 and D2 receptors in several human brain regions was investigated using autoradiography with the radioligands [3H]SCH 23390 and [3H]spiroperidol. The highest densities of both dopamine receptor types are seen in the nucleus caudatus, putamen and nucleus accumbens. Whereas the density of the D2 receptors is similar in the two segments of the globus pallidus, the pars medialis of the globus pallidus contains a three-fold higher concentration of D1 receptors than the pars lateralis. D1 and D2 receptors are present in the amygdala and substantia nigra. Both receptor types are absent in the cerebellum. The thalamus contains low densities of D1 receptors but no D2 receptors. Only D2 receptors are seen in the anterior lobe of the pituitary gland. The whole cerebral cortex is rich in D1 receptors, while D2 receptors, in low concentrations, are confined to the entorhinal area and cingulate cortex.

Aged↗
PubMed1988

D1 dopamine receptors in human putamen, frontal cortex and calf retina: differences in guanine nucleotide regulation of agonist binding and adenylate cyclase stimulation.

High-affinity binding sites for the D1 dopamine receptor antagonist [3H]SCH 23390 were identified in membranes from human putamen, frontal cortex and calf retina. In frontal cortex binding not only occurred to D1 but also to 5-HT2 receptors. In retina and putamen no binding to 5-HT2 receptors was detected. All further binding experiments in frontal cortex were carried out in the presence of 20 nM mianserin to prevent binding to 5-HT2 receptors. In the 3 tissues, antagonist competition curves were monophasic, whereas competition curves with the agonist dopamine revealed the presence of two binding sites, one having high affinity (RH) (32% in retina, 28% in putamen, and 15% in frontal cortex) and the other having low affinity (RL). In retina, the addition of 100 microM GTP caused a full conversion of RH into RL. In contrast, in frontal cortex, RH sites were not altered by 400 microM GTP or 100 microM 5'-guanylyl-imidodi-phosphate (Gpp(NH)p). In putamen, both guanine nucleotides provoked only a partial conversion of RH into RL. Dopamine (100 microM) produced a 220% and 56% increase in cAMP production in respectively retina and putamen homogenates, while no increase was observed in frontal cortex homogenate. These data may suggest that not all D1-receptors are coupled to the adenylate cyclase system.

Adenylyl Cyclases↗
PubMed1988

Subtypes of adrenergic and dopaminergic receptors in bovine cerebral blood vessels.

Binding of the radiolabelled antagonists [3H]rauwolscine, [3H]SCH 23390 and (-)-[3H]dihydroalprenolol revealed the presence of alpha 2-adrenergic greater than DA1 dopaminergic greater than beta-adrenergic receptors in membrane preparations of calf basal cerebral arteries (basilar artery and circle of Willis) and pial vessels of the cerebral convexity. Computer-assisted analysis of ICI 118 551/(-)-[3H]dihydroalprenolol competition binding curves indicated the existence of beta 1- and beta 2-adrenergic receptor subtypes (beta 2/beta 1 ratio 7:3). No specific binding of [3H]prazosin (to alpha 1-adrenergic receptors) and [3H]spiroperidol (to DA2 dopaminergic receptors) was detected. Whereas DA1, beta 1- and beta 2-receptor densities were very similar in both blood vessel types, the alpha 2-receptor density was 3-fold higher in the pial vessels of the convexity. This suggests a functionally more important vasoconstrictor adrenergic control of the cerebral circulation in pial vessels of the convexity than in the arteries at the base of the brain.

Animals↗
PubMed1988

Identification of D1-like dopamine receptors on human blood platelets.

Dopamine is able to inhibit the epinephrine-induced aggregation of human blood platelets, but the mechanism of action has not been elucidated. In this study we report that membranes from human blood platelets possess high affinity, saturable and stereoselective binding sites for the D1 dopamine receptor antagonist (3H) SCH 23390. (3H) SCH 23390 appeared to label a single class of binding sites with a Bmax of 18.6 +/- 1.6 fmol/mg protein and a KD of 0.8 nM. The potencies of different dopaminergic antagonists and agonists in displacing (3H) SCH 23390 from blood platelet membranes were similar to those obtained for striatal membranes. Unlike the classically defined D1 receptors, e.g. those in striatum, the D1 receptor sites on platelets appeared not to be coupled to the adenylate cyclase system, hence the term "D1-like". The D1 agonist SKF 38393 was more potent than dopamine in inhibiting platelet aggregation induced by epinephrine, and the effects of dopamine and SKF 38393 were prevented by SCH 23390. These results suggest that the inhibitory action of dopamine on the epinephrine-induced platelet aggregation is mediated through these D1-like receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1988

Characterization of M1- and M2-muscarinic receptors in calf retina membranes.

Muscarinic receptors are identified in bovine retina membranes by the specific binding of 1-[benzilic-4,4'-3H]-quinuclidinyl benzilate [3H]-QNB. Binding occurs to one population of non-cooperative binding sites: KD = 0.11 +/- 0.02 nM and Bmax = 0.61 +/- 0.07 pmol/mg protein. Competition binding curves of the M1-selective antagonist pirenzepine are shallow. Computer-analysis reveals the presence of 45 +/- 1% M1-receptors (high affinity sites for pirenzepine, Ki = 31 +/- 10 nM). The remaining low affinity sites (Ki = 1.0 +/- 0.3 microM) are denoted as M2-receptors. Competition binding curves with the agonist carbachol are shallow as well. 1 mM GTP causes a rightward shift and a steepening of the carbachol curve, whereas 1 mM N-ethylmaleimide (NEM) provokes a leftward shift and also a steepening of the curve. The GTP effect is abolished by NEM. Binding of the antagonists [3H]-QNB, atropine or pirenzepine is not modulated by GTP nor by NEM.

Animals↗
PubMed1988

Recurrent forms of sporadic brachial plexus neuropathy. A report of two cases.

Two patients presenting a relapsing form of sporadic brachial plexus neuropathy, the so-called Parsonage Turner syndrome, are reported. The diagnosis is based on clinical and electromyographic features. Recurrent attacks, although infrequently encountered, have been well described in the past. Sporadic cases of this syndrome must be differentiated from the familial varieties of neuralgic amyotrophy in which, two main subgroups of patients are distinguished: those showing facial dysmorphic features and those with findings of a tomaculous neuropathy predisposing them to pressure palsies. Apart from the obvious difference as regards familial occurrence, the familial and non-familial varieties of neuralgic amyotrophy differ in a number of respects: associated congenital defects, early age of onset and high rate of recurrence in the former. Finally some possible pathogenetic mechanisms of the syndrome are briefly reviewed.

Adult↗
PubMed1987

Different agonist binding properties of M1 and M2 muscarinic receptors in calf brain cortex membranes.

The muscarinic antagonist 1-[benzilic 4,4'-3H]-quinuclidinyl benzilate [3H]-QNB) bound to a single class of non-cooperative sites in calf cerebral cortex membranes (KD = 0.29 nM and Bmax = 1.06 pM/mg protein). Computer-assisted analysis of the shallow pirenzepine/[3H]-QNB competition binding curves indicated that 68% of these sites were of the M1-subtype and the remaining 32% of the M2 subtype. Respective Ki-values for pirenzepine were 27 nM and 1.14 microM. Binding characteristics of the antagonist atropine and of the agonist carbachol for M2 were evaluated by performing competition binding with 0.5 nM [3H]-QNB in the presence of 2 microM pirenzepine. The binding characteristics for the M1 receptors were obtained indirectly by subtracting the curve for M2 from the total curve, or directly by competition binding with 0.3 nM [3H]-pirenzepine. Atropine competition curves were steep for M1 and M2 and were not affected by 1 mM GTP nor by 1 mM N-ethylmaleimide. The carbachol competition curve was shallow for M2. The steep curves for M1 indicate that this receptor subclass was only composed of low agonist affinity sites. GTP, which caused a rightward shift and a steepening of the carbachol competition curve for M2, did not affect the curves for M1. N-ethylmaleimide provoked a leftward shift and a steepening of the carbachol competition curve for M2 and abolished GTP modulation. A leftward shift was also observed for M1, but of a smaller magnitude (i.e. 3-4-fold for M1 compared to 17-fold for M2). These data suggest that, in calf brain cortex, M1 and M2 receptors show different susceptibility towards GTP and N-ethylmaleimide modulation.

Animals↗
PubMed1987

Combined ion-pair extraction and high-performance liquid chromatography for the determination of the biogenic amines and their major metabolites in single brain tissue samples.

A combined procedure based on reversed-phase liquid chromatography with electrochemical detection has been developed for the determination in the picomole range of the monoamines dopamine, norepinephrine, epinephrine and serotonin, and their major metabolites 3,4-dihydroxyphenylacetic acid, homovanillic acid, 3-methoxy-4-hydroxyphenylethylene glycol, 5-hydroxyindoleacetic acid, normetanephrine, metanephrine and 3-methoxytyramine. Sample pretreatment consists of the extraction of the neutral and acidic metabolites with ethyl acetate, followed by the extraction into heptane of the catecholamines with tetraoctylammonium bromide as counter-ion in the presence of diphenylborate. The residual supernatant is directly injected in the chromatographic system for quantification of serotonin, normetanephrine, metanephrine and 3-methoxytyramine.

Biogenic Amines↗
PubMed1987

Torsade de pointes as a complication of brainstem encephalitis.

A case of brainstem encephalitis complicated by torsade de pointes is described. The possible occurrence of ventricular arrhythmias may contribute to the mortality in this condition. We recommend the admission of patients with brainstem encephalitis to an intensive care unit, for a period of electrocardiographic monitoring.

Adult↗
PubMed1987

Rhabdomyolysis in hypokalaemic periodic paralysis: a clue to the mechanism that terminates the paralytic attack?

The changes in serum levels of myoglobin (Mb) and creatine kinase (CK) during a spontaneous attack of hypokalaemic periodic paralysis were studied. During paralysis, serum Mb and CK were normal. A rise in plasma potassium, resulting in clinical recovery, was associated with a simultaneous rise in serum Mb, and followed by a rise in serum CK. It is postulated that hypokalaemia might cause muscle ischaemia, which would result in an accumulation of free fatty acids (FFA) within the muscle cells. High concentrations of FFA may induce molecular changes and increase the permeability of the sarcolemma. This might be the mechanism by which potassium is released from muscle cells into the circulation and muscle membrane excitability is restored.

Adult↗
PubMed1987

Muscarinic cholinergic receptor subtypes in normal human brain and Alzheimer's presenile dementia.

Brain muscarinic M1 and M2 binding sites, as defined by their affinity for pirenzepine, were studied in 24 regions of 3 normal control brains. For each region, the binding of [3H]QNB, a non-subtype selective antagonist, was saturable with a mean KD of 0.117 +/- 0.066 nM. Computer-assisted analysis of the pirenzepine competition binding curves yielded the amount of high affinity (M1) and low affinity sites (M2) as well as their respective Ki values for this ligand. The neocortex contained a mixed population of 67% M1 and 33% M2 sites, without locoregional heterogeneity. The muscarinic receptors of the caudate nucleus, putamen, pallidum, hippocampus and nucleus amygdalis were predominantly of the M1 type as well. The cerebellum and the brain-stem are examples of regions containing over 90% M2 sites. White matter structures like the centrum ovale appeared to contain low concentrations of [3H]QNB binding sites, predominantly of the M1 subtype. The data for the frontal cortex were compared with data obtained in 3 patients who died from Alzheimer's disease with very early onset: the muscarinic receptor concentrations were somewhat lower but their M1/M2 ratio remained unchanged. GTP caused an appreciable rightward shift and steepening of the carbachol competition binding curve in M2 predominant regions such as the pons, whereas only a slight shift was observed in the cortex. In the presence of GTP, the alkylating reagent N-ethylmaleimide caused a 35-fold increase of the affinity for carbachol in M2 predominant regions. In contrast, regions where the receptors are predominantly of the M1 type, N-ethylmaleimide caused only a 5-fold increase in agonist affinity. These findings confirm our previously formulated hypothesis that the ability of N-ethylmaleimide to modulate the agonist affinity is an additional criterion for the characterization of M1 and M2-type receptors.

Adult↗
PubMed1987

Distribution of biogenic amines and their catabolites in brains from patients with Alzheimer's disease.

Norepinephrine, epinephrine, dopamine, serotonin and their major catabolites were measured in 17 regions of the left hemisphere of two brains obtained from two brothers with Alzheimer's disease with very early onset. The clinical diagnosis was confirmed by histological examination of the right hemispheres and brain stems. The quantitative data were compared with our values in normal brains. In the patient suffering from the less severe dementia, there was a severe reduction of the serotonin concentration in all examined neocortical areas and its concentration was even below the detection limit in the nucleus amygdalis, hippocampus, caudate nucleus, putamen, globus pallidus and substantia nigra. In the other patient, who suffered from a more pronounced dementia with myoclonus, the serotonin concentration was below the detection limit in all examined structures. In contrast with these findings, the noradrenergic, adrenergic and dopaminergic systems appeared to be relatively unaffected by the disease process. Focusing our attention on the nuclei wherein the monoamine transmitter systems originate, it appeared that neuronal losses and neurofibrillary tangles clearly predominated in the substantia grisea subependymalis, the nucleus centralis superior and the nucleus raphe dorsalis, origin of the main serotonergic system. The serotonin deficiency sheds light on possible mechanisms of myoclonus in Alzheimer's disease.

Adult↗
PubMed1987

Simultaneous determination of levodopa, carbidopa, 3-O-methyldopa and dopamine in plasma using high-performance liquid chromatography with electrochemical detection.

An analytical method is described which allows a fast, reliable and precise determination of levodopa and its metabolises 3-O-methyldopa and dopamine, as well as the peripheral aromatic amino acid decarboxylase inhibitor carbidopa, in a single 1 ml plasma sample of Parkinsonian patients. The compounds are quantitatively isolated on small Sephadex G-10 columns and determined by HPLC with electrochemical detection. Dihydroxybenzylamine or alpha-methyldopa are used as the internal standard. An example of therapeutic drug monitoring in a patient with fluctuations in motor performances is given. It is confirmed that interference with absorption of levodopa from the stomach by food can be partly responsible for these observed fluctuations.

Journal Article↗
PubMed1987

The significance of homovanillic acid and 3,4-dihydroxyphenylacetic acid concentrations in human lumbar cerebrospinal fluid.

The concentrations of the acidic dopamine (DA) catabolites homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) measured in human CSF are supposed to reflect the "turnover" of DA in the brain. The notion of "turnover" is, however, not synonymous with impulse nerve activity in the dopaminergic systems. Significant amounts of DOPAC and HVA could, indeed, be demonstrated in brain structures wherein dopaminergic innervation has not been documented. It must also be noted that DA is not only a neurotransmitter itself, but also a precursor of norepinephrine and epinephrine. Furthermore, in lumbar CSF, levels of biogenic amine catabolites partially reflect metabolism in the spinal cord and may have limited relevance to neurotransmission in the brain. To elucidate these points further, we determined the concentrations of DOPAC and HVA in 22 areas of six human brains and eight levels of six human spinal cords. The data were correlated with the concentration of DA. Quantitative determinations were done using HPLC with electrochemical detection, after solvent and ion-pair extraction. In this study, significant amounts of both DOPAC and HVA were demonstrated in brain structures not previously associated with dopaminergic innervation. The relatively lower DA concentration in these structures suggests that in these regions, the DOPAC and HVA concentrations are unrelated to dopaminergic neurotransmission. The possible role of capillary walls and glial cells in the catabolism of DA must be further evaluated. The demonstration of DOPAC and HVA in the spinal cord is another argument against the hypothesis that CSF levels of HVA and DOPAC reflect closely the activity of the dopaminergic systems in the brain.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

Hormonal changes during a spontaneous attack of hypokalemic periodic paralysis.

We studied the hormonal changes during a spontaneous attack of hypokalemic periodic paralysis in a 20-year-old man, before and after treatment with potassium chloride. During paralysis, we observed high circulating levels of insulin, epinephrine, norepinephrine, growth hormone, ACTH and cortisol, most likely reflecting a condition of stress. Normalization of all these hormones occurred with recovery. Plasma aldosterone concentrations were normal. The increased plasma levels of insulin, but also of catecholamines and growth hormone, created a condition promoting potassium uptake in muscle cells. We suggest that stress may play a role in the pathophysiology of the paralytic attacks in this disorder.

Adrenocorticotropic Hormone↗
PubMed1986

Identification of M2 muscarinic receptors in membranes from bovine cerebral basal arteries.

Muscarinic receptors were identified in membrane preparations from bovine cerebral arteries by the specific binding of [3H]-quinuclidinyl benzilate. The total amount of binding sites is relatively high: 1.5 pmol/mg protein, as compared to 0.91 pmol/mg for bovine cerebral cortex and 0.08 pmol/mg for heart muscle. In this study we show that the majority of these sites correspond to M2-receptors: 84% of the sites display low affinity for pirenzepine. In addition, GTP causes a rightward shift and steepening of the carbachol competition binding curve. In the presence of GTP, the alkylating reagent N-ethylmaleimide causes a 28-fold increase of the affinity for carbachol. This phenomenon is also observed on bovine heart membranes where muscarinic receptors are known to be of the M2 type. In contrast, muscarinic receptors in cerebral cortex, predominantly of the M1-type, show only a 4-fold increase in agonist affinity by N-ethylmaleimide. These findings suggest that the ability of N-ethylmaleimide to modulate the agonist affinity is an additional criterion for the characterization of muscarinic M2-type receptors.

Animals↗