scholarly journals Kinetic parameters of GABA receptor binding by rat adenohypophysis membranes under conditions of modeling various levels of corticosteroids and ACGT in the body

1993 ◽  
Vol 39 (6) ◽  
pp. 43-46
Author(s):  
T. M. Mishunina ◽  
V. Ya. Kononenko
Keyword(s):  
Kinetic Parameters ◽  
Gaba Receptors ◽  
Gaba Receptor ◽  
Plasma Membranes ◽  
Specific Binding ◽  
The Body ◽  
Noticeable Increase ◽  
High Affinity ◽  
Gaba Binding ◽  
Hormonal Levels

Kinetic parameters of l4C-GABA specific binding by rat adenohypophyseal plasma membranes were studied in experiments on modelling various corticosteroid and ACTH levels in animal body. A single hydrocortisone injection did not change Ka for high- and low-affinity GABA receptors, the number of the former (Bmax) increasing in this case. Repeated hydrocortisone injections were associated with Ko reduction for high-affinity GABA receptors and a noticeable increase of Kn for low-affinity receptors, with their number reducing. ACTH injection did not change the kinetic parameters of GABA binding with receptors. The number of high-affinity GABA receptors and their affinity reduced after removal of adrenals whereas the number of low-affinity receptors in this case was increasing. A single hydrocortisone injection to adrenalectomized rats had a normalizing effect on adenohypophyseal GABA receptors. Analysis of the results and changes in blood hormonal levels indicated that affinity changes in high-affinity receptors and changed number of low-affinity adenohypophyseal GABA receptors correlated with changes in ACTH and hydrocortisone changes.

GABAA receptor binding and localization in the tiger salamander retina

2000 ◽  
Vol 17 (1) ◽  
pp. 11-21 ◽  
Author(s):  
HAO WANG ◽  
KELLY M. STANDIFER ◽  
DAVID M. SHERRY
Keyword(s):  
Gaba Receptors ◽  
Radioligand Binding ◽  
Specific Binding ◽  
Horizontal Cell ◽  
Tiger Salamander ◽  
Gamma Aminobutyric Acid ◽  
Binding Studies ◽  
Binding Properties ◽  
Gaba Binding ◽  
Sr 95531

Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the retina and also appears to act as a trophic factor regulating photoreceptor development and regeneration. Although the tiger salamander is a major model system for the study of retinal circuitry and regeneration, our understanding of GABA receptors in this species is almost exclusively based on the results of physiological studies. Therefore, we have examined the pharmacological binding properties of GABAA receptors and their anatomical localization in the tiger salamander retina. Radioligand-binding studies showed that specific 3H-GABA binding to GABAA receptors was dominated by a single high-affinity binding site (Kd = 15.6 ± 6.9 nM). Specific binding of 3H-GABA was almost completely eliminated by muscimol (Ki = 105 ± 62 nM) and bicuculline (Ki = 14.3 ± 2.2 μM); however, SR-95531 only displaced about 40% of specific 3H-GABA binding (Ki = 35.0 ± 3.8 nM). These data indicate that there are at least two subtypes of GABAA receptors present in the salamander retina that can be distinguished by their antagonist binding properties: one sensitive to both bicuculline and SR-95531, and one sensitive to bicuculline but insensitive to SR-95531. Because localization of GABA receptors in the salamander retina by immunocytochemistry is problematic, GABAA receptors were localized by fluorescent ligand binding combined with immunocytochemical labeling for cell specific markers. Binding of fluorescently labeled muscimol to GABAA receptors was present in both plexiform layers and on photoreceptor cell bodies. GABAA receptors in the outer plexiform layer were localized to both photoreceptor terminals and horizontal cell processes.

Molecular Mechanisms Mediating the Action of Diazepam on GABA Receptors

1978 ◽  
Vol 133 (3) ◽  
pp. 239-248 ◽  
Author(s):  
E. Costa ◽  
A. Guidotti ◽  
G. Toffano
Keyword(s):  
Gaba Receptors ◽  
Molecular Mechanisms ◽  
Type A ◽  
Anxiolytic Activity ◽  
The Other ◽  
Synaptic Membranes ◽  
Kinetic Properties ◽  
Endogenous Inhibitor ◽  
High Affinity ◽  
Gaba Binding

SummaryTwo types of crude synaptic membranes have been prepared which differ in their kinetic properties to bind 3H-GABA in a Na+-free medium. One type (B) has one type of receptor (affinity or KD about 0.2 μM), the other type (A) has two populations of receptors which have a high (0.16 μM) and a low (.02 μM) KD for GABA binding. This difference is due to the presence of a selective endogenous inhibitor of the high affinity receptor for GABA, a thermostable protein of about 15,000 molecular weight. Inhibitor action is counteracted by diazepam (7 x 10-7M), competitively. Clonazepam is more active but chlordiazepoxide is less active than diazepam. Two enantiomers of a benzodiazepine were studied. One of them is endowed with anxiolytic activity and nullifies the action of the endogenous inhibitor on high affinity GABA binding, the other is devoid of anxiolytic activity and is inactive against the inhibitor. The endogenous protein inhibitor also competitively blocks the high affinity binding of 3H-diazepam to Type A membranes. It is concluded that the endogenous inhibitor and diazepam act on the same receptor; and suggested that the endogenous inhibitor may be the natural ligand for the brain receptors that bind benzodiazepines with high affinity.

scholarly journals Contribution of gangliosides to thyroxin binding with plasma membranes

1995 ◽  
Vol 41 (2) ◽  
pp. 28-30
Author(s):  
T. S. Saatov ◽  
F. Ya. Gulyamova ◽  
G. U. Usmanova
Keyword(s):  
Binding Sites ◽  
Plasma Membranes ◽  
Binding Capacity ◽  
Specific Binding ◽  
Brain Cell ◽  
Cell Recognition ◽  
High Affinity ◽  
Specific Binding Sites

Besides intracellular receptors of thyroid hormones, specific binding sites for T3 and T4 were detected on plasma membranes (PM) of some cells and a relationship between membrane reception .and lipid composition of membranes shown. The parameters of 125I-T4 binding to highly purified PM of hepatic and cerebral cells of rats were studied. The hepatic and cerebral cellular membranes were found to contain two sites of hormone binding each, one of these sites being characterized by a high affinity and low capacity, and the other by low affinity and a higher binding capacity. The association constant of highly affine site of hepatocyte membranes was found to be higher than that of brain cell membranes. T4 membranous receptors may be significant in the process of cell “recognition" by the hormone. In vivo and in vitro experiments with 125I-T4 and 14C-labeled thyroxin in ganglioside fractions showed appreciable binding of the hormone to Gm3 fraction, this evidently pointing to participation of this, ganglioside in T4 interaction with membrane receptor. It is possible that gangliosides situated on membranous surface are components of or function as receptors.

Regulation of (Ca2+-Mg2+)-ATPase activity by calcitonin binding to rat liver plasma membranes

1985 ◽  
Vol 110 (1) ◽  
pp. 124-129 ◽  
Author(s):  
Masayoshi Yamaguchi ◽  
Michiyo Ito
Keyword(s):  
Plasma Membrane ◽  
Atpase Activity ◽  
Rat Liver ◽  
Plasma Membranes ◽  
Specific Binding ◽  
Inhibitory Effect ◽  
Maximal Inhibition ◽  
Low Concentration ◽  
High Affinity ◽  
Rat Liver Plasma Membranes

Abstract. The plasma membranes isolated from rat liver bound 125I-labelled ([125I]) synthetic [Asu1,7]eel calcitonin (CT), with increasing concentrations of [125I]CT. This specific binding was completely saturated at a concentration of 0.5 nm CT. A high affinity Ca2+ -stimulated, Mg2+-dependent ATPase [(Ca2+-Mg2+)-ATPase] activity in the plasma membranes was significantly decreased by the presence of a very low concentration of CT (7.4 pm), although the hormone did not affect the activity of the plasma membrane 5′-nucleotidase. The concentration of CT needed for maximal inhibition of (Ca2+-Mg2+)-ATPase in the plasma membranes was less than 0.74 nm. The plasma membranes washed with 10−3% digitonin did not show an inhibitory effect of CT on (Ca2+-Mg2+)-ATPase activity, while the reagent did not have a significant effect on the enzyme. These results suggest that the inhibition of (Ca2+-Mg2+)-ATPase activity maybe part of the mechanism by which CT elevates cytosolic Ca2+ in liver cells.

Conformation as the Therapeutic Target for Neurodegenerative Diseases

2017 ◽  
Vol 14 (4) ◽  
pp. 393-402 ◽  
Author(s):  
Rajaraman Krishnan ◽  
Franz Hefti ◽  
Haim Tsubery ◽  
Michal Lulu ◽  
Ming Proschitsky ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Neurodegenerative Diseases ◽  
Protein Misfolding ◽  
Specific Binding ◽  
Drug Candidate ◽  
High Affinity ◽  
Novel Approach ◽  
Multiple Protein ◽  
Clinical Benefits ◽  
Effective Drugs

Therapeutic strategies that target pathways of protein misfolding and the toxicity of intermediates along these pathways are mainly at discovery and early development stages, with the exception of monoclonal antibodies that have mainly failed to produce convincing clinical benefits in late stage trials. The clinical failures represent potentially critical lessons for future neurodegenerative disease drug development. More effective drugs may be achieved by pursuing the following two strategies. First, conformational targeting of aggregates of misfolded proteins, rather than less specific binding that includes monomer subunits, which vastly outnumber the toxic targets. Second, since neurodegenerative diseases frequently include more than one potential protein pathology, generic targeting of aggregates by shape might also be a crucial feature of a drug candidate. Incorporating both of these critical features into a viable drug candidate along with high affinity binding has not been achieved with small molecule approaches or with antibody fragments. Monoclonal antibodies developed so far are not broadly acting through conformational recognition. Using GAIM (General Amyloid Interaction Motif) represents a novel approach that incorporates high affinity conformational recognition for multiple protein assemblies, as well as recognition of an array of assemblies along the misfolding pathway between oligomers and fibers. A GAIM-Ig fusion, NPT088, is nearing clinical testing.

scholarly journals Heterogeneous expression of GABA receptor‐like subunits LCCH3 and GRD reveals functional diversity of GABA receptors in the honeybee Apis mellifera

2020 ◽  
Vol 177 (17) ◽  
pp. 3924-3940
Author(s):  
Christopher Henry ◽  
Thierry Cens ◽  
Pierre Charnet ◽  
Catherine Cohen‐Solal ◽  
Claude Collet ◽  
...  
Keyword(s):  
Apis Mellifera ◽  
Functional Diversity ◽  
Gaba Receptors ◽  
Gaba Receptor ◽  
Heterogeneous Expression

Asymmetric Dopaminergic Dysfunction in Brain-First versus Body-First Parkinson’s Disease Subtypes

2021 ◽  
pp. 1-11
Author(s):  
Karoline Knudsen ◽  
Tatyana D. Fedorova ◽  
Jacob Horsager ◽  
Katrine B. Andersen ◽  
Casper Skjærbæk ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
De Novo ◽  
Specific Binding ◽  
Asymmetry Index ◽  
The Body ◽  
Specific Binding Ratio ◽  
Dat Spect ◽  
Vagal Innervation ◽  
Nigrostriatal Degeneration

Background: We have hypothesized that Parkinson’s disease (PD) comprises two subtypes. Brain-first, where pathogenic α-synuclein initially forms unilaterally in one hemisphere leading to asymmetric nigrostriatal degeneration, and body-first with initial enteric pathology, which spreads through overlapping vagal innervation leading to more symmetric brainstem involvement and hence more symmetric nigrostriatal degeneration. Isolated REM sleep behaviour disorder has been identified as a strong marker of the body-first type. Objective: To analyse striatal asymmetry in [18F]FDOPA PET and [123I]FP-CIT DaT SPECT data from iRBD patients, de novo PD patients with RBD (PD +RBD) and de novo PD patients without RBD (PD - RBD). These groups were defined as prodromal body-first, de novo body-first, and de novo brain-first, respectively. Methods: We included [18F]FDOPA PET scans from 21 iRBD patients, 11 de novo PD +RBD, 22 de novo PD - RBD, and 18 controls subjects. Also, [123I]FP-CIT DaT SPECT data from iRBD and de novo PD patients with unknown RBD status from the PPPMI dataset was analysed. Lowest putamen specific binding ratio and putamen asymmetry index (AI) was defined. Results: Nigrostriatal degeneration was significantly more symmetric in patients with RBD versus patients without RBD or with unknown RBD status in both FDOPA (p = 0.001) and DaT SPECT (p = 0.001) datasets. Conclusion: iRBD subjects and de novo PD +RBD patients present with significantly more symmetric nigrostriatal dopaminergic degeneration compared to de novo PD - RBD patients. The results support the hypothesis that body-first PD is characterized by more symmetric distribution most likely due to more symmetric propagation of pathogenic α-synuclein compared to brain-first PD.

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