Solubilization and properties of a benzodiazepine receptor from calf cortex

Sherman-Gold, Rivka; Dudai, Yadin

doi:10.1016/0006-8993(80)90765-9

Cited by 43 publications

(18 citation statements)

References 14 publications

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“…Behaviour of solubilized receptors on sucrose density gradients suggests either a heterogeneous nature of these structures or formation of aggregates. Similar results were obtained by several authors who analysed some other plasma membrane receptors (Sobel et al, 1977;Guellaen et al, 1979;Sherman-Gold & Dudai, 1980). Our results show that CHAPS represents a very suitable agent for solubilization of dopaminereceptors from the bovine caudate nucleus, yield of D2-receptors is relatively high and these receptors remain in their native form.…”

Section: Discussionsupporting

confidence: 91%

Solubilization of dopamine‐D₂receptors from synaptosomal membranes of the bovine caudate nucleus

Kidrič

Petrović²,

Šoškić

et al. 1984

British J Pharmacology

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Section: Discussionsupporting

confidence: 91%

Solubilization of dopamine‐D₂receptors from synaptosomal membranes of the bovine caudate nucleus

Kidrič

Petrović²,

Šoškić

et al. 1984

British J Pharmacology

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“…The protection against the inactivation of solubilized receptors by TNM, provided by GABA and a combination of GABA and a benzodiazepine, also corroborates previous reports that the DOC-solubllized benzodiazepine receptor bears a GABA recognition site [3,8]. However, the relationship between the benzodiazepine and the GABA sites (e.g., do they reside in close proximity or on separate polypeptides) as well as direct evidence for the identity and the location of the tyrosyl residue(s) involved in ligand binding to the receptor, must await the purification of the receptor molecule.…”

Section: Methodssupporting

confidence: 89%

“…We have tested the ability of benzodiazepines and of GABA, which has been reported to interact with the benzodiazepine receptor [3,6], to protect against the TNM effect (table 1) TNM may also modify cysteine or, though less likely, tryptophan residues [7]. Nitration of tyrosine is expected to proceed much slower at pH 6.5 than at pH 8.0, whereas nitration of cysteine is efficient at the lower pH [4,7].…”

Section: Methodsmentioning

confidence: 99%

Involvement of tyrosyl residues in the binding of benzodiazepines to their brain receptors

Sherman-Gold

Dudai

1981

FEBS Letters

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“…Thus, we have demonstrated that a major portion of the putative y-aminobutyrate and benzodiazepine receptor binding proteins in solution have similar physical properties, and y-aminobutyric acid can still enhance the binding of [3H]flunitrazepam both in detergent-solubilized membrane extracts and following various fractionation procedures, a result which agrees with several published reports [13,14,18]. We also found that barbiturate enhancement of [3H]flunitrazepam binding in membranes [lo] was retained in detergent-…”

Section: Sucrose Density Gradient Sedimentationsupporting

confidence: 91%

“…At present there is no evidence to support or discard this possibility. It is also possible that y-aminobutyrate enhancement of benzodiazepine binding, which requires micromolar concentrations of y-aminobutyric acid in membranes [6,9] and in solution [14,18] (and this study), involves a y-aminobutyric binding site other than that detected by direct y-amin~[~H]butyric acid binding, which A reasonable alternative interpretation is that the y-aminobutyrate and benzodiazepine receptors could be one and the same protein. This would not explain the differential solubilization of the benzodiazepine receptor in Triton X-100.…”

Section: Gel Filtrationmentioning

confidence: 90%

Physicochemical Characterization of Detergent‐Solubilized γ‐Aminobutyric Acid and Benzodiazepine Receptor Proteins from Bovine Brain

Stephenson¹,

Watkins²,

Olsen³

1982

European Journal of Biochemistry

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[3H]Muscimol and [3H]flunitrazepam binding activities have been solubilized from bovine cortex using the ionic detergent sodium deoxycholate. The soluble receptor proteins were shown to bind [3H]muscimol with a dissociation constant, Kd, of 12 nM and a binding capacity (B,,, The two binding activities were also found to comigrate after sedimentation in a sucrose density gradient. The hydrodynamic properties of the assumed protein-detergent complexes were determined by gel filtration and sedimentation through gradients of sucrose in H2O or 'HzO. Under the conditions employed, the parameters for both the putative y-aminobutyric acid and benzodiazepine receptors were : partial specific volume, 0.73 ml 8 -l ; sedimentation coefficient, 12.5 S; molecular weight, 355000; and frictional ratio 1.46. These observations are consistent with the conclusion that the majority of both binding activities solubilized in deoxycholate reside in a single macromolecular complex. However, Triton X-100 selectively solubilized the benzodiazepine binding activity. This suggests that the two binding activities can be at least partially separated.y-Aminobutyric acid is the major inhibitory neurotransmitter in mammalian brain and it is thought to mediate its transmission effects through a postsynaptic membrane protein, the y-aminobutyrate receptor [I ,2]. Several groups have demonstrated the presence of high-affinity, saturable, specific binding of y-amin~[~H]butyric acid and its pharmacologically active analogues such as muscirnol to brain synaptic membranes [3 -51 and these binding sites are recognized as the y-aminobutyrate receptor protein(s). Recent evidence has shown that y-aminobutyric acid and structurally related compounds can enhance the specific binding in brain of the benzodiazepine ligands [6], a class of compounds that possess anxiolytic, anticonvulsant, sedative-hypnotic, muscle relaxant and central nervous system depressant properties [7,8]. Benzodiazepines can protect y-aminobutyrate binding activity against heat inactivation and denaturation by protein reagents [9]. Thus, it has been suggested that the y-aminobutyrate receptor may be a complex multi-subunit protein that mediates central nervous system mechanisms which can be modulated via allosteric interactions of the benzodiazepines ; another class of compounds, the barbiturates, also modulate this receptor complex [lo].Proteins binding both y-aminobutyric acid [ll -151 and benzodiazepines [14 -181 have been solubilized by mild detergents. They were shown to possess dissimilar apparent sizes under some conditions ; thus the major protein with y-aminobutyrate-binding activity in deoxycholate solution showed an apparent molecular weight of 900 000 compared to globular standard proteins [I I] while the protein with benzodiazepinebinding activity in Lubrol or Triton X-100 solution reportedly had a smaller apparent M , of approximately 200000 [16,17]. More recent reports that appeared during the preparation of this manuscript suggest that the two binding proteins show simi...

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Solubilization and properties of a benzodiazepine receptor from calf cortex

Cited by 43 publications

References 14 publications

Solubilization of dopamine‐D₂receptors from synaptosomal membranes of the bovine caudate nucleus

Solubilization of dopamine‐D₂receptors from synaptosomal membranes of the bovine caudate nucleus

Involvement of tyrosyl residues in the binding of benzodiazepines to their brain receptors

Physicochemical Characterization of Detergent‐Solubilized γ‐Aminobutyric Acid and Benzodiazepine Receptor Proteins from Bovine Brain

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Solubilization and properties of a benzodiazepine receptor from calf cortex

Cited by 43 publications

References 14 publications

Solubilization of dopamine‐D2receptors from synaptosomal membranes of the bovine caudate nucleus

Solubilization of dopamine‐D2receptors from synaptosomal membranes of the bovine caudate nucleus

Involvement of tyrosyl residues in the binding of benzodiazepines to their brain receptors

Physicochemical Characterization of Detergent‐Solubilized γ‐Aminobutyric Acid and Benzodiazepine Receptor Proteins from Bovine Brain

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Solubilization of dopamine‐D₂receptors from synaptosomal membranes of the bovine caudate nucleus

Solubilization of dopamine‐D₂receptors from synaptosomal membranes of the bovine caudate nucleus