Multiple benzodiazepine receptors: Structures in the brain or structures in the mind? A critical review

Martin, Ian L.; Brown, ChloëL.; Doble, Adam

doi:10.1016/0024-3205(83)90043-7

Cited by 70 publications

(9 citation statements)

References 37 publications

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“…This would seem to suggest that the assignment of pre-and post-synaptic localization of CL binding may not be entirely as clear as was once thought, and certainly raises caution in any interpretation regarding sleep-related function at pre-or post-synaptic sites. Finally, authors such as Martin, Brown and Doble (1983) have called into question the concept of BZ receptor multiplicity. Although there are a great deal of data suggesting multiplicity (Klepner et al, 1979;Gee and Yamamura, 1982;Lo et al, 1983;Young etal., 1981), this caution should also be borne in mind.…”

Section: Discussionmentioning

confidence: 98%

Sleep and benzodiazepine receptor sub-types

Mendelson

Martin

Perlis

et al. 1987

J. Neural Transmission

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CL 218,872, which preferentially binds to benzodiazepine (BZ) type 1 receptors, and flurazepam, which is thought to bind to both types 1 and 2, were given alone and in combination to rats. CL 218,872 had little effect on sleep latency, but significantly increased total sleep time. As expected, flurazepam both shortened sleep latency and prolonged total sleep. Pretreatment with CL 218,872 had no effect on these alterations in sleep induced by flurazepam. The implications for possible significance of sub-typing of BZ receptors are discussed.

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Section: Discussionmentioning

confidence: 98%

Sleep and benzodiazepine receptor sub-types

Mendelson

Martin

Perlis

et al. 1987

J. Neural Transmission

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“…The heterogeneity of binding sites has also been demonstrated autoradiographically (Young et al, 198 I;Niehoff and Whitehouse, 1983), by photoaffinity labeling (Sieghart and Karobath, 1980), by differential solubilization with Triton X-100 (SBbato et al, 198 la;Lo et al, 1983), by regional differences in glycosylation of the BZD receptor protein (Sweetnam and Tallman, 1986) and by lesions of the noradrenergic pathway with 6-hydroxydopamine, 2,4,5-trihydroxyphenylalanine (6-OH-Dopa), or DSP 4 (Skbato et al, 1981b;Medina and Novas, 1983;Lo et al, 1983). However, in spite of this considerable amount of evidence suggesting the existence of multiple BZD receptors, a phenomenon of true negative cooperativity between adjacent receptor sites cannot be ruled out (Lippa et al, 1982;Martin et al, 1983).…”

Section: Discussionmentioning

confidence: 99%

n‐[³H]Butyl‐β‐Carboline‐3‐Carboxylate, a Putative Endogenous Ligand, Binds Preferentially to Subtype 1 of Central Benzodiazepine Receptors

Medina

Stein

Robertis

1989

Journal of Neurochemistry

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Synthetic n-butyl beta-carboline-3-carboxylate, an endogenous central benzodiazepine receptor inhibitor found in brain, was tritium-labeled from the butenyl ester. Binding of this [3H]beta-carboline was concentrated particularly in the synaptosomal membrane fraction of the cerebral cortex; this fraction showed a single type of high-affinity site (KD = 2.7 +/- 0.1 nM) with a Bmax of 1.16 +/- 0.08 pmol/mg of protein. The number of sites labeled was about half of that obtained with [3H]flunitrazepam binding (Bmax = 2.36 +/- 0.06 pmol/mg of protein). On the other hand, in the cerebellum, both ligands bound to practically the same number of sites. When [3H]flunitrazepam binding was done in the presence of 10(-11)-10(-5) M butyl beta-carboline, the differences between the two brain regions were more apparent. In cerebellar membranes the data fitted a straight line in the Eadie-Hofstee plot; this finding and a Hill number near unity suggest a single type of binding site. In the cortical membranes the data of binding fitted a concave curve, and the Hill number was 0.6. These are characteristics of two types of binding sites with different affinities (KD1 = 0.6-1.5 nM and KD2 = 12-18 nM). The differentiation of a high- and low-affinity site in the cerebral cortex was corroborated by experiments in which [3H]butyl beta-carboline binding was displaced by the triazolopyridazine CL 218,872. These results demonstrate that in the cerebral cortex there are two subtypes of sites (1 and 2) of central benzodiazepine receptors and that CL 218,872 binds preferentially to subtype 1.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…Because their use is so ubiquitous, benzodiazepines have been actively investigated in numerous laboratory settings, and their clinical and laboratory effects have been extensively reviewed (Tallman et al, 1980; Martin et al, 1980; Killiam and Suria, 1980; Olsen et al, 1984Olsen et al, , 1986). Much of the earlier research with these compounds focused on their effects on animal and human behavior.…”

Section: Benzodiazepine Receptorsmentioning

confidence: 99%

Mechanisms of Action of Anticonvulsant Drugs

DeLorenzo

1988

Epilepsia

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Understanding the mechanisms of action of anticonvulsant drugs has been a major research effort of neuroscientists for the last three decades. Numerous biochemical and electrophysiological processes have been shown to be modulated by anticonvulsant drugs. However, clear correlations of these effects with anticonvulsant activity are often difficult to determine. Over the last 5 years, several major research areas have developed that shed new light on the mechanisms of action of anticonvulsant drugs. Although a complete discussion of all aspects of anticonvulsant research are not possible in the scope of this article, a description of benzodiazepine receptors, mechanisms involved in neuronal sustaining repetitive firing, and calcium regulation of neuronal function have direct bearing on neuronal excitability and ultimately on anticonvulsant drug effect. Each of these major research areas has opened new insights into our understanding of molecular mechanisms of how anticonvulsant drugs work.

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Multiple benzodiazepine receptors: Structures in the brain or structures in the mind? A critical review

Cited by 70 publications

References 37 publications

Sleep and benzodiazepine receptor sub-types

Sleep and benzodiazepine receptor sub-types

n‐[³H]Butyl‐β‐Carboline‐3‐Carboxylate, a Putative Endogenous Ligand, Binds Preferentially to Subtype 1 of Central Benzodiazepine Receptors

Mechanisms of Action of Anticonvulsant Drugs

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Multiple benzodiazepine receptors: Structures in the brain or structures in the mind? A critical review

Cited by 70 publications

References 37 publications

Sleep and benzodiazepine receptor sub-types

Sleep and benzodiazepine receptor sub-types

n‐[3H]Butyl‐β‐Carboline‐3‐Carboxylate, a Putative Endogenous Ligand, Binds Preferentially to Subtype 1 of Central Benzodiazepine Receptors

Mechanisms of Action of Anticonvulsant Drugs

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n‐[³H]Butyl‐β‐Carboline‐3‐Carboxylate, a Putative Endogenous Ligand, Binds Preferentially to Subtype 1 of Central Benzodiazepine Receptors