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GABA Receptor Structure
Published by Anonymous on 2007/9/30 (1706 reads)
1: J Clin Psychiatry. 2005;66 Suppl 2:14-20.


The GABA-benzodiazepine receptor complex: structure, function, and role in anxiety.

Roy-Byrne PP.

Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA 98104, USA. roybyrne@u.washington.edu

Benzodiazepines bind to a specific site on the gamma-aminobutyric acid (GABA)-benzodiazepine receptor complex. This complex has been implicated in the pathophysiology of anxiety by numerous pre-clinical and clinical studies. Preclinical studies have shown that there are multiple molecular forms of this receptor complex, that these genetically coded variations are linked to specific actions of the benzodiazepines, and that receptors are located in neuroanatomical areas known to mediate the anxiety response in animals and humans. Human studies have shown that patients with pathologic anxiety have anomalous responses to drugs that specifically bind to these receptors and have reduced numbers of benzodiazepine receptors in key brain areas that regulate anxiety responses. More recent preclinical studies suggest that molecular alterations in this receptor complex may produce findings in animals similar to those observed in anxious humans. Finally, chronic treatment with benzodiazepines causes the development of tolerance, which may be associated with molecular changes and a pharmacologic response profile similar to that observed in pathologically anxious humans.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 15762815 [PubMed - indexed for MEDLINE]

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2: Curr Top Med Chem. 2002 Aug;2(8):853-67.


GABA(A)-receptor ligands of flavonoid structure.

Marder M, Paladini AC.

Instituto de Quimica y Fisicoquimica Biologicas, Facultad de Farmacia y Bioquimica, Junin 956, Buenos Aires, 1113, Argentina.

This review describes the new research developments that have established the CNS-activity of some natural flavonoids. The properties of flavone, chrysin, apigenin and cirsiliol are described and a survey of the occurrence of ligands for the benzodiazepine binding site in the flavonoid field is attempted. Natural compounds, structurally related to flavonoids and with similar CNS-activities, are also included. A medicinal chemistry approach to improve the biochemical and pharmacological properties of the flavone nucleus is described alongside with the enumeration of the principal achievements obtained to date. Quantitative structure-activity relationships studies leading to the formulation of pharmacophore models presumably describing the characteristics of the flavone-binding site in the GABA(A)-receptor are summarized.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 12171576 [PubMed - indexed for MEDLINE]

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3: Trends Biochem Sci. 2002 Jun;27(6):280-7.


Erratum in:
Trends Biochem Sci 2002 Jul;27(7):380.

Anxiety over GABA(A) receptor structure relieved by AChBP.

Cromer BA, Morton CJ, Parker MW.

Biota Structural Biology Laboratory, St. Vincent's Institute of Medical Research, 9 Princes Street, Fitzroy, Victoria 3065, Australia. b.cromer@medicine.unimelb.edu.au

The GABA(A) receptor is the primary mediator of inhibitory neurotransmission in the brain and is a major target for neuromodulatory drugs such as benzodiazepines, barbiturates, ethanol and anaesthetics. However, our understanding of the molecular details of this receptor has been limited by a lack of high-resolution structural information. This article presents a new model for the extracellular, ligand-binding domain of the GABA(A) receptor, that is based on the recently determined structure of a soluble acetylcholine-binding protein. The model puts existing mutational and biochemical data into a three-dimensional context, shows details of the GABA- and benzodiazepine-binding sites, and highlights the importance of other regions in allosteric conformational change. This provides a new perspective on existing data and an exciting new framework for understanding this important family of receptors.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 12069787 [PubMed - indexed for MEDLINE]

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4: Tanpakushitsu Kakusan Koso. 1990 Jun;35(8):1455-64.


[Structure and function of GABA receptor in the brain]

[Article in Japanese]

Kuriyama K, Hirouchi M.

Department of Pharmacology, Kyoto Prefectural University of Medicine, Japan.

Publication Types:
Review

PMID: 1695758 [PubMed - indexed for MEDLINE]

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5: Prog Clin Biol Res. 1990;361:231-55.


Molecular biological insights into GABA and benzodiazepine receptor structure.

Tallman JF, Hutchison A.

Ribicoff Research Center, Yale University School of Medicine, New Haven, CT.

Publication Types:
Review

PMID: 1963220 [PubMed - indexed for MEDLINE]

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6: Nippon Yakurigaku Zasshi. 1989 Jul;94(1):7-15.


[Structure and function of gamma-aminobutyric acid (GABA) receptor: current state and prospectives]

[Article in Japanese]

Kuriyama K, Hirouchi M.

Department of Pharmacology, Kyoto Prefectural University of Medicine, Japan.

The gamma-aminobutyric acid (GABA) receptor has been classified into two receptor subtypes (GABAA and GABAB receptors) based on their pharmacological properties. The GABAA receptor in the central nervous system (CNS) has been found to be coupled structurally as well as functionally with the benzodiazepine receptor and Cl- channel. Purified GABAA receptor from bovine brain consisted of both alpha and beta subunits. The complementary DNAs encoding the GABAA receptor alpha and beta subunits have been cloned; and from their elucidated nucleotide sequences, the amino acid sequences of the subunits were deduced. The structure of both subunits, having four putative membrane domains, has been found to be similar to other ligand-gated receptors such as the nicotinic acetylcholine receptor alpha subunit and glycine receptor 48K subunit. Therefore, it has been suggested that these ligand-gated receptors comprise a superfamily. In addition, the presence of similarities in the nucleotide and deduced amino acid sequences of human brain GABAA receptor with those of bovine brain has been noted. On the other hand, the GABAB receptor, which is insensitive to bicuculline but sensitive to baclofen, has been found to be pharmacologically distinct from the GABAA receptor. The GABAB receptor in the brain has been found to be coupled with GTP-binding protein and generates the inhibitory transmission coupled with various intracellular effector systems such as adenylate cyclase and phosphoinositides turnover. The exact structure and function of the GABAB receptor in the CNS, however, remain to be clarified in future studies.

Publication Types:
English Abstract
Review

PMID: 2551802 [PubMed - indexed for MEDLINE]

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7: Adv Exp Med Biol. 1984;175:235-54.


Structure and properties of the brain GABA/benzodiazepine receptor complex.

Barnard EA, Stephenson FA, Sigel E, Mamalaki C, Bilbe G, Constanti A, Smart TG, Brown DA.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 6093456 [PubMed - indexed for MEDLINE]

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8: Adv Exp Med Biol. 1979;123:303-21.


GABA receptor agonists: relationship between structure and biological activity in vivo and in vitro.

Krogsgaard-Larsen P, Krogsgaard-Larsen P, Arnt J, Arnt J.

Publication Types:
Review

PMID: 390994 [PubMed - indexed for MEDLINE]
 

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