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GABA Receptor Interactions
Published by Hoozhooz on 2007/9/30 (1706 reads)
1: Pharmacol Rev. 2003 Sep;55(3):509-50. Epub 2003 Jul 17.


Molecular mechanisms and therapeutical implications of intramembrane receptor/receptor interactions among heptahelical receptors with examples from the striatopallidal GABA neurons.

Agnati LF, Ferré S, Lluis C, Franco R, Fuxe K.

Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden. Kjell.Fuxe@neuro.ki.se

The molecular basis for the known intramembrane receptor/receptor interactions among G protein-coupled receptors was postulated to be heteromerization based on receptor subtype-specific interactions between different types of receptor homomers. The discovery of GABAB heterodimers started this field rapidly followed by the discovery of heteromerization among isoreceptors of several G protein-coupled receptors such as delta/kappa opioid receptors. Heteromerization was also discovered among distinct types of G protein-coupled receptors with the initial demonstration of somatostatin SSTR5/dopamine D2 and adenosine A1/dopamine D1 heteromeric receptor complexes. The functional meaning of these heteromeric complexes is to achieve direct or indirect (via adapter proteins) intramembrane receptor/receptor interactions in the complex. G protein-coupled receptors also form heteromeric complexes involving direct interactions with ion channel receptors, the best example being the GABAA/dopamine D5 receptor heteromerization, as well as with receptor tyrosine kinases and with receptor activity modulating proteins. As an example, adenosine, dopamine, and glutamate metabotropic receptor/receptor interactions in the striatopallidal GABA neurons are discussed as well as their relevance for Parkinson's disease, schizophrenia, and drug dependence. The heterodimer is only one type of heteromeric complex, and the evidence is equally compatible with the existence of higher order heteromeric complexes, where also adapter proteins such as homer proteins and scaffolding proteins can exist. These complexes may assist in the process of linking G protein-coupled receptors and ion channel receptors together in a receptor mosaic that may have special integrative value and may constitute the molecular basis for some forms of learning and memory.

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

PMID: 12869660 [PubMed - indexed for MEDLINE]

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2: Annu Rev Pharmacol Toxicol. 1982;22:245-77.


Drug interactions at the GABA receptor-ionophore complex.

Olsen RW.

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

PMID: 6282187 [PubMed - indexed for MEDLINE]

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3: Mol Cell Biochem. 1981 Aug 11;38 Spec No(Pt 1):129-46.


GABA agonists. Development and interactions with the GABA receptor complex.

Krogsgaard-Larsen P, Falch E.

This review describes the development of GABA receptor agonists with no detectable affinity for other recognition sites in GABA-mediated synapses. The key compounds are THIP, isoguvacine, and piperidine-4-sulphonic acid (P4S), developed via extensive structural modifications of the potent but not strictly specific GABA agonist muscimol. The structural parameters, which have to be considered in the design of GABA agonists are discussed on the basis of the structures and biological activities of these GABA agonists and a number of related compounds. A model, which summarizes our present knowledge of the structure of the postsynaptic GABA receptors complex, is presented, and the interaction of GABA agonists with various sites in this complex is discussed. Of particular interest are the effects of GABA agonists on the binding of diazepam to the benzodiazepine binding site, assumed to be a structural unit of the GABA receptor complex. While rigid molecules like THIP are capable of activating the GABA receptors, a certain degree of conformational mobility of GABA agonists apparently is a prerequisite for stimulation of diazepam binding in vitro at 0 degree C. The findings suggest that GABA receptor functions involve conformational changes of certain elements, including the attempts to develop GABA agonists with desirable pharmacokinetic and toxicological characteristics. While muscimol is a toxic compound, THIP is well tolerated by animals, and in contrast to isoguvacine, THIP penetrates into the brain after systemic administration to animals, a difference which can be explained on the basis of their protolytic properties. The attempts to develop pro-drugs of isoguvacine capable of penetrating the blood-brain barrier with subsequent decomposition in the brain tissue to isoguvacine are described.

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

PMID: 6270544 [PubMed - indexed for MEDLINE]

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4: J Neurochem. 1981 Jul;37(1):1-13.


GABA-benzodiazepine-barbiturate receptor interactions.

Olsen RW.

Publication Types:
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 6265597 [PubMed - indexed for MEDLINE]
 

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