Cerebellar GABAa receptor selective for a behavioral alcohol antagonist
Article Abstract:
Many pharmacologic agents exert their effects by binding to cellular receptors; investigation of receptor biochemistry has shown this area to be extremely rich and varied. Benzodiazepines, a widely prescribed class of anticonvulsants and anxiety-reducing drugs, act by binding to the same receptors as the naturally occurring transmitter substance GABA (gamma aminobutyric acid). However, GABA receptors have three different classes of receptor subunits, termed alpha, beta, and gamma, and these subunit classes contain several variants. Each different composition of GABA receptor complex has a different pharmacological profile. The techniques of molecular biology can be used to produce functional receptors in the laboratory according to specification. Using these techniques, investigators have identified a novel form of GABA receptor which may play a role in the coordination of walking. Researchers cloned a gene for a novel subunit, which they termed alpha 6. This specific subunit seems to be expressed only in the granule cells of the cerebellum, a part of the brain responsible for coordination and motor learning. When the alpha 6 subunit was used to construct functioning GABA receptors, these receptors were found to bind the benzodiazepine drug Ro15-4513, but not to other benzodiazepines. Using antibodies to obtain natural GABA receptors from the rat cerebellum, investigators confirmed that similar binding properties occurred in the brain as well. The results demonstrate the existence of a unique form of GABA receptor in the cerebellum. Benzodiazepine Ro15-4513 is capable of reducing the lack of motor coordination and the ataxia resulting from alcohol intoxication, suggesting that the newly identified GABA receptor may play an important role in these processes. (Consumer Summary produced by Reliance Medical Information, Inc.)
Publication Name: Nature
Subject: Zoology and wildlife conservation
ISSN: 0028-0836
Year: 1990
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Benzodiazepine-induced motor impairment linked to point mutation in cerebellar GABA-A receptor
Article Abstract:
Alcohol-non-tolerant (ANT) rats carry a gene that expresses the alpha-six subunit of the granule-cell-specific gamma-aminobutyric acid (GABA-A). A point mutation of this gene identified through polymerase chain reaction causes the ANT rats to be susceptible to abnormal motor function due to diazepam and other benzodiazepine agonists. The potentiation of GABA-A may cause this sensitivity to both benzodiazepine-related compounds and to alcohol.
Publication Name: Nature
Subject: Zoology and wildlife conservation
ISSN: 0028-0836
Year: 1993
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A thorny issue
Article Abstract:
A study is conducted to identify a protein that makes spines grow on nerve cells. It is demonstrated that overproduction of GluR2 causes an increase in both the density and the size of spines in cultured hippocampal neuronsand this effect depends on one portion of the protein, which is exposed to the outside of the cell.
Publication Name: Nature
Subject: Zoology and wildlife conservation
ISSN: 0028-0836
Year: 2003
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