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Titolo:
DISTRIBUTION OF [H-3] ZOLPIDEM BINDING-SITES IN RELATION TO MESSENGER-RNA ENCODING THE ALPHA-1, BETA-2 AND GAMMA-2 SUBUNITS OF GABA(A) RECEPTORS IN RAT-BRAIN
Autore:
DUNCAN GE; BREESE GR; CRISWELL HE; MCCOWN TJ; HERBERT JS; DEVAUD LL; MORROW AL;
Indirizzi:
UNIV N CAROLINA,SCH MED,DEPT PSYCHIAT CHAPEL HILL NC 27599 UNIV N CAROLINA,SCH MED,BRAIN & DEV RES CTR CHAPEL HILL NC 27599 UNIV N CAROLINA,SCH MED,CTR ALCOHOL STUDIES CHAPEL HILL NC 27599
Titolo Testata:
Neuroscience
fascicolo: 4, volume: 64, anno: 1995,
pagine: 1113 - 1128
SICI:
0306-4522(1995)64:4<1113:DO[ZBI>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
AMINOBUTYRIC ACID(A) RECEPTORS; CENTRAL-NERVOUS-SYSTEM; A-RECEPTOR; BENZODIAZEPINE RECEPTORS; CHRONIC ETHANOL; FUNCTIONAL EXPRESSION; INFERIOR COLLICULUS; ION CHANNELS; 2 FORMS; SUBTYPES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
70
Recensione:
Indirizzi per estratti:
Citazione:
G.E. Duncan et al., "DISTRIBUTION OF [H-3] ZOLPIDEM BINDING-SITES IN RELATION TO MESSENGER-RNA ENCODING THE ALPHA-1, BETA-2 AND GAMMA-2 SUBUNITS OF GABA(A) RECEPTORS IN RAT-BRAIN", Neuroscience, 64(4), 1995, pp. 1113-1128

Abstract

Localization of the messenger RNAs that encode the alpha 1, beta 2 and gamma 2 subunits of GABA(A) showed a distinct topographic pattern inrat brain which corresponded with [H-3]zolpidem binding in most brainregions. The close topographic correspondence between the specific receptor subunits examined and the distribution of [H-3]zolpidem bindingsires provides support for the hypothesis that this benzodiazepine type 1 selective ligand binds to a GABA(A) receptor that consists of alpha 1, beta 2 and gamma 2 subunits in the rat brain. Brain regions withrelatively high densities of alpha 1, beta 2 and gamma 2 subunits of GABA(A) and [H-3]zolpidem binding included olfactory bulb, medial septum, ventral pallidum, diagonal band, inferior colliculus, substantia nigra pars reticulata and specific layers of the cortex. Two areas withlow [H-3]zolpidem binding and a virtual absence of these GABA(A) receptor subunit messenger RNAs were the lateral septum and the striatum. In contrast to the discrete pattern observed for alpha 1 and beta 2 subunit messenger RNAs, the gamma 2 subunit messenger RNA was distributed more diffusely in brain. Only the hippocampus, layer 2 of the piriform cortex and the cerebellum showed a strong concentration of the gamma 2 subunit messenger RNA. It was determined with a polymerase chain reaction assay that both long and short variants of the gamma 2 subunitmessenger RNAs were present within several of the brain sites selected for examination. Sites with high densities of [H-3]zolpidem binding sites had a greater relative abundance of the gamma 2 long splice variant, compared to the gamma 2 short variant. There were some regions that expressed high levels of alpha 1, beta 2 and gamma 2S subunit messenger RNAs but low [H-3]zolpidem binding, suggesting that gamma 2 splice variant expression may modulate high-affinity [H-3]zolpidem binding. To determine relationships between in vitro [H-3]zolpidem binding andfunctional sensitivity in vivo, interactions between zolpidem and GABA were assessed in brain regions that contained high and low densitiesof [H-3]zolpidem binding sites. In the medial septum, a brain region with a high concentration of [H-3]zolpidem binding sites, iontophoretic application of zolpidem enhanced the inhibitory effect of GABA responses on 70% of the neurons examined. In the lateral septum, which contains very low densities of [H-3]zolpidem binding sites, neurons were not sensitive to zolpidem enhancement of GABA-induced inhibition. Theseelectrophysiological results demonstrate a correspondence between theregional distribution of [H-3]zolpidem binding in vitro and functional sensitivity to the drug in vivo.

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Documento generato il 15/08/20 alle ore 16:51:54