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Titolo:
MOLECULAR-BASIS FOR REGIONALLY SPECIFIC ACTION OF ETHANOL ON GAMMA-AMINOBUTYRIC ACID(A) RECEPTORS - GENERALIZATION TO OTHER LIGAND-GATED ION CHANNELS
Autore:
CRISWELL HE; SIMSON PE; DUNCAN GE; MCCOWN TJ; HERBERT JS; MORROW AL; BREESE GR;
Indirizzi:
UNIV N CAROLINA,SCH MED,BRAIN & DEV RES CTR,CB 7250 CHAPEL HILL NC 27599 UNIV N CAROLINA,SCH MED,CTR ALCOHOL STUDIES CHAPEL HILL NC 27514 UNIV N CAROLINA,SCH MED,DEPT PSYCHIAT CHAPEL HILL NC 27514
Titolo Testata:
The Journal of pharmacology and experimental therapeutics
fascicolo: 1, volume: 267, anno: 1993,
pagine: 522 - 537
SICI:
0022-3565(1993)267:1<522:MFRSAO>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
GABA-A RECEPTOR; SUBUNIT MESSENGER-RNAS; OPERATED CHLORIDE CHANNELS; CENTRAL-NERVOUS-SYSTEM; SPINAL-CORD NEURONS; RAT-BRAIN; FUNCTIONAL-CHARACTERIZATION; BENZODIAZEPINE RECEPTORS; HIPPOCAMPAL-NEURONS; AUDIOGENIC-SEIZURES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
97
Recensione:
Indirizzi per estratti:
Citazione:
H.E. Criswell et al., "MOLECULAR-BASIS FOR REGIONALLY SPECIFIC ACTION OF ETHANOL ON GAMMA-AMINOBUTYRIC ACID(A) RECEPTORS - GENERALIZATION TO OTHER LIGAND-GATED ION CHANNELS", The Journal of pharmacology and experimental therapeutics, 267(1), 1993, pp. 522-537

Abstract

The present investigation provides evidence that there is neuroanatomical specificity for ethanol enhancement of gamma-aminobutyric acid (GABA)-induced inhibition in mammalian brain and that the expression of a specific GABA(A) isoreceptor is associated with this regional actionof ethanol. Ethanol enhanced responses to iontophoretically applied GABA in the medial septum, inferior colliculus, substantia nigra reticulata, ventral pallidum and the diagonal band of Broca. In contrast to these results, responses to GABA applied to cells in the lateral septum, ventral tegmental area and the hippocampus were not affected by ethanol. In those brain regions where ethanol enhanced responses to GABA,a high concentration of zolpidem binding was found, whereas zolpidem binding was much lower or absent in brain regions where ethanol did not enhance GABA. These observations support the hypothesis that ethanolenhances GABA within specific regions of brain by affecting a GABA(A)receptor with specific structural components. From data obtained within situ hybridization, there was a strong relationship between the regional distribution of zolpidem binding and the expression of specificmRNAs for the alpha-1, beta-2 and gamma-2 GABA(A) receptor subunits at sites where ethanol enhanced responses to GABA. The mRNA for the long and short variants of the gamma-2 subunit were found in brain regions both sensitive and insensitive to the action of ethanol on GABA-induced inhibition. These data were not able to address whether the gamma-2 long variant in combination with the alpha-1 and beta-2 subunits is essential for ethanol enhancement of responses to GABA. However, the observation that the long version of the gamma-2 subunit is present in brain areas where ethanol did not affect GABA function suggests that the presence of the long variant of the gamma-2 subunit alone is not sufficient for ethanol's action to enhance responses to GABA. Rather it is concluded that the appropriate combination of GABA(A) receptor subunits is critical for this action of ethanol. Because the GABA(A) receptor belongs to a superfamily of ligand-gated ion channels, the action of ethanol was examined on responses to agonists acting on receptors linked to other ion channels. As noted for GABA, local application of ethanol altered responses to NMDA, nicotine and glycine when applied tosome, but not all, neurons. It is hypothesized that the action of ethanol to affect some, but not all, responses of agonists for the superfamily of ligand-gated ion channel receptor is based upon specific structural components of these receptors, just as evidence suggests is thecase for GABA(A) isoreceptors.

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Documento generato il 22/09/20 alle ore 04:16:29