PubMed Health⌕ Search

PubMed · 7748318

Functional alterations in GABAA receptor complex induced by ethanol.

Abstract

Possible direct actions of ethanol on cerebral GABAA receptor complex have been analyzed using purified GABAA receptor complex from the bovine cerebral cortex and its reconstituted vesicles. Addition of ethanol to the reconstituted vesicles with purified GABAA receptor complex induced a significant increase of GABA-dependent 36Cl- influx. Furthermore, the reconstituted GABAA receptor pretreated with 20 mM ethanol, which had no effect on GABAA receptor binding, also showed an increase of the GABA-dependent 36Cl- influx. On the other hand, the GABA-dependent 36Cl- influx into membrane vesicles prepared from alcohol dependent mouse brain showed a significant decrease, although this decrease was found to be recovered at 8 hours after the withdrawal of ethanol inhalation. Moreover, the expression of mRNA for GABAA receptor alpha 1-subunit in the brain showed an elevation in alcohol dependent condition, although this elevation was recovered to the control level after the withdrawal of alcohol inhalation. The present results suggest that continuous inhalation of ethanol in vivo may induce not only the alterations in the function of GABAA receptor complex but also that in the expression of mRNA for the receptor in the brain.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

K Kuriyama, T Ueha, M Hirouchi, T Hashimoto, S Ohkuma. 1993. Functional alterations in GABAA receptor complex induced by ethanol.. https://pubmed.ncbi.nlm.nih.gov/7748318/

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

How does alcohol impair neuronal migration?

Maternal alcohol consumption during pregnancy can cause serious birth defects, of which fetal alcohol syndrome (FAS) is the most devastating. Recognized by characteristic craniofacial abnormalities and growth deficiency, this condition produces severe alcohol-induced damage in the developing brain. FAS children experience ataxia; deficits in intellectual functioning; and difficulties in learning, memory, problem solving, and attention. Multiple aspects of central nervous system development can be affected by alcohol exposure, but the most striking abnormalities are neuronal and glial migration. Little is known about cellular mechanisms by which alcohol affects the migration of immature neurons. Recently, it has been found that Ca(2+) signaling and cyclic nucleotide signaling are the central targets of the action of alcohol in neuronal cell migration. Most importantly, the aberrant migration of immature neurons caused by alcohol exposure is significantly ameliorated by controlling the activity of these second-messenger pathways. In this Mini-Review, we first describe how alcohol exposure impairs the migration of cerebellar granule cells and then discuss the signaling mechanisms involved.

Alcoholism↗

The alcoholic lung: epidemiology, pathophysiology, and potential therapies.

Epidemiological evidence gathered only in the past decade reveals that alcohol abuse independently increases the risk of developing the acute respiratory distress syndrome by as much as three- to fourfold. Experimental models and clinical studies are beginning to elucidate the mechanisms underlying this previously unrecognized association and are revealing for the first time that chronic alcohol abuse causes discrete changes, particularly within the alveolar epithelium, that render the lung susceptible to acute edematous injury in response to sepsis, trauma, and other inflammatory insults. Recent studies in relevant animal models as well as in human subjects are identifying common mechanisms by which alcohol abuse targets both the alveolar epithelium and the alveolar macrophage, such that the risks for acute lung injury and pulmonary infections are inextricably linked. Specifically, chronic alcohol ingestion decreases the levels of the antioxidant glutathione within the alveolar space by as much as 80-90%, and, as a consequence, impairs alveolar epithelial surfactant production and barrier integrity, decreases alveolar macrophage function, and renders the lung susceptible to oxidant-mediated injury. These changes are often subclinical and may not manifest as detectable lung impairment until challenged by an acute insult such as sepsis or trauma. However, even otherwise healthy alcoholics have evidence of severe oxidant stress in the alveolar space that correlates with alveolar epithelial and macrophage dysfunction. This review focuses on the epidemiology and the pathophysiology of alcohol-induced lung dysfunction and discusses potential new treatments suggested by recent experimental findings.

Alcoholism↗