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Scientists identify molecular step that causes intoxication

Scientists at UCSF's Ernest Gallo Clinic and Research Center have identified a single brain protein that can account for most of the intoxicating effects of alcohol. The finding pinpoints perhaps the best target yet for a drug to block alcohol's effect and potentially treat alcoholism, the scientists say.

The mechanisms by which alcohol acts on the brain are thought to be similar throughout the animal kingdom, since species from worms and fruit flies to mice and humans all become intoxicated at similar alcohol concentrations. But although studies have identified a number of genes that can partially influence how alcohol affects behavior, this is the first finding that a single gene and the brain protein it codes for - known as an ion channel - are responsible for the intoxicating effects of alcohol in a living organism, according to the researchers.

The discovery was made in a six-year research effort focusing on Caenorhabditis elegans, the roundworm widely studied because about half of its approximately 20,000 genes have counterparts in the human genome.

"We have found that alcohol acts on this channel in nerve cells to cause neural depression and intoxication," said Steven McIntire, MD, PhD. "We would expect that the same process functions in humans, who also have this type of channel." McIntire is senior author of a report on the discovery in the December 12 issue of the journal CELL. He is assistant professor of neurology at UCSF and principal investigator at the UCSF-affiliated Gallo Clinic and Research Center.

Researchers already knew that the gene known as slo-1 codes for a channel-like protein in the brain that can allow potassium ions to pour out of neurons, a normal process that temporarily slows down the neuron's activity. In the study, the scientists discovered that alcohol makes the channel open more frequently, depressing neuron activity and leading to sluggish, uncoordinated movement typical of intoxicat
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Contact: Wallace Ravven
wravven@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
11-Dec-2003


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