Reporting in today's Early Edition of the August Proceedings of the National Academy of Sciences, researchers at the University of Texas at Austin and Stanford University describe a novel approach that may help scientists to better understand how alcohols and anesthetic drugs interact with certain brain proteins. The report also provides the strongest evidence to date that alcohols have specific protein binding sites.

R. Adron Harris, Ph.D., Director, Waggoner Center for Alcohol and Addiction Research, Institute for Cellular and Molecular Biology, University of Texas at Austin, with colleagues Maria Paola Mascia, Ph.D. (University of Texas) and James R. Trudell, Ph.D. (Stanford University), developed a way to attach an anesthetic analogue called propanethiol to amino acid residues at a specific site in glycine and GABAA receptors. GABA and glycine receptors are the primary mediators of inhibitory neurotransmission in the brain and spinal cord.

The new work adds weight to previous studies that suggested that alcohols and anesthetic drugs exert some of their effects by interacting with specific protein molecules in the brain. Propanethiol (and also propyl-methanethiosulfanate), the researchers found, irreversibly enhances receptor function and obviates the ability of other alcohols and anesthetics to potentiate receptor function.

"Today's report advances general medical understanding of the basic pharmacology of alcohols and anesthetics," said Enoch Gordis, M.D., Director of the National Institute on Alcohol Abuse and Alcoholism (NIAAA). "Accumulating knowledge of how beverage alcohol (ethanol) produces its anesthetic and intoxicating effects at these receptors may lead to new pharmacologic and behavioral interventions."

For years, prevailing wisdom held that, unlike drugs with a single site of action, alcohols and anesthetics acted on many nonspecific sites of the neuronal membrane. More recent research has shown that these compounds a
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Contact: Ann Bradley
abradley@willco.niaaa.nih.gov
301-443-3860
NIH/National Institute on Alcohol Abuse and Alcoholism
23-Jul-2000