Nicotine's ability to selectively activate its receptors in the brain, but not muscle, is explained in a study in Nature. The findings solve the chemical mystery of nicotine addiction.
If nicotine activated its receptors in muscles as potently as in the brain, smoking would cause intolerable and perhaps fatal muscle contractions - so how does the chemical discriminate? Dennis Dougherty and colleagues find that it's all due to a specific interaction that only occurs in the brain, between the positive charge of nicotine and a specific aromatic amino acid on the brain receptor. This 'cation-pi' interaction doesn't happen in muscle, even though the binding sites for nicotine have the same overall structure. The difference is probably due to a subtle difference in the binding pockets, which allows nicotine to bind more tightly to the neuronal receptor.
Dennis Dougherty (California Institute of Technology, Pasadena, CA, USA)
Abstract available online.(C) Nature press release.
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