Speaker: Amina Woods, National Institute of Drug Abuse (NIDA), IRP, NIH, 5500 Nathan Shock Drive, Baltimore, MD 21224

Topic: Targeted Proteomics: A Study of the Interaction of a Ganglionic Blocker with the Neuronal Nicotinic Acetylcholine Receptor - Video (running time 00:49:28) ^*

Place: Building 426, Conference Room, NCI-Frederick, Frederick, MD

Time: Tuesday, March 19, 2002, at 2:00 PM

Abstract: Proteomics is one of the most popular and thought after field of research in the bio-medical research field. The study of proteins is not exactly new. However the new way of investigating proteins structure and function is. The new approach can glean a spectacular amount of information. It also requires an enormous investment of resources and personnel that are often unavailable to the average researcher. A more modest approach was used to answer the question "Why does Chlorisondamine [a bis-quaternary compound], a nicotinic antagonist, exert a long lasting blockade of the brain nicotinic acetylcholine receptors?" First, all information available on the structure of both the receptor and the blocker were investigated. Second, the amino acid composition of each isoform of the receptor were carefully perused. Third, possible epitopes for the interaction were found. Peptides with similar or identical amino acid sequence were acquired and tested, as well as other quaternary ammonium compounds. The administration of chlorisondamine does not interfere with acetylcholine or nicotine binding and does not result in a decrease in the number of nicotinic cholinergic receptors or neuronal degradation. These findings suggest that chlorisondamine is a non-competitive functional antagonist and that the binding does not happen at the Acetylcholine binding site. Once all results were compiled, the data suggest that chlorisondamine interacts with a cytoplasmic epitope of one of the isoform of the nicotinic receptor, through a combination of electrostatic and cation-pi interactions. The next step will involve in vivo experiments using the knowledge obtained to confirm the data obtained.

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