The National Institutes of Health (NIH) has awarded a scientist at the Barrow Neurological Institute at St. Joseph's Hospital and Medical Center a $275,000 grant to study a rare brain receptor that may be a new smoking cessation target.

Throughout the next two years, researcher Paul Whiteaker, PhD, and other scientists in the Barrow Neurochemistry Laboratory will use the NIH Exploratory/Developmental grant to create an artificial system to produce the rare a6 nicotinic receptors normally found in the brain. They will then be able to study the way potential therapeutic drugs interact with this key receptor that has been implicated in diseases ranging from addictions to Parkinson's disease. Previous studies have been hindered because of the a6 receptors' scarcity and the complexity in studying them in isolation from other nicotinic receptor types.

"By creating this artificial cell line we will have the opportunity to produce pure populations of these receptors on demand, examine drug interactions quickly and in great detail, and study specifically how a6 receptors interact with potential new smoking cessation therapies," says Dr. Whiteaker. "If we can precisely target the neurons that express a6 receptors without involving others, we can develop treatments that may be more effective and have fewer side effects than current smoking treatments."

Dr. Whiteaker said that the a6 receptor has a very restricted distribution in the brain and is particularly concentrated on cells that produce the neurotransmitter dopamine. Activation of a subset of these cells has been implicated in the establishment and maintenance of addictive behaviors, including smoking. Loss of related dopamine-producing cells underlies the neurodegenerative condition Parkinson's disease. The grant also will potentially enhance research into the relationship between nicotinic receptor function and Parkinson's disease.

Barrow's researchers have received worldwide recognition for their study of nicotinic receptors. These receptors are located throughout the brain and body and act as "molecular switches" to connect nerve cell circuits involved in essential functions ranging from vision and memory to the control of heart rate and muscle movement. Defects in this group of receptors or their loss causes diseases such as myasthenia gravis and epilepsy and can contribute to Alzheimer's disease, Parkinson's disease, and schizophrenia. They also contribute to nicotine dependence and the drive to use tobacco.

Lynne Reaves
St. Joseph's Hospital and Medical Center

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