Title

The nicotinic acetylcholine receptor CHRNA5/A3/B4 gene cluster: dual role in nicotine addiction and lung cancer

Student Author(s)

Ma Reina D. Improgo; Michael D. Scofield

GSBS Program

Neuroscience

UMMS Affiliation

Graduate School of Biomedical Sciences, Program in Neuroscience; Graduate School of Biomedical Sciences, Interdisciplinary Graduate Program; Department of Psychiatry, Brudnick Neuropsychiatric Research Institute

Date

10-1-2010

Document Type

Article

Medical Subject Headings

Receptors, Nicotinic; Nerve Tissue Proteins; Nicotine; Tobacco Use Disorder; Lung Neoplasms

Disciplines

Life Sciences | Medicine and Health Sciences | Neuroscience and Neurobiology

Abstract

More than 1 billion people around the world smoke, with 10 million cigarettes sold every minute. Cigarettes contain thousands of harmful chemicals including the psychoactive compound, nicotine. Nicotine addiction is initiated by the binding of nicotine to nicotinic acetylcholine receptors, ligand-gated cation channels activated by the endogenous neurotransmitter, acetylcholine. These receptors serve as prototypes for all ligand-gated ion channels and have been extensively studied in an attempt to elucidate their role in nicotine addiction. Many of these studies have focused on heteromeric nicotinic acetylcholine receptors containing α4 and β2 subunits and homomeric nicotinic acetylcholine receptors containing the α7 subunit, two of the most abundant subtypes expressed in the brain. Recently however, a series of linkage analyses, candidate-gene analyses and genome-wide association studies have brought attention to three other members of the nicotinic acetylcholine receptor family: the α5, α3 and β4 subunits. The genes encoding these subunits lie in a genomic cluster that contains variants associated with increased risk for several diseases including nicotine dependence and lung cancer. The underlying mechanisms for these associations have not yet been elucidated but decades of research on the nicotinic receptor gene family as well as emerging data provide insight on how these receptors may function in pathological states. Here, we review this body of work, focusing on the clustered nicotinic acetylcholine receptor genes and evaluating their role in nicotine addiction and lung cancer.

Rights and Permissions

Citation: Improgo MR, Scofield MD, Tapper AR, Gardner PD (2010). The nicotinic acetylcholine receptor CHRNA5/A3/B4 gene cluster: Dual role in nicotine addiction and lung cancer. Prog Neurobiol. 92: 212-216. DOI: 10.1016/j.pneurobio.2010.05.003. Link to article on publisher's website

Related Resources

Link to article in PubMed

PubMed ID

20685379