Kenneth J. Kellar, P
Professor and Vice-Chair
Georgetown University Medical Center
NE 413 Med/Dent Building
Washington, DC 20057
Phone: 202 687-1032
Fax : 202 687-5390
Regulation and pharmacology of neuronal nicotinic acetylcholine receptors and their roles in neuronal physiology.
It has been reported that nicotine affects the cognitive skills of men and women in different ways, improving subjective confidence in women and verbal task completion in men. My laboratory studies the pharmacology and regulation of neuronal nicotinic acetylcholine receptors. These receptors are ligand-gated ion channels found throughout the CNS and autonomic nervous systems, where they mediate many actions of acetylcholine. In the autonomic nervous system, they mediate fast neurotransmission at virtually all known autonomic ganglia. In the CNS, they are often found presynaptically on axons of other neurons, such as dopamine and GABA neurons, where they influence release of these other neurotransmitters. The nicotinic receptors exist as different subtypes based on their subunit composition. Each subtype has distinguishing biophysical characterisitics (e.g., ion conductances and time constants), and some have distinguishing pharmacological characterisitics as well. These receptors are thought to play an important role in reward pathways, release of some pituitary hormones, cognition and mental focus; in fact, there are attempts now underway to determine if nicotinic agonists can be useful in disorders of cognition. In addition, these receptors are the targets of nicotine, and one of the major subtypes in brain is increased upon repeated exposure to nicotine, suggesting it is involved in nicotine addiction.
- Meyer EL, Xiao Y and Kellar KJ: Agonist regulation of rat a3ß4 nicotinic acetylcholine receptors stably expressed in HEK 293 cells. Mol. Pharmacol. 60:568-576, 2001.
- Xiao Y, Smith-Carliss R, Caruso FS and Kellar KJ: Blockade of a3ß4 nicotinic receptor function by methadone, its metabolites, and structural analogs. J. Pharmacol. Exp. Ther. 299:366-371, 2001.
- Perry DC, XiaoY, Nguyen HN, Musachio JL, Dávila-García MI and Kellar KJ: Measuring nicotinic receptors with characteristics of a4ß2, a3ß2 and a3ß4 subtypes in rat tissues by autoradiography. J. Neurochem. 82:468-471, 2002.
- Dávila-García MI, Musachio JM and Kellar KJ: Chronic nicotine administration does not increase nicotinic receptors labeled by [125I]epibatidine in adrenal gland, superior cervical ganglia, pineal or retina. J. Neurochem. In press.
- Fitch RW, Xiao Y, Kellar KJ and Daly JW: Membrane potential fluorescence: a rapid and highly sensitive assay for nicotinic receptor channel function. Proc. Natl Acad. Sci (USA). In press