Pergamon 0024-3205(94)00136-7 Life Sciences, Vol. 55, No. 5, pp. PL 91-98, 1994 Copyright © 1994 Elsevier Science Ltd Printed in the USA. All rights re.fred OO24-32O5/94 $6.OO + .00 PHARMACOLOGY LETTERS Accelerated Communication NICOTINE STIMULATION OF NERVE GROWTH FACTOR RECEPTOR EXPRESSION Alvin V. Terry, Jr. 1,3 and Mark S.F. Clarke 2 1. Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, GA 30912 2. Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta, GA 30912 3. Department of Veterans Affairs Medical Center, Augusta, GA 30912 (Submitted March 29, 1994; accepted April 26, 1994; received in final form May 20, 1994) Abstract. Previous studies have suggested that nicotine may have beneficial actions in neurodegenerative disease models. The purpose of the experiments described in this study was to determine whether the long lasting and beneficial effects of nicotine observed previously could be expressed through actions upon nerve growth factor (NGF) receptors. Using a differentiated PC-12 neuronal cell model, we have detected an increase in expression of cell surface NGF receptor protein after acute exposure to nicotine in the micromolar range. In addition, we have also observed a persistent effect upon NGF receptor expression which lasted even after nicotine (nanomolar range) was removed from the tissue culture medium. This increase in cell surface NGF receptor protein was blocked in the presence of mecamylamine, indicating that this effect is likely nicotinic receptor mediated. These results are consistent with the hypothesis that the lasting and beneficial actions of nicotine previously observed in vivo may involve an indirect effect upon the level of neuronal cell surface NGF receptor expression. Our observations offer one possible mechanism for a potential neurotrophic effect of nicotine. Key Words: nicotine, nerve growth factor, Alzheimer' s disease, Parkinson' s disease Introduction The central nicotinic-cholinergic system is now known to play an important role in cognitive function (for review: 1). Neurodegenerative diseases which involve marked reductions in cognitive ability, such as Alzheimer's Disease and Parkinson's Disease, have been associated with substantial reductions in central nicotinic receptors (2). In addition, the naturally occurring plant alkaloid, nicotine, has proven beneficial in a number of models of learning and memory. Recent examples of nicotine enhanced cognitive function include studies in rodents (3), non-human primates (4) as well as in human patients (5). Furthermore, mecamylamine, a nicotinic antagonist has been shown to cause cognitive deficits in rodents (6), non-human primates (7) and humans (8). Alvin V. Terry, Jr., Ph.D., Dept. of Pharmacology/Toxicology, MCG, Augusta, GA 30912