Nicotine-mediated activation of signal transduction pathways

摘要

Activation of nicotinic acetylcholine receptors (nAChRs) results in depolarization and entry of calcium into neurons. These processes initiate signal transduction cascades likely to be important for changes in synaptic strength that may underlie the development of nicotine addiction. Nicotine can activate a number of protein kinases and phosphatases in vitro and in vivo, including protein kinases A and C and the MAP kinase pathway. Of particular interest are signalling molecules, such as the protein phosphatase calcineurin, that can be activated by calcium entry. In addition, chronic nicotine exposure can result in circuit level changes in quantity and activation of proteins involved in signal transduction. Transcription factors such as the cydic-AMP response element binding protein (CREB) are attractive candidates for initiating long-term changes downstream of nAChRs. A better understanding of the signalling pathways activated by nicotine admin-isttation will be critical in understanding the transition between nicotine exposure and addiction.