Several mechanisms have been proposed for nicotine-induced up-regulation of nAChRs and it is quite likely that more than one mechanism is responsible for this phenomenon. There is controversy surrounding how this up-regulation of surface receptors occurs but it does not appear to be due to a change in subunit mRNA transcript levels (Marks et al., 1992; Bencherif et al., 1995; Ke et al., 1998) but has been proposed to be caused by increased translation or alterations in receptor assembly (Wang et al., 1998; Nashmi et al., 2003), trafficking (Harkness and Millar, 2002), and/or decreased receptor turnover (Wang et al., 1998). For example, nicotine has been shown to inhibit the turnover of cell-surface receptors of the α4β2* conformation. The authors, using cell line M10, demonstate that up-regulation of α4β2* nAChRs is due to an intrinsic property of these proteins and results from a conformational change of the receptors that makes their degradation and removal from the cell surface slower (Peng et al., 1994). Another possible mechanism is an increase in receptor trafficking to the cell surface upon long exposures to nicotine
