Nicotine uptake

As shown in Fig. 1, the speed of nicotine uptake in venous blood following several forms of nicotine delivery varies widely, from that of the very slow pattern of nicotine appearance in the blood (several hours to peak level) produced by current transdermal nicotine medications to the explosive rise produced by tobacco smoke inhalation. Nicotine gum, lozenge, tablet, and vapor inhaler can provide more rapid delivery of nicotine than the patch, but the speed and amount obtained are constrained by use patterns. Smokeless tobacco products deliver their nicotine more rapidly than nicotine gum and with less physical effort, but are still slower than cigarettes in their nicotine dehvery. 

Nicotine increased DA levels both in vivo11,193 and in vitro. 94 196 Nicotine197 and its metabolites198 were found to both release and inhibit the reuptake of DA in rat brain slices, with uptake inhibition occurring at a lower concentration than that required for DA release. In addition, the (-) isomer was more potent than the (+) isomer.197 However, the effects of nicotine upon DA release and uptake were only apparent when brain slices were utilized because nicotine was unable to affect DA when a synaptosomal preparation was utilized.197 These results indicate that nicotine exerts its effects upon the DAT indirectly, most likely via nicotine acetylcholine receptors. This finding was supported by the results of Yamashita et al.199 in which the effect of nicotine on DA uptake was examined in PC 12 and COS cells transfected with rat DAT cDNA. Nicotine inhibited DA uptake in PC 12 cells that possess a nicotine acetylcholine receptor. This effect was blocked by the nicotinic antagonists hexamethonium and mecamylamine. Additionally, nicotine did not influence DA uptake in COS cells, which lack nicotinic acetylcholine receptors. 

Dwoskin, L.P., Leibee, L.L., Jewell, A.L., Fang, Z., and Crooks, P.A., Inhibition of [3H]dopamine uptake into rat striatal slices by quaternary V-methylated nicotine metabolites, Life Sci., 50, PL-223, 1992. 

Rausch, 1., Fefferman, M., Ladisich-Rogers, D., Menard, M. Effect of nicotine on human blood platelet serotonin uptake and efflux. Prog. Neuropsychopharmacol. Biol. Psychiatry. 13 907, 1989. 

Lobeline also increases basal release of norepinephrine, but norepinephrine release may be reduced at higher lobeline concentrations (Rao et al. 1997). Unlike acetylcholine, lobeline does not reduce the release of dopamine or norepinephrine by NMDA receptors, but it does block nicotine-induced release of norepinephrine from the locus coeruleus (Gallardo and Leslie 1998). Lobeline also evokes release of serotonin, which is mediated by uptake transporters and unaffected by mecamylamine (Lendvai et al. 1996). 

Teng L, Crooks PA, Sonsalla PK, Dwoskin LP. (1997). Lobeline and nicotine evoke [3H]overflow from rat striatal slices preloaded with [3H]dopamine differential inhibition of synaptosomal and vesicular [3H]dopamine uptake. J Pharmacol Exp Ther. 280(3) 1432-44. 

In vitro stndies have shown that there are distinct transport systems for both baso-lateral and apical uptake of nicotine (Takami et al. 1998). Nicotine has been shown to be actively transported by kidney cells, most likely by the organic ion transporter OCT2 (Zevin et al. 1998 Urakami et al. 1998). Cimetidine decreases renal clearance of nicotine by 47% in nonsmoking volunteers (Bendayan et al. 1990). This is consistent with the inhibition of basolateral uptake by cimetidine detected in vitro. Mecamylamine reduces renal clearance of nicotine in smokers dosed with intra-venons nicotine when urine is alkalinized, but not when nrine is acidified (Zevin et al. 2000). 

Potentials problems with the use of hair include a strong influence of hair pigmentation on nicotine and cotinine binding and uptake (Dehn et al. 2001). Nicotine and cotinine are bound to melanin. As a result, dark hair binds much more nicotine than does blond or white hair. This makes comparison across individuals difficult. Also, hair is exposed to nicotine and cotinine from sweat and from sebaceous gland secretions, and to nicotine from environmental tobacco smoke exposure. Washing the hair before analysis may reduce this problem of environmental contamination, but it is not likely to remove all environmental nicotine and cotiiune. 

Rowell PP, Hurst HE, Marlowe C, Bennett BD (1983) Oral administration of nicotine its uptake and distribution after chronic administration to mice. J Pharmacol Methods 9 249-261 Russell MAH (1990) Nicotine intake and its control over smoking. In Wonnacott S, Russell MAH, Stolerman IP (eds) Nicotine psychopharmacology, molecular, cellular and behavioural aspects. Oxford University Press, New York, pp 374 18... 

Functional interactions between the nicotinic and cannabinoid systems have been proposed (Cohen et al. 2002) and several studies have tested the applicability of these ideas to nicotine discrimination. However cannabinoid agonists acting at cannabinoid CBi and CB2 receptors have failed to generalise with nicotine (Zaniewska et al. 2006). Results with the anandamide uptake and fatty acid amide hydrolase inhibitors AM-404 and URB 597, that elevate brain concentrations of endogenous cannabinoids, were also negative. Furthermore, neither the CBi receptor... 

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