Nicotine Transport in a Human Choriocarcinoma Cell Line (JAR)

Abstract

Smoking is a major health problem in pregnancy resulting in intrauterine growth retardation and birth complications. Nicotine, a toxic component of cigarette smoke, interferes with amino acid transport in the placenta and stimulates catecholamine release resulting in uteroplacental vasoconstriction. Transplacental transport of nicotine may be an important determinant of placental and fetal exposure. Our aim was to determine the mechanism of nicotine transport in the human choriocarcinoma cell line, JAR, as a model for the placenta. JAR cells were subcultured in 12-well plates following trypsinization at a seeding density of 0.5 x 10(6) cells/well (1.3 x 10(5) cells/cm2). Uptake studies of [3H]nicotine were carried out in JAR cell monolayers on day 2 after plating. [3H]Nicotine uptake was saturable (Km 156 microM), sensitive to temperature, and inhibited by unlabeled nicotine and various organic cations including mecamylamine and quinidine, but not by guanidine, tetraethylammonium (TEA), or neurotransmitters. Counterflux of [3H]nicotine uptake was produced by unlabeled nicotine and mecamylamine but not by cotinine or acetylcholine, consistent with a carrier-mediated transport process. The uptake could be driven by an inside-negative membrane potential or by an outwardly directed pH gradient. This is the first demonstration of a carrier-mediated transport mechanism for nicotine in a human cell line. This transport mechanism may have implications to the disposition of nicotine in the human placenta.

The effect of a series of organic cations upon the plasmalemmal serotonin transporter, SERT

“…The diuretic amiloride is known to decrease the placental uptake of the organic cations choline (Grassl, 1994) and guanidine (Zevin et al, 1997). However, in the present study, both guanidine and choline did not modify 3 H-5HT transport by JAR cells.…”

Coexistence of Passive and Proton Antiporter-Mediated Processes in Nicotine Transport at the Mouse Blood–Brain Barrier

“…A similar transporter has also been found in BBB cell lines, where it transports oxycodone, diphenhydramine, and codeine (33)(34)(35). An analogous nicotine/proton antiporter has also been characterized in kidney tubules, Caco-2, JAR, and LLC-PK1 cell lines (8,36,37). Many cationic organic drugs, such as clonidine, diphenhydramine, and MDMA, are similarly transported by a proton antiporter in Caco-2 cells (38)(39)(40).…”

Interaction between nicotine and MPTP/MPP+ in rat brain endothelial cells

“…Consistently, nicotine was detected in both blood and brain at the first collection interval in the current study. Although nicotine is considered to diffuse passively across the bloodbrain barrier (Hukkanen et al, 2005), studies from cell lines, including Caco-2 cells, LLK-PK1 cells, and JAR cells, showed that nicotine can be transported by a carrier-mediated process, of which the K m values ranged from 156 μM to 910 μM (Takami et al, 1998;Zevin et al, 1998;Fukada et al, 2002). It was also suggested that nicotine can interact with the renal OCT system in isolated renal tissues (Wong et al, 1992).…”