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

Liou, Horng-Huei; Hsu, Hao-Jui; Tsai, Yung-Fong; Shih, Chin-Yu; Chang, Yu‐Chia; Lin, Chun-Jung

doi:10.1016/j.lfs.2007.07.004

Cited by 13 publications

(17 citation statements)

References 42 publications

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“…Previous studies have demonstrated that nicotine inhibits OCT, such as OCT1-3 (SLC22A1-3) and OCTN1-2, in vitro (8,26) and may be a substrate of PMAT and MATE1 (27,28). There is conflicting evidence for the expression and function of Oct1 and/or Oct2 at the BBB in vitro (29,30). Moreover, nicotine has been suggested to interact in vivo and in vitro with Oct transporters at the BBB (29).…”

Section: Discussionmentioning

confidence: 99%

“…There is conflicting evidence for the expression and function of Oct1 and/or Oct2 at the BBB in vitro (29,30). Moreover, nicotine has been suggested to interact in vivo and in vitro with Oct transporters at the BBB (29). Our experiments found no evidence that these SLC carriers were involved in the BBB transport of nicotine, as it was not altered either by the deletion of Oct1-3 or by the inhibition of Oct, Mate1, Pmat, Octn, and choline transporters.…”

Section: Discussionmentioning

confidence: 99%

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

Cisternino

Chapy

André

et al. 2012

AAPS J

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Abstract. Nicotine, the main tobacco alkaloid leading to smoking dependence, rapidly crosses the bloodbrain barrier (BBB) to become concentrated in the brain. Recently, it has been shown that nicotine interacts with some organic cation transporters (OCT), but their influence at the BBB has not yet been assessed in vivo. In this study, we characterized the transport of nicotine at the mouse luminal BBB by in situ brain perfusion. Its influx was saturable and followed the Michaelis-Menten kinetics (K m 02.60 mM, V max 037.60 nmol/s/g at pH 7.40). At its usual micromolar concentrations in the plasma, most (79%) of the net transport of nicotine at the BBB was carrier-mediated, while passive diffusion accounted for 21%. Studies on knockout mice showed that the OCT Oct1-3, P-gp, and Bcrp did not alter [3 H]-nicotine transport at the BBB. Neither did inhibiting the transporters Mate1, Octn, or Pmat. The in vivo manipulation of intracellular and/or extracellular pH, the chemical inhibition profile, and the transstimulation experiments demonstrated that the nicotine transporter at the BBB shared the properties of the clonidine/proton antiporter. The molecular features of this proton-coupled antiporter have not yet been identified, but it also transports diphenhydramine and tramadol and helps nicotine cross the BBB at a faster rate and to a greater extent. The pharmacological inhibition of this nicotine/proton antiporter could represent a new strategy to reduce nicotine uptake by the brain and thus help curb addiction to smoking.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Cisternino

Chapy

André

et al. 2012

AAPS J

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“…Molecular and/or functional studies with in vitro BBB models have provided conflicting results about the presence of uptake2 carriers at the BBB; some concluded that Octs are not present (Friedrich et al, 2001). While functional Oct1 and/or Oct2 have been suggested at the BBB using in vitro models (Liou et al, 2007;Dickens et al, 2012) and in vivo by extracellular fluid microdialysis (Lin et al, 2010), these results may not be conclusive. The isolation and culture of endothelial cells for use in in vitro BBB models often leads to the dysregulation of transporters (Lyck et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Transport of Biogenic Amine Neurotransmitters at the Mouse Blood–Retina and Blood–Brain Barriers by Uptake1 and Uptake2

André

Saubaméa

Cochois-Guégan

et al. 2012

J Cereb Blood Flow Metab

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Uptake1 and uptake2 transporters are involved in the extracellular clearance of biogenic amine neurotransmitters at synaptic clefts. We looked for them at the blood-brain barrier (BBB) and bloodretina barriers (BRB), where they could be involved in regulating the neurotransmitter concentration and modulate/terminate receptor-mediated effects within the neurovascular unit (NVU). Uptake2 (Oct1-3/ Slc22a1-3, Pmat/Slc29a4) and Mate1/Slc47a1 transporters are also involved in the transport of xenobiotics. We used in situ carotid perfusion of prototypic substrates like-serotonin, and [ 3 H]-dopamine, changes in ionic composition and genetic deletion of Oct1-3 carriers to detect uptake1 and uptake2 at the BBB and BRB. We showed that uptake1 and uptake2 are involved in the transport of [ 3 H]-dopamine and [ 3 H]-MPP + at the blood luminal BRB, but not at the BBB. These functional studies, together with quantitative RT-PCR and confocal imaging, suggest that the mouse BBB lacks uptake1 (Net/Slc6a2, Dat/Slc6a3, Sert/Slc6a4), uptake2, and Mate1 on both the luminal and abluminal sides. However, we found evidence for functional Net and Oct1 transporters at the luminal BRB. These heterogeneous transport properties of the brain and retina NVUs suggest that the BBB helps protect the brain against biogenic amine neurotransmitters in the plasma while the BRB has more of a metabolic/endocrine role.

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“…The probe was stereotaxically implanted into the right side of the caudate putamen at the following coordinates: A-P + 0.6 mm and M-L − 1.6 mm from the bregma and D-V − 4 mm below the dura according to the stereotaxic atlas of Paxinos and Franklin (2004). Dialysis probes with a 2.5-mm-long dialysis surface were prepared for insertion into the brain according to the method described previously (Liou et al 2007). The relative recovery of rhodamine 123 was tested in each probe in vitro prior to use, and only probes with a recovery greater than 10% were used.…”

Section: In Vivo Microdialysis Studymentioning

confidence: 99%

“…The cells (1 × 10 6 ) were seeded in 75-cm 2 flasks coated with type I rat tail collagen (50 μg/ml; Sigma) and were grown routinely at 37°C according to the method described previously (Liou et al 2007;Yeh et al 2008), with the exception that the glucose concentration was replaced by either 5 mM or 25 mM. For experiments, cells were treated as follows: 100 nM insulin for 24 h, and 50 nM PMA (phorbol 12-myristate 13-acetate) for either 6 h or 72 h. After treatments, the cells were removed by 0.25% Trypsin/EDTA and suspended in 5 ml of 0.01 M Tris-HCl buffer (pH 7.4) containing a protease inhibitor cocktail (Roche, Germany).…”

Section: Cell Culture and Treatmentsmentioning

confidence: 99%

Change in P-glycoprotein and caveolin protein expression in brain striatum capillaries in New Zealand Obese mice with type 2 diabetes

Pan

Yin

et al. 2009

Life Sciences

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

Cited by 13 publications

References 42 publications

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

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

Transport of Biogenic Amine Neurotransmitters at the Mouse Blood–Retina and Blood–Brain Barriers by Uptake1 and Uptake2

Change in P-glycoprotein and caveolin protein expression in brain striatum capillaries in New Zealand Obese mice with type 2 diabetes

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