Functional expression of nicotine influx transporter in A549 human alveolar epithelial cells

Tega, Yuma; Yuzurihara, Chihiro; Kubo, Yoshiyuki; Akanuma, Shin‐ichi; Ehrhardt, Carsten; Hosoya, Ken‐ichi

doi:10.1016/j.dmpk.2015.11.006

Cited by 12 publications

(10 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The K m values are similar among these cells (Table 1), and nicotine transport was inhibited by hydrophobic cationic drugs such as pyrilamine and verapamil, whereas typical substrates of the above organic cation transporters such as tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP + ), and Lcarnitine had little effect on nicotine transport [26][27][28] (Table 2). These findings suggest that a novel organic cation transporter, which has not yet been identified, may play a significant role in nicotine transport in the lung, liver, and inner blood-retinal barrier (Fig.…”

Section: Transport Mechanism Of Nicotine In Tis-suesmentioning

confidence: 89%

“…Recent studies have clarified that nicotine is transported via carrier-mediated transport processes in human alveolar epithelial cell line (A549) and isolated rat hepatocytes, and immortalized rat retinal capillary endothelial cell line (TR-iBRB2), which are in vitro models of the lung, liver, and inner blood-retinal barrier, respectively. [26][27][28] The kinetic parameters of nicotine transport in these cells are displayed in Table 1.…”

Section: Transport Mechanism Of Nicotine In Tis-suesmentioning

confidence: 99%

“…[31][32][33] In humans, it has been reported that tobacco smoking causes a rapid raise of nicotine concentration in the brain, where the concentration reaches more than This table was prepared by reference to previous reports. [26][27][28]35) [26][27][28]35) 50% of its maximum level within 15 s after a single puff from cigarettes. 34) To enter the brain, it is considered that nicotine rapidly crosses the BBB, which is formed by tight-junction of brain capillary endothelial cells.…”

Section: Influx and Efflux Transport Of Nico-tine Across The Bbbmentioning

confidence: 99%

See 2 more Smart Citations

Impact of Nicotine Transport across the Blood–Brain Barrier: Carrier-Mediated Transport of Nicotine and Interaction with Central Nervous System Drugs

Tega

Yamazaki

Akanuma

et al. 2018

Biological & Pharmaceutical Bulletin

Self Cite

View full text Add to dashboard Cite

Nicotine, an addictive substance, is absorbed from the lungs following inhalation of tobacco smoke, and distributed to various tissues such as liver, brain, and retina. Recent in vivo and in vitro studies suggest the involvement of a carrier-mediated transport process in nicotine transport in the lung, liver, and inner blood-retinal barrier. In addition, in vivo studies of influx and efflux transport of nicotine across the blood-brain barrier (BBB) revealed that blood-to-brain influx transport of nicotine is more dominant than brain-to-blood efflux transport of nicotine. Uptake studies in TR-BBB13 cells, which are an in vitro model cell line of the BBB, suggest the involvement of H/organic cation antiporter, which is distinct from typical organic cation transporters, in nicotine transport at the BBB. Moreover, inhibition studies in TR-BBB13 cells showed that nicotine uptake was significantly reduced by central nervous system (CNS) drugs, such as antidepressants, anti-Alzheimer's disease drugs, and anti-Parkinson's disease drugs, suggesting that the nicotine transport system can recognize these molecules. The cumulative evidence would be helpful to improve our understanding of smoking-CNS drug interaction for providing appropriate medication.

show abstract

Section: Transport Mechanism Of Nicotine In Tis-suesmentioning

confidence: 89%

Section: Transport Mechanism Of Nicotine In Tis-suesmentioning

confidence: 99%

Section: Influx and Efflux Transport Of Nico-tine Across The Bbbmentioning

confidence: 99%

See 1 more Smart Citation

Impact of Nicotine Transport across the Blood–Brain Barrier: Carrier-Mediated Transport of Nicotine and Interaction with Central Nervous System Drugs

Tega

Yamazaki

Akanuma

et al. 2018

Biological & Pharmaceutical Bulletin

Self Cite

View full text Add to dashboard Cite

show abstract

“…Nicotine absorption was reduced by hydrophobic cationic drugs such as verapamil and pyrilamine, whereas typical substrates and inhibitors of organic cation transporters did not show inhibitory effect. 82 The transport mechanism of nicotine in alveolar epithelial cells shows great similarity to that in a brain capillary endothelial cell line in vitro. 83 This evidence suggests that the newly identified organic cation transport system is involved in nicotine transport process in lung and the blood-brain barrier.…”

Section: Implications Of the Carrier-mediated Transport Of Nicotine Imentioning

confidence: 98%

Current Progress Toward a Better Understanding of Drug Disposition Within the Lungs: Summary Proceedings of the First Workshop on Drug Transporters in the Lungs

Ehrhardt

Bäckman

Couet

et al. 2017

Journal of Pharmaceutical Sciences

Self Cite

View full text Add to dashboard Cite

The School of Pharmacy and Pharmaceutical Sciences at Trinity College Dublin hosted the "1 Workshop on Drug Transporters in the Lungs" in September 2016 to discuss the impact of transporters on pulmonary drug disposition and their roles as drug targets in lung disease. The workshop brought together about 30 scientists from academia and pharmaceutical industry from Europe and Japan and addressed the primary questions: What do we know today, and what do we need to know tomorrow about transporters in the lung? The 3 themes of the workshop were: (1) techniques to study drug transporter expression and actions in the lungs; (2) drug transporter effects on pulmonary pharmacokinetics-case studies; and (3) transporters as drug targets in lung disease. Some of the conclusions of the workshop were: suitable experimental models that allow studies of transporter effects are available; data from these models convincingly show a contribution of both uptake and efflux transporters on pulmonary drug disposition; the effects of transporters on drug lung PK is now better conceptualized; some transporters are associated with lung diseases. However, more work is needed to establish which of the available models best translate to the clinical situation.

show abstract

“…identity) has not yet been determined, e.g. those for psychoactive alkaloids such as cocaine [210] and nicotine [211][212][213][214][215] and opioids [216; 217]. Of course many transporters are known in the producer plants themselves [162][163][164].…”

Section: Natural Products That Are Nutrients or Bioactive Drugs Must mentioning

confidence: 99%

Consensus rank orderings of molecular fingerprints illustrate the ‘most genuine’ similarities between marketed drugs and small endogenous human metabolites, but highlight exogenous natural products as the most important ‘natural’ drug transporter substrates

O’Hagan

Kell

2017

Preprint

View full text Add to dashboard Cite

We compare several molecular fingerprint encodings for marketed, small molecule drugs, and assess how their rank order varies with the fingerprint in terms of the Tanimoto similarity to the most similar endogenous human metabolite as taken from Recon2. For the great majority of drugs, the rank order varies very greatly depending on the encoding used, and also somewhat when the Tanimoto similarity (TS) is replaced by the Tversky similarity. However, for a subset of such drugs, amounting to some 10% of the set and a Tanimoto similarity of ~0.8 or greater, the similarity coefficient is relatively robust to the encoding used. This leads to a metric that, while arbitrary, suggests that a Tanimoto similarity of 0.75-0.8 or greater genuinely does imply a considerable structural similarity of two molecules in the drug-endogenite space. Although comparatively few (<10% of) marketed drugs are, in this sense, robustly similar to an endogenite, there is often at least one encoding with which they are genuinely similar (e.g. TS > 0.75). This is referred to as the Take Your Pick Improved Cheminformatic Analytical Likeness or TYPICAL encoding, and on this basis some 66% of drugs are within a TS of 0.75 to an endogenite.We next explicitly recognise that natural evolution will have selected for the ability to transport dietary substances, including plant, animal and microbial 'secondary' metabolites, that are of benefit to the host. These should also be explored in terms of their closeness to marketed drugs. We thus compared the TS of marketed drugs with the contents of various databases of natural products. When this is done, we find that some 80% of marketed drugs are within a TS of 0.7 to a natural product, even using just the MACCS encoding. For patterned and TYPICAL encodings, 80% and 98% of drugs are within a TS of 0.8 to (an endogenite or) an exogenous natural product. This implies strongly that it is these exogeneous (dietary and medicinal) natural products that are more to be seen as the 'natural' substrates of drug transporters (as is recognised, for instance, for the solute carrier SLC22A4 and ergothioneine). This novel analysis casts an entirely different light on the kinds of natural molecules that are to be seen as most like marketed drugs, and hence potential transporter substrates, and further suggests that a renewed exploitation of natural products as drug scaffolds would be amply rewarded.

show abstract

Functional expression of nicotine influx transporter in A549 human alveolar epithelial cells

Cited by 12 publications

References 13 publications

Impact of Nicotine Transport across the Blood–Brain Barrier: Carrier-Mediated Transport of Nicotine and Interaction with Central Nervous System Drugs

Impact of Nicotine Transport across the Blood–Brain Barrier: Carrier-Mediated Transport of Nicotine and Interaction with Central Nervous System Drugs

Current Progress Toward a Better Understanding of Drug Disposition Within the Lungs: Summary Proceedings of the First Workshop on Drug Transporters in the Lungs

Consensus rank orderings of molecular fingerprints illustrate the ‘most genuine’ similarities between marketed drugs and small endogenous human metabolites, but highlight exogenous natural products as the most important ‘natural’ drug transporter substrates

Contact Info

Product

Resources

About