scholarly journals The human organic cation transporter OCT1 mediates high affinity uptake of the anticancer drug daunorubicin

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Emil Andreev ◽  
Nicolas Brosseau ◽  
Euridice Carmona ◽  
Anne-Marie Mes-Masson ◽  
Dindial Ramotar
Keyword(s):  
Anticancer Drug ◽  
Organic Cation ◽  
Organic Cation Transporter ◽  
High Affinity ◽  
High Affinity Uptake

A purine-selective nucleobase/nucleoside transporter in PK15NTD cells

2008 ◽  
Vol 294 (6) ◽  
pp. R1988-R1995 ◽  
Author(s):  
Kazi Mirajul Hoque ◽  
Linxi Chen ◽  
George P. H. Leung ◽  
Chung-Ming Tse
Keyword(s):  
Transport System ◽  
Mammalian Cells ◽  
Organic Cation ◽  
Organic Cation Transporter ◽  
Nucleoside Transport ◽  
Acidic Ph ◽  
Nucleoside Transporter ◽  
High Affinity ◽  
Naturally Occurring ◽  
Purine Analog

Nucleoside and nucleobase transporters are important for salvage of purines and pyrimidines and for transport of their analog drugs into cells. However, the pathways for nucleobase translocation in mammalian cells are not well characterized. We identified an Na-independent purine-selective nucleobase/nucleoside transport system in the nucleoside transporter-deficient PK15NTD cells. This transport system has 1,000-fold higher affinity for nucleobases than nucleosides with Kmvalues of 2.5 ± 0.7 μM for [3H]adenine, 6.4 ± 0.5 μM for [3H]guanine, 1.1 ± 0.1 mM for [3H]guanosine, and 4.2 ± 0.5 mM [3H]adenosine. The uptake of [3H]guanine (0.05 μM) was inhibited by other nucleobases and nucleobase analog drugs (at 0.5–1 mM in the order of potency): 6-mercaptopurine = thioguanine = guanine > adenine >>> thymine = fluorouracil = uracil. Cytosine and methylcytosine had no effect. Nucleoside analog drugs with modification at 2′ and/or 5 positions (all at 1 mM) were more potent than adenosine in competing the uptake of [3H]guanine: 2-chloro-2′-deoxyadenosine > 2-chloroadenosine > 2′3′-dideoxyadenosine = 2′-deoxyadenosine > 5-deoxyadenosine > adenosine. 2-Chloro-2′-deoxyadenosine and 2-chloroadenosine inhibited [3H]guanine uptake with IC50values of 68 ± 5 and 99 ± 10 μM, respectively. The nucleobase/nucleoside transporter was resistant to nitrobenzylthioinosine {6-[(4-nitrobenzyl) thiol]-9-β-d-ribofuranosylpurine}, dipyridamole, and dilazep, but was inhibited by papaverine, the organic cation transporter inhibitor decynium-22 (IC50of ∼1 μM), and by acidic pH (pH = 5.5). In conclusion, we have identified a mammalian purine-selective nucleobase/nucleoside transporter with high affinity for purine nucleobases. This transporter is potentially important for transporting naturally occurring purines and purine analog drugs into cells.

scholarly journals Functional expression of a high affinity mammalian hepatic choline/organic cation transporter

2000 ◽  
Vol 41 (11) ◽  
pp. 1841-1848 ◽  
Author(s):  
Christian J. Sinclair ◽  
Kenneth D. Chi ◽  
Veedamali Subramanian ◽  
Kristine L. Ward ◽  
Richard M. Green
Keyword(s):  
Organic Cation ◽  
Organic Cation Transporter ◽  
Functional Expression ◽  
High Affinity

scholarly journals Transport of carnitine and acetylcarnitine by carnitine/organic cation transporter (OCTN) 2 and OCTN3 into epididymal spermatozoa

Reproduction ◽  
2007 ◽  
Vol 134 (5) ◽  
pp. 651-658 ◽  
Author(s):  
Daisuke Kobayashi ◽  
Ikumi Tamai ◽  
Yoshimichi Sai ◽  
Kazuhiro Yoshida ◽  
Tomohiko Wakayama ◽  
...  
Keyword(s):  
Transport System ◽  
Organic Cation ◽  
Organic Cation Transporter ◽  
Selective Inhibition ◽  
Time Dependent ◽  
Immunofluorescence Analysis ◽  
Inhibition Study ◽  
High Affinity ◽  
Epididymal Spermatozoa

Carnitine and acetylcarnitine are important for the acquisition of motility and maturation of spermatozoa in the epididymis. In this study, we examined the involvement of carnitine/organic cation transporter (OCTN) in carnitine and acetylcarnitine transport in epididymal spermatozoa of mice. Uptake of both compounds by epididymal spermatozoa was time-dependent and partially Na+-dependent. Kinetic analyses revealed the presence of a high-affinity transport system in the spermatozoa, withKmvalues of 23.6 and 6.57 μM for carnitine and acetylcarnitine respectively in the presence of Na+. Expression of OCTN2 and OCTN3 in epididymal spermatozoa was confirmed by immunofluorescence analysis. The involvement of these two transporters in carnitine and acetylcarnitine transport was supported by a selective inhibition study. We conclude that both Na+-dependent and -independent carnitine transporters, OCTN2 and OCTN3, mediate the supply of carnitine and acetylcarnitine to epididymal spermatozoa in mice.

Organic cation transporter 3 ist im hepatischen Kupfermetabolismus involviert

2018 ◽  
Vol 56 (08) ◽  
pp. e250-e250
Author(s):  
S Guttmann ◽  
S Reinartz Groba ◽  
C Niemietz ◽  
V Sandfort ◽  
A Zibert ◽  
...  
Keyword(s):  
Organic Cation ◽  
Organic Cation Transporter ◽  
Organic Cation Transporter 3
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