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Article: A purine-selective nucleobase/nucleoside transporter in PK15NTD cells

TitleA purine-selective nucleobase/nucleoside transporter in PK15NTD cells
Authors
Keywords[ 3H]guanine
Adenine
Adenosine
Cladribine
Issue Date2008
PublisherAmerican Physiological Society. The Journal's web site is located at http://intl-ajpregu.physiology.org
Citation
American Journal Of Physiology - Regulatory Integrative And Comparative Physiology, 2008, v. 294 n. 6, p. R1988-R1995 How to Cite?
AbstractNucleoside 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 K m values 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 IC 50 values of 68 ± 5 and 99 ± 10 μM, respectively. The nucleobase/nucleoside transporter was resistant to nitrobenzylthioinosine {6-[(4-nitrobenzyl) thiol]-9-±-D-ribofuranosylpurine}, dipyridamole, and dilazep, but was inhibited by papaverine, the organic cation transporter inhibitor decynium-22 (IC 50 of ∼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. Copyright © 2008 the American Physiological Society.
Persistent Identifierhttp://hdl.handle.net/10722/80323
ISSN
2015 Impact Factor: 3.168
2015 SCImago Journal Rankings: 1.663
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorHoque, KMen_HK
dc.contributor.authorChen, Len_HK
dc.contributor.authorLeung, GPHen_HK
dc.contributor.authorTse, CMen_HK
dc.date.accessioned2010-09-06T08:05:02Z-
dc.date.available2010-09-06T08:05:02Z-
dc.date.issued2008en_HK
dc.identifier.citationAmerican Journal Of Physiology - Regulatory Integrative And Comparative Physiology, 2008, v. 294 n. 6, p. R1988-R1995en_HK
dc.identifier.issn0363-6119en_HK
dc.identifier.urihttp://hdl.handle.net/10722/80323-
dc.description.abstractNucleoside 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 K m values 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 IC 50 values of 68 ± 5 and 99 ± 10 μM, respectively. The nucleobase/nucleoside transporter was resistant to nitrobenzylthioinosine {6-[(4-nitrobenzyl) thiol]-9-±-D-ribofuranosylpurine}, dipyridamole, and dilazep, but was inhibited by papaverine, the organic cation transporter inhibitor decynium-22 (IC 50 of ∼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. Copyright © 2008 the American Physiological Society.en_HK
dc.languageengen_HK
dc.publisherAmerican Physiological Society. The Journal's web site is located at http://intl-ajpregu.physiology.orgen_HK
dc.relation.ispartofAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiologyen_HK
dc.subject[ 3H]guanineen_HK
dc.subjectAdenineen_HK
dc.subjectAdenosineen_HK
dc.subjectCladribineen_HK
dc.titleA purine-selective nucleobase/nucleoside transporter in PK15NTD cellsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0363-6119&volume=294&spage=R1988&epage=1995&date=2008&atitle=A+purine-selective+nucleobase/nucleoside+transporter+in+PK15NTD+cellsen_HK
dc.identifier.emailLeung, GPH: gphleung@hkucc.hku.hken_HK
dc.identifier.authorityLeung, GPH=rp00234en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1152/ajpregu.00016.2008en_HK
dc.identifier.scopuseid_2-s2.0-47549116556en_HK
dc.identifier.hkuros143133en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-47549116556&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume294en_HK
dc.identifier.issue6en_HK
dc.identifier.spageR1988en_HK
dc.identifier.epageR1995en_HK
dc.identifier.isiWOS:000256438200027-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridHoque, KM=20436385200en_HK
dc.identifier.scopusauthoridChen, L=24471094500en_HK
dc.identifier.scopusauthoridLeung, GPH=35963668200en_HK
dc.identifier.scopusauthoridTse, CM=7103295076en_HK

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