PMID- 10087507
OWN - NLM
STAT- MEDLINE
DCOM- 19990629
LR  - 20191103
IS  - 0968-7688 (Print)
IS  - 0968-7688 (Linking)
VI  - 15
IP  - 4
DP  - 1998 Oct-Dec
TI  - Molecular cloning, functional expression and chromosomal localization of a cDNA
      encoding a human Na+/nucleoside cotransporter (hCNT2) selective for purine
      nucleosides and uridine.
PG  - 203-11
AB  - Two Na(+)-dependent nucleoside transporters implicated in adenosine and uridine
      transport in mammalian cells are distinguished functionally on the basis of
      substrate specificity: CNT1 is selective for pyrimidine nucleosides but also
      transports adenosine; CNT2 (also termed SPNT) is selective for purine nucleosides
      but also transports uridine. Both proteins belong to a gene family that includes 
      the NupC proton/nucleoside symporter of E. coli. cDNAs encoding members of the
      CNT family have been isolated from rat tissues (jejunum, brain, liver; rCNT1 and 
      rCNT2/SPNT) and, most recently, human kidney (hCNT1 and hSPNT1). Here, the
      molecular cloning and functional characterization of a CNT2/SPNT-type transporter
      from human small intestine are described. The encoded 658-residue protein (hCNT2 
      in the nomenclature) had the same predicted amino acid sequence as human kidney
      hSPNT1, except for a polymorphism at residue 75 (Arg substituted by Ser), and was
      83 and 72% identical to rCNT2 and hCNT1, respectively. Sequence differences
      between hCNT2 and rCNT2 were greatest at the N-terminus. In Xenopus oocytes,
      recombinant hCNT2 exhibited the functional characteristics of a Na(+)-dependent
      nucleoside transporter with selectivity for adenosine, other purine nucleosides
      and uridine (adenosine and uridine K(m) app values 8 and 40 microM,
      respectively). hCNT2 transcripts were found in kidney and small intestine but,
      unlike rCNT2, were not detected in liver. Deoxyadenosine, which undergoes net
      renal secretion in humans, was less readily transported than adenosine. hCNT2
      also mediated small, but significant, fluxes of the antiviral purine nucleoside
      analogue 2',3'-dideoxyinosine. hCNT2 is, therefore potentially involved in both
      the intestinal absorption and renal handling of purine nucleosides (including
      adenosine), uridine and purine nucleoside drugs. The gene encoding hCNT2 was
      mapped to chromosome 15q15.
FAU - Ritzel, M W
AU  - Ritzel MW
AD  - Department of Physiology, University of Alberta, Edmonton, Canada.
FAU - Yao, S Y
AU  - Yao SY
FAU - Ng, A M
AU  - Ng AM
FAU - Mackey, J R
AU  - Mackey JR
FAU - Cass, C E
AU  - Cass CE
FAU - Young, J D
AU  - Young JD
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Mol Membr Biol
JT  - Molecular membrane biology
JID - 9430797
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Carrier Proteins)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Purine Nucleosides)
RN  - 0 (cif nucleoside transporter)
RN  - 4B9XT59T7S (Zidovudine)
RN  - 6L3XT8CB3I (Zalcitabine)
RN  - K3GDH6OH08 (Didanosine)
RN  - K72T3FS567 (Adenosine)
RN  - WHI7HQ7H85 (Uridine)
SB  - IM
SB  - X
MH  - Adenosine/metabolism
MH  - Amino Acid Sequence
MH  - Animals
MH  - Anti-HIV Agents/pharmacology
MH  - Carrier Proteins/*genetics/*metabolism
MH  - Chromosome Mapping
MH  - Chromosomes, Human, Pair 15
MH  - Cloning, Molecular
MH  - Didanosine/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Gene Expression Regulation, Developmental
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Intestine, Small/metabolism
MH  - Ion Transport/*physiology
MH  - Jejunum/metabolism
MH  - Kinetics
MH  - *Membrane Transport Proteins
MH  - Molecular Sequence Data
MH  - Purine Nucleosides/*metabolism
MH  - Rats
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sequence Homology, Amino Acid
MH  - Tissue Distribution
MH  - Uridine/*metabolism
MH  - Xenopus/embryology
MH  - Zalcitabine/pharmacology
MH  - Zidovudine/pharmacology
EDAT- 1999/03/24 00:00
MHDA- 1999/03/24 00:01
CRDT- 1999/03/24 00:00
PHST- 1999/03/24 00:00 [pubmed]
PHST- 1999/03/24 00:01 [medline]
PHST- 1999/03/24 00:00 [entrez]
AID - 10.3109/09687689709044322 [doi]
PST - ppublish
SO  - Mol Membr Biol. 1998 Oct-Dec;15(4):203-11. doi: 10.3109/09687689709044322.