PMID- 10385678
OWN - NLM
STAT- MEDLINE
DCOM- 19990722
LR  - 20190607
IS  - 0026-895X (Print)
IS  - 0026-895X (Linking)
VI  - 56
IP  - 1
DP  - 1999 Jul
TI  - Selective substrates for non-neuronal monoamine transporters.
PG  - 1-10
AB  - The recently identified transport proteins organic cation transporter 1 (OCT1),
      OCT2, and extraneuronal monoamine transporter (EMT) accept dopamine,
      noradrenaline, adrenaline, and 5-hydroxytryptamine as substrates and hence
      qualify as non-neuronal monoamine transporters. In the present study, selective
      transport substrates were identified that allow, by analogy to receptor agonists,
      functional discrimination of these transporters. To contrast efficiency of solute
      transport, stably transfected 293 cell lines, each expressing a single
      transporter, were examined side by side in uptake experiments with radiolabeled
      substrates. Normalized uptake rates indicate that tetraethylammonium, with a rate
      of about 0.5 relative to 1-methyl-4-phenylpyridinium (MPP+), is a good substrate 
      for OCT1 and OCT2. It was not, however, accepted as substrate by EMT. Choline was
      transported exclusively by OCT1, with a rate of about 0.5 relative to MPP+.
      Histamine was a good substrate with a rate of about 0.6 relative to MPP+ for OCT2
      and EMT, but was not transported by OCT1. Guanidine was an excellent substrate
      for OCT2, with a rate as high as that of MPP+. Transport of guanidine by OCT1 was
      low, and transport by EMT was negligible. With the guanidine derivatives
      cimetidine and creatinine, a pattern strikingly similar to guanidine was
      observed. Collectively, these substrates reveal key differences in solute
      recognition and turnover and thus challenge the concept of "polyspecific" organic
      cation transporters. In addition, our data, when compared with previous studies, 
      suggest that OCT2 corresponds to the organic cation/H+ antiport mechanism in
      renal brush-border membrane vesicles, and that EMT corresponds to the
      guanidine/H+ antiport mechanism in membrane vesicles from placenta and intestine.
FAU - Grundemann, D
AU  - Grundemann D
AD  - Department of Pharmacology, University of Heidelberg, Heidelberg, Germany.
      dirk.gruendemann@urz.uni-heidelberg.de
FAU - Liebich, G
AU  - Liebich G
FAU - Kiefer, N
AU  - Kiefer N
FAU - Koster, S
AU  - Koster S
FAU - Schomig, E
AU  - Schomig E
LA  - eng
SI  - GENBANK/Y13154
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Pharmacol
JT  - Molecular pharmacology
JID - 0035623
RN  - 0 (Carrier Proteins)
RN  - 0 (DNA, Complementary)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Neuropeptides)
RN  - 0 (Organic Cation Transport Proteins)
RN  - 0 (Organic Cation Transporter 1)
RN  - 0 (Organic Cation Transporter 2)
RN  - 0 (SLC22A2 protein, human)
RN  - 0 (Slc22a2 protein, rat)
RN  - 0 (Vesicular Biogenic Amine Transport Proteins)
RN  - 820484N8I3 (Histamine)
RN  - JU58VJ6Y3B (Guanidine)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Biological Transport
MH  - Carrier Proteins/chemistry/genetics/*metabolism
MH  - Cells, Cultured
MH  - DNA, Complementary/genetics
MH  - Guanidine/analogs & derivatives/metabolism
MH  - Histamine/metabolism
MH  - Humans
MH  - Membrane Glycoproteins/*metabolism
MH  - Membrane Proteins/*metabolism
MH  - *Membrane Transport Proteins
MH  - Molecular Sequence Data
MH  - *Neuropeptides
MH  - *Organic Cation Transport Proteins
MH  - Organic Cation Transporter 1
MH  - Organic Cation Transporter 2
MH  - Rats
MH  - Sequence Homology, Amino Acid
MH  - Vesicular Biogenic Amine Transport Proteins
EDAT- 1999/07/01 00:00
MHDA- 1999/07/01 00:01
CRDT- 1999/07/01 00:00
PHST- 1999/07/01 00:00 [pubmed]
PHST- 1999/07/01 00:01 [medline]
PHST- 1999/07/01 00:00 [entrez]
AID - 10.1124/mol.56.1.1 [doi]
PST - ppublish
SO  - Mol Pharmacol. 1999 Jul;56(1):1-10. doi: 10.1124/mol.56.1.1.