Biomedical Engineering Reference
In-Depth Information
CH
3
CH
3
N
+
H
3
C
CH
3
N
+
H
3
C
CH
3
CH
3
CH
3
Tetramethylammonium (TMA)
Tetraethylammonium (TEA)
NH
2
NH
2
N
HO
N
OH
H
Dopamine
Histamine
NH
NH
N
H
3
C
N
N
NH
NH
2
NH
CH
3
H
3
C
Metformin Desipramine
FIGURE 2.3.
Representative substrates of organic cation transporters. OCTs are capable of
transporting a variety of structurally diverse substrates, including tetraalkylammonium com-
pounds (TMA, TEA), endogenous compounds (dopamine, histamine) and clinically important
drugs (desipramine, metformin).
Importantly, OCT orthologs from different species may exhibit differences in sub-
strate specificity. For example, OCT1 orthologs from human, rabbit, mouse, and
rat all transport the low-molecular-weight tetraalkylammonium compounds tetram-
ethylammonium (TMA) and TEA. In contrast to human and rabbit, rat and mouse
Oct1 do not transport the larger tetrapropylammonium (TPA) or tetrabutylammonium
(TBA),
26
suggesting that molecular mass or hydrophobicity may effect differences in
recognition of OCT substrates across species.
2.4. TISSUE DISTRIBUTION
Despite the similarities in structure and function, there are important differences in
the tissue distribution of mRNA transcripts of the OCTs in human tissues. OCT1
is expressed predominantly in human liver, with lower levels of expression in other
tissues.
4
,
9
OCT1 is thus characterized as a
liver-specific
OCT. Analogously, OCT2,
which is expressed almost exclusively in kidney, is described as the
kidney-specific
OCT
.
4
,
42
OCT3, also referred to as the
extraneuronal monoamine transporter
(EMT),
has a broad tissue distribution, with moderate levels of mRNA found in the aorta,
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