Biomedical Engineering Reference
In-Depth Information
presence of Na
+
. In addition, as suggested by electrophysiological studies, hOCTN2
is probably able to transport L-lysine and L-methionine under the same transport
conditions. Furthermore, human, rat, and mouse OCTN2 are able to translocate or
interact with various organic cations (e.g., TEA, pyrilamine, quinidine, verapamil,
choline) in a Na
+
- independent fashion.
16
-
18
,
25
Ohashi et al.
26
have determined that the TEA uptake by hOCTN2 has a
K
m
of
around 0.3
M. It has also been established that carnitine uptake by hOCTN2 was
competitively inhibited by TEA.
19
,
26
Other studies have shown that in the pres-
ence of Na
+
, carnitine uptake via OCTN2 is inhibited by other organic cations or
weak bases [e.g., nicotine, MPTP [1-methyl 4-phenyl 1, 2, 3, 6-tetrahydropyridine],
procainamide, quinine, metamphetamine, emetine, clonidine, cimetidine], zwitteri-
ons (cephaloridine, cefepime, cefoselis), and noncharged compounds (e.g., corti-
costerone, aldosterone).
16
,
18
,
24
,
27
The IC
50
values for cephaloridine, cephepime, and
cefoselis were 0.23, 1.7, and 6.4 mM, respectively. The removal of Na
+
decreases the
affinity for cephaloridine but not for cefepime and cefoselis.
24
Therefore, it is likely
that the binding of carnitine and cations occurs within one binding pocket.
μ
Tissue Distribution and Cellular Membrane Localization
Our recent studies have
demonstrated the expression and localization of this transporter in human placenta
and Caco-2 cells.
3
,
28
In an earlier study we had shown the presence of OCTN2 on
the apical membrane of small intestine and renal tubules.
1
In addition to intestine,
OCTN2 exhibited abundant expression in the stomach, colon, and rectum.
29
OCTN2,
also present in the brush border membrane of renal proximal tubules in the rat and
mouse,
9
participates in absorption and secretion of organic cations in the small intes-
tine and kidney. Mouse OCTN2 can translocate organic cations in either direction,
as exemplified by
trans
-stimulation of carnitine uptake by TEA as well as of TEA
efflux by carnitine.
25
Japanese researchers have demonstrated significant contribu-
tions of OCTN2 to the renal excretion of TEA by injecting radiolabeled TEA into
control mice and juvenile visceral steatosis (JVS) mice that suffer from a homozy-
gous loss-of-function mutation of OCTN2.
25
,
30
-
32
Secretion of TEA was reduced
by 50% in JVS mice compared to controls, and accumulation of TEA in the kid-
ney was increased by 150%.
25
Xuan et al.
13
have suggested that OCTN2 may be
responsible for carnitine transport across the spermatozoan plasma membrane. They
detected the expression of a 63-kDa OCTN2 protein in sperm which showed a high-
affinity carnitine transport, with a
K
m
value of 3.4
μ
M. This is very similar to the
K
m
values of 2 to 6
M observed for high-affinity carnitine transport in kidney,
skeletal muscle, heart, placenta, and cultured skin fibroblasts. Kobayashi et al.
33
have
demonstrated that the high-affinity carnitine transporter OCTN2, which is localized
at the basolateral membrane of epididymal epithelial cells, mediates carnitine supply
into those cells from the systemic circulation as the first step of permeation from
blood to spermatozoa. Another recent study
34
μ
reported the expression and localiza-
tion of OCTN2 in the
-cells of mouse pancreas. The authors hy-
pothesize that other carnitine transporters may be implicated in carnitine transport in
- but not the
-cells.
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