Biomedical Engineering Reference
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was membrane-potential dependent. Human OCT2 has also been identified.
87
Interest-
ingly, unlike rOct2, hOCT2 was localized to the apical membrane of the distal tubule.
87
A splice variant of hOCT2, OCT2A, has a truncated C-terminus lacking the last three
putative transmembrane domains, transported TEA with about 5% of the wild type's
maximal rate, but revealed higher affinity for several organic catios.
93
The reason for
the species differences observed in the localization of OCT2 in the kidney is not yet
known.
OCT3
OCT3 was isolated from a rat placental cDNA library,
94
and their human and
mouse homologs were identified successively.
95-97
Rodent Oct3 and human OCT3
mRNA was expressed in various tissues, including the kidney.
94
,
97
Rat Oct3 exhibited
an uptake of TEA and guanidine, which was inhibited by MPP
+
. Electrophysiological
studies revealed that rOct3-mediated TEA uptake evoked a potential-dependent
inward current, which was markedly influenced by the extracellular pH. Rat Oct3
interacted with dopamine, the neurotoxins amphetamine and methamphetamine, as
well as a variety of steroids.
98
Although human OCT3 transports diverse organic
cations, including catecholamines,
95
,
96
OCT3 appears to be inhibited selectively by
corticosterone and
o
-methylisoprenaline compared to other OCTs.
99
The localization
and intrarenal distribution of OCT3 is unknown.
OCTN1
Two other members of the OCT family, OCTN1 and OCTN2, have been
cloned based on their homology to OCT. OCTN1 was identified from human fetal
liver.
100
Human OCTN1 (hOCTN1) mRNA was expressed abundantly in the kidney,
trachea, bone marrow, fetal liver, and several human cancer cell lines.
100
When ex-
pressed in HEK293 cells, hOCTN1 mediated the saturable and pH-dependent TEA
uptake. TEA efflux mediated by OCTN1 was also dependent on the acidic external
medium pH.
101
OCTN1 transported several drugs and endogenous compounds, in-
cluding quinidine, verapamil, and carnitine.
101
Furthermore, OCTN1 was inhibited
by various drugs, such as cimetidine, procainamide, pyrilamine, quinine, cephalori-
dine, and verapamil.
101
Very recently, Grundemann et al. demonstrated that the key
substrate of OCTN1 is ergothioneine, a product biosynthesized by fungi and my-
cobacteria. They thus proposed the functional name ETT (ET transporter) instead of
OCTN1.
102
OCTN2
OCTN2 was identified from a human placental trophoblast cell line by ho-
mology search, and their mouse and rat homologs were isolated successively.
103
,
104
OCTN2 mRNA was detected strongly in adult human kidney, trachea, spleen, bone
marrow, skeletal muscle, heart, and placenta.
105
When expressed in HEK293 cells,
hOCTN2 mediated L-carnitine uptake in a sodium-dependent manner, and it also me-
diated the uptake of TEA and guanidine.
105
Mutations in the OCTN2 gene
SLC22A5
have been linked causally to primary systemic carnitine deficiency, an autosomal
recessive disease characterized by low serum and intracellular concentrations of
carnitine.
106-109
Two mutations in OCTN2, P478L and L352R, resulted in a complete
loss of carnitine transport function, but P478L actually had higher organic cation
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