Biomedical Engineering Reference
In-Depth Information
MDR1
OC
+
(hydrophobic)
OC
+
(hydrophobic)
Basolateral Membrane
Na
+
OCTN2
OC
+
Carnitine
H
+
(or OC
+
)
OCT2
OCTN1
OC
+
−
70 mV
H
+
(Carnitine, OC
+
)
OCTN2
OCT1
(rodent)
OC
+
OC
+
H
+
MATE1
OC
+
H
+
MATE2
OC
+
Apical Membrane
PROXIMAL TUBULE EPITHELIAL CELL
(a)
AT P
HEPATOCYTE
Canalicular (Apical)
Membrane
MDR3
OC
+
OC
+
Bile Canaliculus
H
+
−
70 mV
MATE1
MDR1
Sinusoidal (Basolateral)
Membrane
OC
+
AT P
OCT1
OCT1
OC
+
Blood
OC
+
(b)
FIGURE 2.2.
Model of organic cation transport in excretory organs. (
a
) Kidney: In humans,
OCT2 is the primary transporter responsible for uptake of hydrophilic organic cations (OC
+
)
across the basolateral membrane, in a process driven by the inside-negative membrane potential.
In rodents, OCT1 and OCT2 are expressed to a similar degree in kidney. Efflux of organic
cations across the luminal (apical) membrane for excretion occurs by an organic cation-H
+
exchange mechanism, and several transporters are suspected to be involved in apical OC
+
transport. Membrane-permeable organic cations may not require facilitative transport across
the basolateral membrane, and these hydrophobic cations may be substrates for the apical
efflux pump MDR1. (
b
) Liver: OCT1 is by far the most abundant organic cation transporter in
the liver, where it serves as a basolateral, potential-driven uptake transporter. After entry into
the hepatocyte, cationic drugs may be metabolized or excreted into bile via the primary active
efflux transporters MDR1 and MDR3, or via the organic cation-H
+
exchanger MATE1.
Search WWH ::
Custom Search