The Cell - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 33

to move substrates, whereas active transport allows movement against the electro-
chemical gradient but at the expense of ATP. The drug transporters have been classi-
fied into various groups on account of different modes or principles of operation.
Efflux and Influx Transporters
These transporters are categorized based on the direction of movement of material.
Efflux transporters move the substrates from intracellular compartment to extracel-
lular compartment; conversely, the influx transporters allow for movement of sub-
strates from an extracellular site to inside the cell.
Absorptive and Secretory Transporters
Absorptive transporters are those that allow the movement of their substrates into
the blood stream, and those that excrete or secrete material from the blood into gut
lumen, bile, or urine, and so forth, are termed secretory transporters. However, the
transporters in fetus and brain are termed absorptive if they facilitate the flux of sub-
strate into these compartments.
It seems that absorptive and influx transporters are the same, but it may not be
true for every case. In some cases, the transporter may be the influx transporter but
is ultimately for excretion of the substrate, for example, the organic anion transporter
(OAT1).
ATP-Binding Cassette and Solute Carrier Transporters
ATP-binding cassette (ABC) transporters constitute a family of transporters that are
primary active transporters and require hydrolysis of ATP to permit movement of
material. This family includes the multidrug resistance protein (MDR) and the mul-
tidrug resistance-associated protein (MRP). Solute carrier (SLC) transporters utilize
an electrochemical or ion gradient to move the substrates. This is also a large family,
in which most of the drug transporters are classified [10] .
Organic Cation Transporters
The organic cation transporters (OCTs) are a family of cation transporters with spec-
ificity for a large number of cationic substrates that are both endogenous and exog-
enous. There are three types of OCTs—OCT1, OCT2, OCT, all being SLC-type
membrane proteins. The members of the family have structural similarity, similar-
ity in substrate specificity, and similar transport mechanisms. OCT1 are localized
primarily in the liver, where they are involved with the hepatic metabolism/biliary
excretion of substrates. OCT2 are distributed in the kidney and take up the cations
from the renal proximal tubule. OCT has a more wide distribution but higher sub-
strate selectivity for monoamines. There are various genetic isoforms of the trans-
porter leading to differential individual responses. These transporters are often
studied and characterized in knockout mouse models [110,111] .