chapter  5
48 Pages


WithCatia Marzolini, Rommel G. Tirona, Richard B. Kim

The translocation of drugs across biological membranes has generally been considered to be predominantly a passive process. However, recent advances relating to the cloning and expression of individual transporters have revealed the presence of a wide variety of transporters capable of drug uptake as well as efflux transport (Table 1) thus providing a mechanistic basis for carrier-mediated transport. Uptake transporters act by facilitating the translocation of drugs into cells. Their driving force is mainly provided by an exchange or cotransport of intracellular and/or extracellular ions (i.e., Naþ, Hþ, or HCO3

), therefore, their activity is dependent on a sustained electrochemical gradient (1). Included within this class of transporters are members of the organic anion transporting polypeptide (OATP) family, organic anion transporter (OAT), organic cation transporter (OCT), novel organic cation transporter (OCTN), and peptide transporter (PepT) family. By contrast, efflux transporters function to export drugs from the intracellular to the extracellular milieu. Efflux carriers are mainly represented by the ATP-binding cassette (ABC) family of transmembrane transporters. Their driving force is provided by the hydrolysis of ATP so that substrates can be pumped against steep concentration gradients (2). Included within this class of transporters are members of the multidrug resistance proteins (MDR), multidrug resistance-related protein (MRP) family, bile salt export

Table 1 Summary of Drug Transporters

Transporter Gene symbol Chromosome Tissues Polarity

Ref. seq./ Gene bank

OATP-A SLCO1A2 12p12 B, K, I AP NM_005075 OATP-B SLCO2B1 11q13 B, L, K, I BL NM_007256 OATP-C SLCO1B1 12q L BL NM_006446 OATP-D SLCO3A1 15q26 Ub nd NM_013272 OATP-E SLCO4A1 20q13.33 Ub nd NM_016354 OATP-F SLCO1C1 12p12.3 B nd NM_017435 OATP-H SLCO4C1 5q21 K BL NM_180991 OATP-I SLCO6A1 5q21 T nd NM_173488 OATP-J SLCO5A1 8q13.2 nd nd NM_030958 OATP8 SLCO1B3 12p12 L BL NM_019844 PGT SLCO2A1 3q21 Ub nd NM_005630

OAT1 SLC22A6 11q13.1-q13.2 K, B BL NM_004790 OAT2 SLC22A7 6p21.2-p21.1 L, K BL NM_006672 OAT3 SLC22A8 11q11.7 K, B BL NM_004254 OAT4 SLC22A11 11q13.1 K, P AP NM_018484

OCT1 SLC22A1 6q26 K, L, B, I BL NM_003057 OCT2 SLC22A2 6q26 K, B, I BL NM_003058 OCT3 SLC22A3 6q27 P, K, B, I nd NM_021977

OCTN1 SLC22A4 5q31.1 K, L AP NM_003059 OCTN2 SLC22A5 5q31 K, L, B, I AP NM_003060

PepT1 SLC15A1 13q33-q34 I, K AP NM_005073 PepT2 SLC15A2 3q21.1 K, B AP NM_021082

MDR1 ABCB1 7q21.1 K, L, B, I, P AP NM_000927 MDR3 ABCB4 7q21.1 L AP NM_000443 BSEP ABCB11 2q24 L AP NM_003742

MRP1 ABCC1 16p13.1 Ub BL NM_004996 MRP2 ABCC2 10q24 K, L, B, I AP NM_000392 MRP3 ABCC3 17q22 L, A, P, K, I BL NM_003786 MRP4 ABCC4 13q32 Ub AP/BL NM_005845 MRP5 ABCC5 3q27 Ub BL NM_005688 MRP6 ABCC6 16p13.1 L, K BL NM_001171 MRP7 ABCC10 6p21.1 K, B nd NM_033450 MRP8 ABCC11 16q12.1 L, K, Lu nd NM_032583 MRP9 ABCC12 16q12.1 L, K, Lu nd NM_033226

BCRP ABCG2 4q22 L, I, P AP NM_004827

pump (BSEP), and the breast cancer resistance protein (BCRP) (Table 1). Transporters, whether they mediate uptake or efflux, tend to be localized to certain key organs such as the intestine (3), liver (4), kidney (5), brain (6), and are therefore critical modulators of drug absorption, tissue distribution, and elimination (Fig. 1A-C).