ORGANIC ANION–TRANSPORTING POLYPEPTIDES - Drug Transporters: Molecular Characterization and Role in Drug Disposition - page 80

TABLE 5.2. Tissue Expression of Human OATPs

Small Large

Liver Kidney Intestine Intestine Brain Placenta Testes

Transporter
(Refs.) mRNA Protein mRNA Protein mRNA Protein mRNA Protein mRNA Protein mRNA Protein mRNA Protein

OATP1A2
(13, 15,
30, 41,
114)

+ +++++ +++

OATP1B1
(16, 115,
116)

+ +

OATP1B3
(26, 55,
117)

+ + + +

OATP1C1
(9,30)

+ + +

OATP2A1
(118 120) +

+ + + + + + +

−

OATP2B1
(22,27

+ ++ +++ ++++

− 32,

116)

OATP3A1
(116, 121)

+ + +

OATP4A1
(9, 30, 116,
122)

+ + + + + + + +

OATP4C1
(123)

++

OATP5A1
OATP6A1
(106)

++

5.3. EXPRESSION AND REGULATION OF OATPs

5.3.1. Tissue Distribution

Several members of the OATP superfamily, including OATP1A2, OATP2A1,
OATP2B1, OATP3A1, and OATP4A1, are expressed widely among human tissues
(Table 5.2). Others appear to have tissue-specific expression, such as OATP1B1 and
OATP1B3 in liver, OATP4C1 in kidney, and OATP6A1 in testes (Table 5.2). For
some time, mRNA analysis had been the only source of information about OATP
gene expression in certain tissues, but now with the continued development of spe-
cific antibodies, protein localization studies have begun to shed light on the potential
physiological and pharmacological roles for this transporter family. Hence for a tis-
sue such as liver, OATP1B1, OATP1B3, and OATP2B1 are the main members of the
transporter family expressed on the basolateral surface of hepatocytes, 16 , 26 , 27 while
OATP1A2 is localized on the apical membrane of cholangiocytes. 13 The spectrum
of tissues expressing OATP2B1 protein is now quite large and includes liver, 27 small
intestine, 22 brain, 28 placenta, 29 eye, 30 skin, 31 and mammary gland. 32 By contrast, little
is known about the expression (and function) of OATP5A1. Immunohistochemical
analyses have revealed that the polarized expression of many OATPs in epithelial
cells is tissue dependent (Table 5.2). For example, OATP2B1 is expressed on the
apical membrane of enterocytes, whereas basolateral localization is found in hepato-
cytes and syncytiotrophoblasts. The reasons that account for differences in polarized
expression of OATPs in tissues remain unknown.