Table 3.

Main effects of the reference protein kinase C (PKC) activator phorbol-12-myristate-13-acetate (PMA) on drug transporter activity, localization and/or expression. P-gp: P-glycoprotein; BSEP: bile salt export pump; MRP: multidrug resistance-associated protein; BCRP: breast cancer resistance protein; OATP: organic anion transporting polypeptide; OAT: organic anion transporter; NTCP: sodium-taurocholate co-transporting polypeptide; OCT: organic cation transporter; OCTN: organic cation transporter novel; ENT: equilibrative nucleoside transporter; PEPT: peptide transporter.

Transporter	Activity	Localization	Expression
P-gp	Increase (human cancer cell lines, mouse renal proximal tubules) [13,59,60,61]		Increase (human cancer cells and primary human hepatocytes) [17,62,63]
BSEP		Internalization (rat liver) [64]	Decrease (primary human hepatocytes) [18]
MRP2		Internalization (human hepatic HepG2 cell line) [65]	No change (primary human hepatocytes) [18]
MRP3			Increase (primary human hepatocytes) [18]
BCRP			No change (primary human hepatocytes) [18]
OATP1A2		Internalization (OATP1A2- COS-7 cells) [66]
OATP1B1		Internalization (OATP1B1-HEK293 cells) [67]	Decrease (primary human hepatocytes) [18]
OATP1B3	Decrease (primary human hepatocytes) [14]		Decrease (primary human hepatocytes) [18]
OATP2B1		Internalization (OATP2B1-MDCKII cells, Caco-2 cell line, human placenta, human hepatic HepaRG cell line) [68], (Figure 2a)	Decrease (primary human hepatocytes) [18]
OAT1		Internalization (OAT1-COS-7 cells) [69]
OAT3	Decrease (rabbit renal proximal tubules) [70]
NTCP		Internalization (primary rat hepatocytes, NTCP-HepG2 cells) [64,71]	Decrease (primary human hepatocytes) [18]
OCT1		No change (Figure 2b)	Decrease (primary human hepatocytes) [18]
OCTN2		Increase in membrane expression (rat astrocytes) [72]
ENT1	Increase (ENT1-PK15-NTD cells) [73]	Increase in membrane expression (ENT1- PK15-NTD cells) [73]
PEPT1	Decrease (human intestinal Caco-2 cell line) [74]
PEPT2	Decrease (porcine kidney LLC-PK1 cell line) [75]