4.2.3  OCTs
The literature concerning OCT expression in the brain is at times contradictory, and this maybe the result of variation between species and also differing area and levels of expression of the transporters within the brain (Sweet et al., 2001). A study by Slitt et al. (2002) found that mRNA for all five organic cation transporters could be detected in the rat brain. Although this work did not evaluate whether the transporters were present at the brain barriers, additional studies have provided some evidence for the presence for individual organic cation transporters at the BBB and choroid plexus. It has been established that OCTN2 is found on the luminal face (and possibly the abluminal face too) of the cerebral capillary endothelial cells of humans, rats, pigs and cows (Kido et al., 2001). OCT2, OCT3, OCTN1 and OCTN2 (but not OCT1) are also expressed in the rat choroid plexus (Sweet et al., 2001). Human OCTs play a crucial role in the initial step involved in hepatic or renal excretion of many cationic compounds. Furthermore, previous studies have demonstrated the involvement of rat OCTs and an undefined organic cation-proton exchanger in the cellular uptake of AZT and 3TC, raising the possibility that human OCTs could also be involved in the uptake of anti-HIV drugs (Minuesa et al., 2008). Moreover, Minuesa et al. (2008) revealed that hOCTs were heterogeneously expressed in primary lymphocytes, monocytes, macrophages and dendritic cells. These transporters were also upregulated upon lymphocyte activation.
A recent study suggested that the PIs, nelfinavir, ritonavir, saquinavir and indinavir are possibly inhibitors of OCT1 and OCT2 (Jung et al., 2008). This supported evidence provided by Zhang et al. (2000) that some HIV PIs may be potent inhibitors of cationic drug uptake, but poor substrates for human OCT1 (Zhang et al., 2000). Furthermore, the NRTIs, lamivudine and zalcitabine are substrates of OCT1 and OCT2 (Jung et al., 2008). Moreover, when assessing the expression of OCTs in lymph nodes of HIV-infected patients in comparison to healthy controls, Jung and colleagues found that OCT1 and OCT2 were upregulated in the lymph nodes of HIV-infected patients, indicating that the accumulation of OCT substrates would be much higher in the lymph nodes of these patients. This could be due to the activation of the immune system and effects of cytokines induced by HIV infection (Jung et al., 2008). This study implies that a sound knowledge of OCTs is crucial in understanding both drug interactions that may occur with HAART and also the role they play in regulating drug transport.