PMC:2678986 / 18858-20233 JSONTXT

{"project":"2_test","denotations":[{"id":"19176219-16078135-99578315","span":{"begin":216,"end":220},"obj":"16078135"},{"id":"19176219-16078135-99578315","span":{"begin":216,"end":220},"obj":"16078135"},{"id":"19176219-15528451-99578316","span":{"begin":238,"end":242},"obj":"15528451"},{"id":"19176219-15528451-99578316","span":{"begin":238,"end":242},"obj":"15528451"},{"id":"19176219-18535159-99578319","span":{"begin":286,"end":290},"obj":"18535159"},{"id":"19176219-18535159-99578319","span":{"begin":286,"end":290},"obj":"18535159"},{"id":"19176219-17172311-99578320","span":{"begin":640,"end":644},"obj":"17172311"},{"id":"19176219-17172311-99578320","span":{"begin":640,"end":644},"obj":"17172311"},{"id":"19176219-10470083-99578321","span":{"begin":773,"end":777},"obj":"10470083"},{"id":"19176219-10470083-99578321","span":{"begin":773,"end":777},"obj":"10470083"},{"id":"19176219-10840050-99578322","span":{"begin":797,"end":801},"obj":"10840050"},{"id":"19176219-10840050-99578322","span":{"begin":797,"end":801},"obj":"10840050"},{"id":"19176219-18535159-99578323","span":{"begin":931,"end":935},"obj":"18535159"},{"id":"19176219-18535159-99578323","span":{"begin":931,"end":935},"obj":"18535159"},{"id":"19176219-10470083-99578324","span":{"begin":1093,"end":1097},"obj":"10470083"},{"id":"19176219-10470083-99578324","span":{"begin":1093,"end":1097},"obj":"10470083"},{"id":"19176219-15167283-99578325","span":{"begin":1298,"end":1302},"obj":"15167283"},{"id":"19176219-15167283-99578325","span":{"begin":1298,"end":1302},"obj":"15167283"},{"id":"19176219-12134229-99578326","span":{"begin":1369,"end":1373},"obj":"12134229"},{"id":"19176219-12134229-99578326","span":{"begin":1369,"end":1373},"obj":"12134229"},{"id":"19176219-16078135-3576957","span":{"begin":286,"end":290},"obj":"16078135"},{"id":"19176219-16078135-3576957","span":{"begin":286,"end":290},"obj":"16078135"},{"id":"19176219-15528451-3576957","span":{"begin":286,"end":290},"obj":"15528451"},{"id":"19176219-15528451-3576957","span":{"begin":286,"end":290},"obj":"15528451"},{"id":"19176219-16284458-3576957","span":{"begin":286,"end":290},"obj":"16284458"},{"id":"19176219-16284458-3576957","span":{"begin":286,"end":290},"obj":"16284458"},{"id":"19176219-17890284-3576957","span":{"begin":286,"end":290},"obj":"17890284"},{"id":"19176219-17890284-3576957","span":{"begin":286,"end":290},"obj":"17890284"},{"id":"19176219-18535159-3576957","span":{"begin":286,"end":290},"obj":"18535159"},{"id":"19176219-18535159-3576957","span":{"begin":286,"end":290},"obj":"18535159"},{"id":"19176219-17172311-3576958","span":{"begin":640,"end":644},"obj":"17172311"},{"id":"19176219-17172311-3576958","span":{"begin":640,"end":644},"obj":"17172311"},{"id":"19176219-10470083-3576959","span":{"begin":797,"end":801},"obj":"10470083"},{"id":"19176219-10470083-3576959","span":{"begin":797,"end":801},"obj":"10470083"},{"id":"19176219-10840050-3576959","span":{"begin":797,"end":801},"obj":"10840050"},{"id":"19176219-10840050-3576959","span":{"begin":797,"end":801},"obj":"10840050"},{"id":"19176219-18535159-3576960","span":{"begin":931,"end":935},"obj":"18535159"},{"id":"19176219-18535159-3576960","span":{"begin":931,"end":935},"obj":"18535159"},{"id":"19176219-10470083-3576961","span":{"begin":1093,"end":1097},"obj":"10470083"},{"id":"19176219-10470083-3576961","span":{"begin":1093,"end":1097},"obj":"10470083"},{"id":"19176219-15167283-3576962","span":{"begin":1298,"end":1302},"obj":"15167283"},{"id":"19176219-15167283-3576962","span":{"begin":1298,"end":1302},"obj":"15167283"},{"id":"19176219-12134229-3576963","span":{"begin":1369,"end":1373},"obj":"12134229"},{"id":"19176219-12134229-3576963","span":{"begin":1369,"end":1373},"obj":"12134229"}],"text":"The HIV PIs saquinavir, ritonavir and lopanivir were found to be substrates of MRP-1 and MRP-2 and therefore these transporters may also contribute to the limited penetration of PIs into the brain (Bachmeier et al., 2005; Park and Sinko, 2005; Janneh et al., 2005, 2007; Eilers et al., 2008). A recent in vitro study demonstrated that MRP-1, MRP-2 and MRP-3 were also inhibited in a concentration-dependent manner by NNRTIs (delavirdine, efavirenz and nevirapine), NRTI (abacavir, emtricitabine and lamivudine) and the NtRTI, tenofovir. This inhibition was particularly apparent for delaviridine, efavirenz and emtricitabine (Weiss et al., 2007). In addition, MRP-4 and MRP-5 are thought to be low-affinity transporters of nucleoside-based antiretrovirals (Schuetz et al., 1999; Wijnholds et al., 2000) and both have been implicated in the rapid removal of zidovudine from human brain microvessel endothelial cells (Eilers et al., 2008). Previous studies have also suggested an association between MRP-4 over-expression and increased efflux of nucleoside-based anti-HIV drugs (Schuetz et al., 1999). A previous in vitro study revealed that ritonavir induces the expression of MRP-1 in a concentration-dependent manner, however this was noted in human colon in adenocarcinoma cells (Gimenez et al., 2004). MRP-1 is also thought to promote HIV replication (Speck et al., 2002)."}