PMC:2678986 / 15592-16576 JSONTXT

{"project":"2_test","denotations":[{"id":"19176219-16278373-99578300","span":{"begin":317,"end":321},"obj":"16278373"},{"id":"19176219-16278373-99578300","span":{"begin":317,"end":321},"obj":"16278373"},{"id":"19176219-17132686-99578301","span":{"begin":755,"end":759},"obj":"17132686"},{"id":"19176219-17132686-99578301","span":{"begin":755,"end":759},"obj":"17132686"},{"id":"19176219-17697052-99578302","span":{"begin":978,"end":982},"obj":"17697052"},{"id":"19176219-17697052-99578302","span":{"begin":978,"end":982},"obj":"17697052"},{"id":"19176219-16278373-3576946","span":{"begin":317,"end":321},"obj":"16278373"},{"id":"19176219-16278373-3576946","span":{"begin":317,"end":321},"obj":"16278373"},{"id":"19176219-17132686-3576947","span":{"begin":755,"end":759},"obj":"17132686"},{"id":"19176219-17132686-3576947","span":{"begin":755,"end":759},"obj":"17132686"},{"id":"19176219-17697052-3576948","span":{"begin":978,"end":982},"obj":"17697052"},{"id":"19176219-17697052-3576948","span":{"begin":978,"end":982},"obj":"17697052"}],"text":"The proposed mechanism suggested that short-term exposure to the cytokine caused TNF receptor 1 stimulation resulting in ET-1 release and consequent ETB receptor, nitric oxide synthase and protein kinase C activation. This pathway was thought to be activated by LPS to reduce P-gp transporter activity (Hartz et al., 2006). More recently, the same research group found that this initial rapid decrease in transport preceded a 2–3-h plateau at this reduced level of transporter activity, and was then followed by a rapid increase in both transporter activity and protein expression. Collectively, these findings demonstrate that chronic inflammation can tighten the BBB to CNS drugs which are P-gp substrates by upregulating P-gp expression (Bauer et al., 2007). An upregulation of P-gp in rat brain endothelium was also observed in an inflammatory pain model causing a decrease in the penetration of the P-gp substrate, morphine and consequent antinociception (Seelbach et al., 2007)."}