In vitro and in vivo study of dolichyl phosphate on the efflux activity of P-glycoprotein at the blood–brain barrier

It has been commonly recognized that accumulated amyloid‐β (Aβ) in the brain plays a crucial role in the pathogenesis of Alzheimer's disease (AD). Since the deficiency of the P‐glycoprotein (P‐gp) at the blood–brain barrier (BBB) in AD may aggravate Aβ deposition and the P‐gp reversal agents display lower selectivity of the action, to selectively restore activity of the efflux pump is eagerly required. This study was designed to investigate the influence of dolichyl‐phosphate (dolichyl‐P) on the P‐gp at the BBB. The results revealed that treatment with dolichyl‐P increased transendothelial transfer of Rhodamine123 (Rh123) and Aβ42 from the apical compartment to the basolateral compartment but reduced that from the basolateral compartment to the apical compartment in the co‐culture of rat brain microvessel endothelial cells (rBMECs) and astrocytes, down regulated P‐gp expression in rBMECs and significantly elevated content of Rh123 in rat cortex and hippocampus tissues. The present results implied that accumulated dolichyl‐P in the brain may exert an important role in the depression of the P‐gp at the BBB, which may suggest valuable clues to promote function of the pump at the BBB in AD.

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