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Targeting uptake transporters such as organic anion transporting polypeptide 1a4 (Oatp1a4) at the blood–brain barrier (BBB) can facilitate central nervous system (CNS) drug delivery. Effective blood-to-brain drug transport via this strategy requires characterization of mechanisms that modulate BBB transporter expression and/or activity. Here, we show that activation of activin receptor-like kinase (ALK)-1 using bone morphogenetic protein (BMP)-9 increases Oatp1a4 protein expression in rat brain microvessels in vivo. These data indicate that targeting ALK1 signaling with BMP-9 modulates BBB Oatp1a4 expression, presenting a unique opportunity to optimize drug delivery and improve pharmacotherapy for CNS diseases.

journal of cerebral blood flow and metabolism

Bone morphogenetic protein-9 increases the functional expression of organic anion transporting polypeptide 1a4 at the blood–brain barrier via the activin receptor-like kinase-1 receptor