title: 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.
abstract: 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.
authors.affiliation: 1 Department of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ, USA.
authors.forename: Wazir
authors.initials: W
authors.lastname: Abdullahi
authors.affiliation: 1 Department of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ, USA.
authors.forename: Hrvoje
authors.initials: H
authors.lastname: Brzica
authors.affiliation: 2 Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, AZ, USA.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Ibbotson
authors.affiliation: 1 Department of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ, USA.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Davis
authors.affiliation: 1 Department of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ, USA.
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Ronaldson
mesh_terms: D029404:Activin Receptors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism; D016503:Drug Delivery Systems; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D055427:Growth Differentiation Factor 2 / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D055806:Microvessels / Q000187:drug effects* / Q000378:metabolism; D027361:Organic Anion Transporters / Q000235:genetics*; D010477:Perfusion; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C526764:Acvrl1 protein, rat; D055427:Growth Differentiation Factor 2; C554430:LDN 193189; D027361:Organic Anion Transporters; D011720:Pyrazoles; D011743:Pyrimidines; C503597:Slco1a4 protein, rat; D029404:Activin Receptors
keywords: Basic science; blood–brain barrier; endothelium; pharmacology; vascular biology