Arizona Health Sciences

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.

TitleBone 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.
Publication TypeJournal Article
Year of Publication2017
AuthorsAbdullahi W, Brzica H, Ibbotson K, Davis TP, Ronaldson PT
JournalJ Cereb Blood Flow Metab
Volume37
Issue7
Pagination2340-2345
Date Published2017 Jul
ISSN1559-7016
KeywordsActivin Receptors, Animals, Biological Transport, Blood-Brain Barrier, Drug Delivery Systems, Female, Gene Expression Regulation, Growth Differentiation Factor 2, Microvessels, Organic Anion Transporters, Perfusion, Pyrazoles, Pyrimidines, Rats, Sprague-Dawley, Signal Transduction
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.

DOI10.1177/0271678X17702916
Alternate JournalJ. Cereb. Blood Flow Metab.
PubMed ID28387157
PubMed Central IDPMC5531361
Faculty Member Reference: 
Thomas P Davis, PhD
Patrick T Ronaldson, PhD