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

Wazir Abdullahi, Hrvoje Brzica, Kathryn Ibbotson, Thomas P Davis, Patrick T Ronaldson

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2340-2345
Number of pages6
JournalJournal of Cerebral Blood Flow and Metabolism
Volume37
Issue number7
DOIs
StatePublished - Jul 1 2017

Fingerprint

Growth Differentiation Factor 2
Activin Receptors
Anions
Peptides
Central Nervous System Agents
Central Nervous System Diseases
Brain
Microvessels
Pharmaceutical Preparations
Drug Therapy
Proteins

Keywords

  • Basic science
  • blood–brain barrier
  • endothelium
  • pharmacology
  • vascular biology

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Cite this

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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.",
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AU - Abdullahi, Wazir

AU - Brzica, Hrvoje

AU - Ibbotson, Kathryn

AU - Davis, Thomas P

AU - Ronaldson, Patrick T

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AB - 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.

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