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Cited by 100Drug Transport and Resistance MechanismsBarrier Structure and Function StudiesNeuropeptides and Animal Physiology

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Differential cellular expression of organic anion transporting peptides OATP1A2 and OATP2B1 in the human retina and brain: implications for carrier-mediated transport of neuropeptides and neurosteriods in the CNS

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Gao, Bo, Vavricka, Stephan R., Meier, Peter J., Stieger, Bruno·2015·Pflügers Archiv - European Journal of Physiology
DOI 10.1007/s00424-014-1596-x
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Abstract

Organic anion transporting polypeptides (OATPs) are polyspecific organic anion transporters, which are expressed in the blood-brain barrier, the choroid plexus, and other organs. The physiologic function of OATPs in extrahepatic tissues remains ambiguous. In rat retina, members of the OATP family are expressed. We therefore investigated the human retina for the expression of OATP1A2 and OATP2B1 and extended the study to human brain. Furthermore, we searched for peptide neurotransmitters as novel OATP substrates. OATP1A2 displayed a broad expression pattern in human retina as assessed by immunofluorescence localization. It is expressed in photoreceptor bodies and somas of amacrine cells. OATP1B2 expression is restricted to the inner nuclear layer and to the inner plexiform layer. Using paraffin sections from human cortex, cerebellum, and hippocampus, OATP1A2 was localized to neurons and neuronal processes, while OATP2B1 is expressed in endothelial cells of brain capillaries. Substance P and vasoactive intestinal peptide were identified as substrates for OATP1A2 and OATP2B1. Double-labeling immunofluorescence of human retina demonstrated the presence of substance P and of vasoactive intestinal peptides in neurons expressing OATP1A2 and OATP2B1, respectively. The expression of OATP1A2 and OATP2B1 in retinal neurons implies a role of these transporters in the reuptake of peptide neurotransmitters released from retinal neurons. The abundant expression of OATP1A2 in brain neurons points to the possibility that OATP1A2 could be involved in the homeostasis of neurosteroids. The high expression of OATP2B1 in brain capillaries supports an important function of OATPs in substance penetration across the blood-brain barrier.

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Metadata

Authors
Gao, B., Vavricka, S. R., Meier, P. J., & Stieger, B.
Affiliations
  • University Hospital Zurich (CH)
  • University of Basel (CH)
Corresponding author
Stieger, Bruno
ORCID
Venue
Pflügers Archiv - European Journal of Physiology
Publisher
Springer Science and Business Media LLC
Published
2014-08-19
Volume
467
Issue
7
Pages
1481-1493
ISSN
  • 0031-6768 (ISSN-L)
  • 1432-2013
DOI
10.1007/s00424-014-1596-x
OpenAlex
W2095577431
Cited by
100
References
0
Citations by year
2026: 7 · 2025: 11 · 2024: 10 · 2023: 5 · 2022: 8 · 2021: 9 · 2020: 6 · 2019: 10 · 2018: 13 · 2017: 8 · 2016: 6 · 2015: 7
FWCI
3.37
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Pflügers Archiv - European Journal of Physiology (publishedVersion)
  • PubMed (publishedVersion)
  • RERO DOC (Universität Bern) (submittedVersion)
  • Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
  • Zurich Open Repository and Archive (University of Zurich)
Funders
  • National Science Foundation
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (144195)
Topics
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Keywords
organic anion transporting polypeptides, OATP1A2, OATP2B1, retina, brain, blood-brain barrier, substance P, vasoactive intestinal peptide, choroid plexus, photoreceptors, amacrine cells, brain microvascular endothelial cells, carrier-mediated transport
MeSH terms
Adult, Aged, Aged, 80 and over, Animals, Biological Transport, Active, Brain, Female, Humans, Male, Middle Aged, Organ Specificity, Retina, RNA, Messenger, Substance P, Vasoactive Intestinal Peptide, Xenopus, Organic Anion Transporters

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