Expression and Function of Organic Anion Transporting Polypeptides in the Human Brain: Physiological and Pharmacological Implications

The central nervous system (CNS) is an important pharmacological target, but it is very effectively protected by the blood–brain barrier (BBB), thereby impairing the efficacy of many potential active compounds as they are unable to cross this barrier. Among others, membranous efflux transporters lik...

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Published in:Pharmaceutics Vol. 13; no. 6; p. 834
Main Authors: Schäfer, Anima M., Meyer zu Schwabedissen, Henriette E., Grube, Markus
Format: Journal Article
Language:English
Published: Basel MDPI AG 04.06.2021
MDPI
Subjects:
ABC transporters
blood–brain barrier
brain
Drugs
expression
Liver
neurosteroids
OATP
Physiology
Polypeptides
Proteins
Review
substrates
Thyroid gland
ISSN:1999-4923, 1999-4923
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Abstract The central nervous system (CNS) is an important pharmacological target, but it is very effectively protected by the blood–brain barrier (BBB), thereby impairing the efficacy of many potential active compounds as they are unable to cross this barrier. Among others, membranous efflux transporters like P-Glycoprotein are involved in the integrity of this barrier. In addition to these, however, uptake transporters have also been found to selectively uptake certain compounds into the CNS. These transporters are localized in the BBB as well as in neurons or in the choroid plexus. Among them, from a pharmacological point of view, representatives of the organic anion transporting polypeptides (OATPs) are of particular interest, as they mediate the cellular entry of a variety of different pharmaceutical compounds. Thus, OATPs in the BBB potentially offer the possibility of CNS targeting approaches. For these purposes, a profound understanding of the expression and localization of these transporters is crucial. This review therefore summarizes the current state of knowledge of the expression and localization of OATPs in the CNS, gives an overview of their possible physiological role, and outlines their possible pharmacological relevance using selected examples.
AbstractList The central nervous system (CNS) is an important pharmacological target, but it is very effectively protected by the blood–brain barrier (BBB), thereby impairing the efficacy of many potential active compounds as they are unable to cross this barrier. Among others, membranous efflux transporters like P-Glycoprotein are involved in the integrity of this barrier. In addition to these, however, uptake transporters have also been found to selectively uptake certain compounds into the CNS. These transporters are localized in the BBB as well as in neurons or in the choroid plexus. Among them, from a pharmacological point of view, representatives of the organic anion transporting polypeptides (OATPs) are of particular interest, as they mediate the cellular entry of a variety of different pharmaceutical compounds. Thus, OATPs in the BBB potentially offer the possibility of CNS targeting approaches. For these purposes, a profound understanding of the expression and localization of these transporters is crucial. This review therefore summarizes the current state of knowledge of the expression and localization of OATPs in the CNS, gives an overview of their possible physiological role, and outlines their possible pharmacological relevance using selected examples.
The central nervous system (CNS) is an important pharmacological target, but it is very effectively protected by the blood-brain barrier (BBB), thereby impairing the efficacy of many potential active compounds as they are unable to cross this barrier. Among others, membranous efflux transporters like P-Glycoprotein are involved in the integrity of this barrier. In addition to these, however, uptake transporters have also been found to selectively uptake certain compounds into the CNS. These transporters are localized in the BBB as well as in neurons or in the choroid plexus. Among them, from a pharmacological point of view, representatives of the organic anion transporting polypeptides (OATPs) are of particular interest, as they mediate the cellular entry of a variety of different pharmaceutical compounds. Thus, OATPs in the BBB potentially offer the possibility of CNS targeting approaches. For these purposes, a profound understanding of the expression and localization of these transporters is crucial. This review therefore summarizes the current state of knowledge of the expression and localization of OATPs in the CNS, gives an overview of their possible physiological role, and outlines their possible pharmacological relevance using selected examples.The central nervous system (CNS) is an important pharmacological target, but it is very effectively protected by the blood-brain barrier (BBB), thereby impairing the efficacy of many potential active compounds as they are unable to cross this barrier. Among others, membranous efflux transporters like P-Glycoprotein are involved in the integrity of this barrier. In addition to these, however, uptake transporters have also been found to selectively uptake certain compounds into the CNS. These transporters are localized in the BBB as well as in neurons or in the choroid plexus. Among them, from a pharmacological point of view, representatives of the organic anion transporting polypeptides (OATPs) are of particular interest, as they mediate the cellular entry of a variety of different pharmaceutical compounds. Thus, OATPs in the BBB potentially offer the possibility of CNS targeting approaches. For these purposes, a profound understanding of the expression and localization of these transporters is crucial. This review therefore summarizes the current state of knowledge of the expression and localization of OATPs in the CNS, gives an overview of their possible physiological role, and outlines their possible pharmacological relevance using selected examples.
Author Schäfer, Anima M.
Grube, Markus
Meyer zu Schwabedissen, Henriette E.
AuthorAffiliation 1 Biopharmacy, Department Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland; anima.schaefer@unibas.ch (A.M.S.); h.meyerzuschwabedissen@unibas.ch (H.E.M.z.S.)
2 Center of Drug Absorption and Transport (C_DAT), Department of Pharmacology, University Medicine of Greifswald, 17489 Greifswald, Germany
AuthorAffiliation_xml – name: 1 Biopharmacy, Department Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland; anima.schaefer@unibas.ch (A.M.S.); h.meyerzuschwabedissen@unibas.ch (H.E.M.z.S.)
– name: 2 Center of Drug Absorption and Transport (C_DAT), Department of Pharmacology, University Medicine of Greifswald, 17489 Greifswald, Germany
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SecondaryResourceType review_article
Snippet The central nervous system (CNS) is an important pharmacological target, but it is very effectively protected by the blood–brain barrier (BBB), thereby...
The central nervous system (CNS) is an important pharmacological target, but it is very effectively protected by the blood-brain barrier (BBB), thereby...
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StartPage 834
SubjectTerms ABC transporters
blood–brain barrier
brain
Drugs
expression
Liver
neurosteroids
OATP
Physiology
Polypeptides
Proteins
Review
substrates
Thyroid gland
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Title Expression and Function of Organic Anion Transporting Polypeptides in the Human Brain: Physiological and Pharmacological Implications
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Volume 13
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