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The ABC of the blood-brain barrier - regulation of drug efflux pumps. 2011

Anne Mahringer, and Melanie Ott, and Isolde Reimold, and Valeska Reichel, and Gert Fricker
Institute of Pharmacy and Molecular Biotechnology, Ruprecht-Karls-University, 69210 Heidelberg, Germany.

According to the World Health Organization Central nervous system disorders are the major medical challenge of the 21st Century, yet treatments for many CNS disorders are either inadequate or absent. One reason is the existence of the blood-brain barrier, which strictly limits the access of substances to the brain. A key element of the barrier function is the expression of ABC export proteins in the luminal membrane of brain microvessel endothelial cells. Understanding the signaling cascades and the response to endogenous and exogenous stimuli, which lead to altered expression or function of the transporters as well as subsequent modulation of the transporters, may offer novel strategies to overcome the barrier and to improve drug delivery to the brain. This review gives a short overview about structure of the key elements of the blood-brain barrier with emphasis on ABC transporters. An insight into regulation of function and expression of these transport proteins is given and the involvement of these transporters in CNS diseases is discussed.

UI MeSH Term Description Entries
D001812 Blood-Brain Barrier Specialized non-fenestrated tightly-joined ENDOTHELIAL CELLS with TIGHT JUNCTIONS that form a transport barrier for certain substances between the cerebral capillaries and the BRAIN tissue. Brain-Blood Barrier,Hemato-Encephalic Barrier,Barrier, Blood-Brain,Barrier, Brain-Blood,Barrier, Hemato-Encephalic,Barriers, Blood-Brain,Barriers, Brain-Blood,Barriers, Hemato-Encephalic,Blood Brain Barrier,Blood-Brain Barriers,Brain Blood Barrier,Brain-Blood Barriers,Hemato Encephalic Barrier,Hemato-Encephalic Barriers
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D002491 Central Nervous System Agents A class of drugs producing both physiological and psychological effects through a variety of mechanisms. They can be divided into "specific" agents, e.g., affecting an identifiable molecular mechanism unique to target cells bearing receptors for that agent, and "nonspecific" agents, those producing effects on different target cells and acting by diverse molecular mechanisms. Those with nonspecific mechanisms are generally further classed according to whether they produce behavioral depression or stimulation. Those with specific mechanisms are classed by locus of action or specific therapeutic use. (From Gilman AG, et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p252) Central Nervous System Drugs
D002493 Central Nervous System Diseases Diseases of any component of the brain (including the cerebral hemispheres, diencephalon, brain stem, and cerebellum) or the spinal cord. CNS Disease,Central Nervous System Disease,Central Nervous System Disorder,CNS Diseases,Central Nervous System Disorders
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001692 Biological Transport The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments. Transport, Biological,Biologic Transport,Transport, Biologic
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D016503 Drug Delivery Systems Systems for the delivery of drugs to target sites of pharmacological actions. Technologies employed include those concerning drug preparation, route of administration, site targeting, metabolism, and toxicity. Drug Targeting,Delivery System, Drug,Delivery Systems, Drug,Drug Delivery System,Drug Targetings,System, Drug Delivery,Systems, Drug Delivery,Targeting, Drug,Targetings, Drug
D042783 Endothelial Cells Highly specialized EPITHELIAL CELLS that line the HEART; BLOOD VESSELS; and lymph vessels, forming the ENDOTHELIUM. They are polygonal in shape and joined together by TIGHT JUNCTIONS. The tight junctions allow for variable permeability to specific macromolecules that are transported across the endothelial layer. Capillary Endothelial Cells,Lymphatic Endothelial Cells,Vascular Endothelial Cells,Capillary Endothelial Cell,Cell, Capillary Endothelial,Cell, Endothelial,Cell, Lymphatic Endothelial,Cell, Vascular Endothelial,Cells, Capillary Endothelial,Cells, Endothelial,Cells, Lymphatic Endothelial,Cells, Vascular Endothelial,Endothelial Cell,Endothelial Cell, Capillary,Endothelial Cell, Lymphatic,Endothelial Cell, Vascular,Endothelial Cells, Capillary,Endothelial Cells, Lymphatic,Endothelial Cells, Vascular,Lymphatic Endothelial Cell,Vascular Endothelial Cell

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