Four different types of protease-activated receptors are widely expressed in the brain and are up-regulated in hippocampus by severe ischemia

Authors

  • Frank Striggow,

    1. 1 Institute for Neurobiochemistry, Otto-von-Guericke-University Magdeburg, Medical School, Leipziger Strasse 44, D-39120 Magdeburg, Germany 2 Project Group Neuropharmacology, Leibniz-Institute for Neurobiology, POB 1860, D-39118 Magdeburg, Germany 3 Institute of Applied Neurosciences, Leipziger Strasse 44, D-39120 Magdeburg, Germany 4 Institute of Pharmacology and Toxicology, Otto-von-Guericke-University, Magdeburg, Germany
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  • 1 Monika Riek-Burchardt,

    1. 1 Institute for Neurobiochemistry, Otto-von-Guericke-University Magdeburg, Medical School, Leipziger Strasse 44, D-39120 Magdeburg, Germany 2 Project Group Neuropharmacology, Leibniz-Institute for Neurobiology, POB 1860, D-39118 Magdeburg, Germany 3 Institute of Applied Neurosciences, Leipziger Strasse 44, D-39120 Magdeburg, Germany 4 Institute of Pharmacology and Toxicology, Otto-von-Guericke-University, Magdeburg, Germany
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  • 2 Annett Kiesel,

    1. 1 Institute for Neurobiochemistry, Otto-von-Guericke-University Magdeburg, Medical School, Leipziger Strasse 44, D-39120 Magdeburg, Germany 2 Project Group Neuropharmacology, Leibniz-Institute for Neurobiology, POB 1860, D-39118 Magdeburg, Germany 3 Institute of Applied Neurosciences, Leipziger Strasse 44, D-39120 Magdeburg, Germany 4 Institute of Pharmacology and Toxicology, Otto-von-Guericke-University, Magdeburg, Germany
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  • 1 Werner Schmidt,

    1. 1 Institute for Neurobiochemistry, Otto-von-Guericke-University Magdeburg, Medical School, Leipziger Strasse 44, D-39120 Magdeburg, Germany 2 Project Group Neuropharmacology, Leibniz-Institute for Neurobiology, POB 1860, D-39118 Magdeburg, Germany 3 Institute of Applied Neurosciences, Leipziger Strasse 44, D-39120 Magdeburg, Germany 4 Institute of Pharmacology and Toxicology, Otto-von-Guericke-University, Magdeburg, Germany
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  • 3 Petra Henrich-Noack,

    1. 1 Institute for Neurobiochemistry, Otto-von-Guericke-University Magdeburg, Medical School, Leipziger Strasse 44, D-39120 Magdeburg, Germany 2 Project Group Neuropharmacology, Leibniz-Institute for Neurobiology, POB 1860, D-39118 Magdeburg, Germany 3 Institute of Applied Neurosciences, Leipziger Strasse 44, D-39120 Magdeburg, Germany 4 Institute of Pharmacology and Toxicology, Otto-von-Guericke-University, Magdeburg, Germany
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  • 3 Jörg Breder,

    1. 1 Institute for Neurobiochemistry, Otto-von-Guericke-University Magdeburg, Medical School, Leipziger Strasse 44, D-39120 Magdeburg, Germany 2 Project Group Neuropharmacology, Leibniz-Institute for Neurobiology, POB 1860, D-39118 Magdeburg, Germany 3 Institute of Applied Neurosciences, Leipziger Strasse 44, D-39120 Magdeburg, Germany 4 Institute of Pharmacology and Toxicology, Otto-von-Guericke-University, Magdeburg, Germany
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  • 3 Manfred Krug,

    1. 1 Institute for Neurobiochemistry, Otto-von-Guericke-University Magdeburg, Medical School, Leipziger Strasse 44, D-39120 Magdeburg, Germany 2 Project Group Neuropharmacology, Leibniz-Institute for Neurobiology, POB 1860, D-39118 Magdeburg, Germany 3 Institute of Applied Neurosciences, Leipziger Strasse 44, D-39120 Magdeburg, Germany 4 Institute of Pharmacology and Toxicology, Otto-von-Guericke-University, Magdeburg, Germany
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  • 4 Klaus G. Reymann,

    1. 1 Institute for Neurobiochemistry, Otto-von-Guericke-University Magdeburg, Medical School, Leipziger Strasse 44, D-39120 Magdeburg, Germany 2 Project Group Neuropharmacology, Leibniz-Institute for Neurobiology, POB 1860, D-39118 Magdeburg, Germany 3 Institute of Applied Neurosciences, Leipziger Strasse 44, D-39120 Magdeburg, Germany 4 Institute of Pharmacology and Toxicology, Otto-von-Guericke-University, Magdeburg, Germany
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  • and 2,3 Georg Reiser 1

    1. 1 Institute for Neurobiochemistry, Otto-von-Guericke-University Magdeburg, Medical School, Leipziger Strasse 44, D-39120 Magdeburg, Germany 2 Project Group Neuropharmacology, Leibniz-Institute for Neurobiology, POB 1860, D-39118 Magdeburg, Germany 3 Institute of Applied Neurosciences, Leipziger Strasse 44, D-39120 Magdeburg, Germany 4 Institute of Pharmacology and Toxicology, Otto-von-Guericke-University, Magdeburg, Germany
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: Professor Dr Georg Reiser, as above.
E-mail: georg.reiser@medizin.uni-magdeburg.de

Abstract

A variety of extracellular serine proteases are expressed in the central nervous system or might permeate the blood–brain barrier under pathological conditions. However, their intracerebral targets and physiological functions are largely unknown. Here, we show that four distinct subtypes of protease-activated receptors (PARs) are abundantly expressed in the adult rat brain and in organotypic hippocampal slice cultures. PAR-1 expression was significant in the hippocampus, cortex and amygdala. Highest densities of PAR-2 and PAR-3 were observed in hippocampus, cortex, amygdala, thalamus, hypothalamus and striatum. Apart from the striatum, a similar localization was found for PAR-4. Within the hippocampal formation, each PAR subtype was predominantly localized in the pyramidal cell layers. Additionally, we identified PAR-2 in mossy fibers between dentate gyrus and CA3, PAR-3 in the subiculum and PAR-4 in CA3 and in mossy fibres as well as in the stratum lacunosum moleculare. After exposing hippocampal slice cultures to a severe experimental ischemia (oxygen–glucose deprivation), the expression of PARs 1–3 was up-regulated with subtype-specific kinetics. The localization of PARs in brain regions particularly vulnerable to ischemic insults as well as distinct alterations in the expression pattern after experimental ischemia support the notion of an important role of extracellular serine proteases and PARs in cerebral ischemia.

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