title: Interplay between endothelin and erythropoietin in astroglia: the role in protection against hypoxia.
abstract: We show that, under in vitro conditions, the vulnerability of astroglia to hypoxia is reflected by alterations in endothelin (ET)-1 release and capacity of erythropoietin (EPO) to regulate ET-1 levels. Exposure of cells to 24 h hypoxia did not induce changes in ET-1 release, while 48-72 h hypoxia resulted in increase of ET-1 release from astrocytes that could be abolished by EPO. The endothelin receptor type A (ETA) antagonist BQ123 increased extracellular levels of ET-1 in human fetal astroglial cell line (SV-FHAS). The survival and proliferation of rat primary astrocytes, neural precursors, and neurons upon hypoxic conditions were increased upon administration of BQ123. Hypoxic injury and aging affected the interaction between the EPO and ET systems. Under hypoxia EPO decreased ET-1 release from astrocytes, while ETA receptor blockade enhanced the expression of EPO mRNA and EPO receptor in culture-aged rat astroglia. The blockade of ETA receptor can increase the availability of ET-1 to the ETB receptor and can potentiate the neuroprotective effects of EPO. Thus, the new therapeutic use of combined administration of EPO and ETA receptor antagonists during hypoxia-associated neurodegenerative disorders of the central nervous system (CNS) can be suggested.
authors.affiliation: Institute for Transfusion Medicine and Immunohaematology, German Red Cross Blood Donor Service Baden-Württemberg-Hesse gGmbH, Johann-Wolfgang-Goethe-University Hospital, Sandhofstrasse 1, Frankfurt/Main D-60528, Germany. r.schaefer@blutspende.de.
authors.forename: Richard
authors.initials: R
authors.lastname: Schäfer
authors.affiliation: Department of Clinical Pharmacology, Institute of Clinical and Experimental Pharmacology and Toxicology, University Hospital of Tuebingen, Auf der Morgenstelle 8, Tuebingen D-72076, Germany. drlarsmueller@freenet.de.
authors.forename: Lars
authors.initials: L
authors.lastname: Mueller
authors.affiliation: Department of Clinical Pharmacology, Institute of Clinical and Experimental Pharmacology and Toxicology, University Hospital of Tuebingen, Auf der Morgenstelle 8, Tuebingen D-72076, Germany. pharmakologie@gmx.net.
authors.forename: Reinhild
authors.initials: R
authors.lastname: Buecheler
authors.affiliation: Department of Clinical Pharmacology, Institute of Clinical and Experimental Pharmacology and Toxicology, University Hospital of Tuebingen, Auf der Morgenstelle 8, Tuebingen D-72076, Germany. barbara.proksch@uni-tuebingen.de.
authors.forename: Barbara
authors.initials: B
authors.lastname: Proksch
authors.affiliation: Department of Clinical Pharmacology, Institute of Clinical and Experimental Pharmacology and Toxicology, University Hospital of Tuebingen, Auf der Morgenstelle 8, Tuebingen D-72076, Germany. matthias.schwab@ikp-stuttgart.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Schwab
authors.affiliation: Department of Clinical Pharmacology, Institute of Clinical and Experimental Pharmacology and Toxicology, University Hospital of Tuebingen, Auf der Morgenstelle 8, Tuebingen D-72076, Germany. christoph.gleiter@med.uni-tuebingen.de.
authors.forename: Christoph H
authors.initials: CH
authors.lastname: Gleiter
authors.affiliation: Department of Clinical Pharmacology, Institute of Clinical and Experimental Pharmacology and Toxicology, University Hospital of Tuebingen, Auf der Morgenstelle 8, Tuebingen D-72076, Germany. lusine.danielyan@med.uni-tuebingen.de.
authors.forename: Lusine
authors.initials: L
authors.lastname: Danielyan
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015687:Cell Hypoxia; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000378:metabolism*; D004921:Erythropoietin / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D010456:Peptides, Cyclic / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044022:Receptor, Endothelin A / Q000819:agonists / Q000378:metabolism; D017467:Receptors, Erythropoietin / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D019332:Endothelin-1; D010456:Peptides, Cyclic; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D017467:Receptors, Erythropoietin; D004921:Erythropoietin; C072247:cyclo(Trp-Asp-Pro-Val-Leu)