Abstract
The role of endothelin-1 (ET-1) in the development of experimental autoimmune encephalomyelitis (EAE) was studied by the blocking the action of ET-1 with a receptor antagonist, BQ-123. Intrathecal administration of BQ-123 significantly ameliorated EAE progression at the peak stage of EAE (p<0.05). By immunohistochemistry, ED-1-positive macrophages in EAE lesions were identified as major producers of ET-1, whereas the immunoreactivity of ET-1 on brain cells, such as astrocytes, was dramatically increased in accordance with the progression of EAE. This study points to a putative pro-1nflammatory role for ET-1 in the pathogenesis of EAE. One possible application for the ET-1 receptor antagonist might be helpful in the therapy of autoimmune neurological disorders.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antihypertensive Agents / pharmacology*
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Astrocytes / drug effects
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Astrocytes / metabolism
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Astrocytes / pathology
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Blood Vessels / drug effects
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Blood Vessels / pathology
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Blood Vessels / physiopathology
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Demyelinating Diseases / drug therapy
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Demyelinating Diseases / pathology
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Demyelinating Diseases / physiopathology*
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Disease Models, Animal
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Encephalitis / drug therapy
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Encephalitis / pathology
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Encephalitis / physiopathology
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Encephalomyelitis, Autoimmune, Experimental / drug therapy
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Encephalomyelitis, Autoimmune, Experimental / pathology
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Encephalomyelitis, Autoimmune, Experimental / physiopathology*
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Endothelin Receptor Antagonists*
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Endothelin-1 / antagonists & inhibitors*
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Endothelin-1 / metabolism
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Female
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Glial Fibrillary Acidic Protein / metabolism
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Immunohistochemistry
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Injections, Spinal
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Male
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Nerve Degeneration / drug therapy
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Nerve Degeneration / pathology
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Nerve Degeneration / physiopathology
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Peptides, Cyclic / pharmacology*
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Rats
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Rats, Inbred Lew
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Receptors, Endothelin / metabolism
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Spinal Cord / drug effects*
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Spinal Cord / pathology
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Spinal Cord / physiopathology
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Treatment Outcome
Substances
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Antihypertensive Agents
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Endothelin Receptor Antagonists
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Endothelin-1
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Glial Fibrillary Acidic Protein
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Peptides, Cyclic
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Receptors, Endothelin
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cyclo(Trp-Asp-Pro-Val-Leu)