Intrathecal administration of endothelin-1 receptor antagonist ameliorates autoimmune encephalomyelitis in Lewis rats.
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.
Shin
T
T
Department of Veterinary Medicine, Cheju National University, Republic of Korea.
Kang
B
B
Tanuma
N
N
Matsumoto
Y
Y
Wie
M
M
Ahn
M
M
Kang
J
J
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001808:Blood Vessels / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D003711:Demyelinating Diseases / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004660:Encephalitis / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D007278:Injections, Spinal; D008297:Male; D009410:Nerve Degeneration / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D010456:Peptides, Cyclic / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D017466:Receptors, Endothelin / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D005904:Glial Fibrillary Acidic Protein; D010456:Peptides, Cyclic; D017466:Receptors, Endothelin; C072247:cyclo(Trp-Asp-Pro-Val-Leu)