BQ788, an endothelin ET(B) receptor antagonist, attenuates stab wound injury-induced reactive astrocytes in rat brain.
Endothelins (ETs) are suggested to be involved in pathological or pathophysiological responses on brain injuries. In the present study, an involvement of ETs on activation of astrocytes in vivo was examined by using selective endothelin receptor antagonists. A stab wound injury on rat cerebral cortex increased immunoreactive ET-1 at the injured site. GFAP-positive [GFAP(+)] and vimentin-positive [Vim(+)] cells appeared at the injured site in 1 day to 2 weeks after the injury. A continuous infusion of BQ788, a selective ETB receptor antagonist, into cerebral ventricle (23 nmole/day) attenuated increase in the numbers of GFAP(+) and Vim(+) cells after the injury. FR139317, a selective ETA antagonist (23 nmole/day), slightly decreased the number of Vim(+) cells but not that of GFAP(+) cells. Increase in the number of microglia/macrophages by a stab wound injury, which was determined by Griffonia simplicifolia isolectin B4 staining, was not affected by BQ788 and FR139317. These results suggest that activation of glial ETB receptors is one of the signal cascades leading to reactive astrocytes on brain injuries.
Koyama
Y
Y
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Osaka University, Yamada-Oka, Suita, Japan.
Takemura
M
M
Fujiki
K
K
Ishikawa
N
N
Shigenaga
Y
Y
Baba
A
A
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D001381:Azepines / Q000494:pharmacology; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology*; D002540:Cerebral Cortex / Q000473:pathology; D065128:Endothelin Receptor Antagonists; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology; D008297:Male; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D009842:Oligopeptides / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044023:Receptor, Endothelin B; D014746:Vimentin / Q000378:metabolism; D014951:Wounds, Stab / Q000378:metabolism / Q000473:pathology*
D001381:Azepines; D065128:Endothelin Receptor Antagonists; D005904:Glial Fibrillary Acidic Protein; D007211:Indoles; D009842:Oligopeptides; D010880:Piperidines; D044023:Receptor, Endothelin B; D014746:Vimentin; C079574:FR 139317; C086539:BQ 788