Expression of Endothelin-B Receptors by Gliain VivoIs Increased after CNS Injury in Rats, Rabbits, and Humans

Abstract

Previous studies have demonstrated that neonatal cultures of astrocytes express functional endothelin (ET) receptors. To determine if similar ET receptors are expressed by adult glia we used125I-ET-1 to examine the expression of ET receptors bothin vivoin the normal and transected optic nerves of the rabbit and rat andin vitroin cultures of astrocytes, microglia, or oligodendrocytes. Additionally, we examined the expression of ET receptors in the human optic nerve. Moderate levels of ETBreceptors were identified in the rabbit and rat forebrain, whereas in the normal rabbit, rat, and human optic nerves a low density of ETBreceptors was observed, mainly in association with glial fibrillary acidic protein + (GFAP+) astrocytes. After unilateral optic nerve transection, or damage to the retina, the density of glial ETBreceptors in the optic nerve is significantly increased in all species examined. Thus, at 7 days posttransection there is a significant increase in ETBreceptors, and by 90 days posttransection the density of ETBreceptors in the rabbit or rat optic nerve was among the highest of any area in the central nervous system (CNS). Primary cultures of astrocytes or microglia, but not oligodendrocytes, express125I-ET-1 binding sites. These data demonstrate that in the normal CNS, astrocytes express low but detectable levels of ETBreceptors, and, after CNS injury, both astrocytes and microglia express high levels of ETBreceptors. ETBreceptors provide a therapeutic target for regulating glial proliferation and the release of neurotrophic factors from glia that occur in response to neuronal injury.