Expression of endothelin-B receptors by glia in vivo is increased after CNS injury in rats, rabbits, and humans

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 used ¹²⁵I-ET-1 to examine the expression of ET receptors both in vivo in the normal and transected optic nerves of the rabbit and rat and in vitro in cultures of astrocytes, microglia, or oligodendrocytes. Additionally, we examined the expression of ET receptors in the human optic nerve. Moderate levels of ET(B) receptors were identified in the rabbit and rat forebrain, whereas in the normal rabbit, rat, and human optic nerves a low density of ET(B) receptors 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 ET(B) receptors in the optic nerve is significantly increased in all species examined. Thus, at 7 days posttransection there is a significant increase in ET(B) receptors, and by 90 days posttransection the density of ET(B) receptors 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, express ¹²⁵-ET-1 binding sites. These data demonstrate that in the normal CNS, astrocytes express low but detectable levels of ET(B) receptors, and, after CNS injury, both astrocytes and microglia express high levels of ET(B) receptors. ET(B) receptors provide a therapeutic target for regulating glial proliferation and the release of neurotrophic factors from glia that occur in response to neuronal injury.