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 astrocyte s express functional endothelin (ET) receptors. To determine if simila r ET receptors are expressed by adult glia we used I-125-ET-1 to exami ne the expression of ET receptors both in vivo in the normal and trans ected optic nerves of the rabbit and rat and in vitro in cultures of a strocytes, microglia, or oligodendrocytes, Additionally, we examined t he expression of ET receptors in the human optic nerve, Moderate level s of ETB receptors were identified in the rabbit and rat forebrain, wh ereas in the normal rabbit, rat, and human optic nerves a low density of ETB receptors was observed, mainly in association with glial fibril lary acidic protein + (GFAP+) astrocytes. After unilateral optic nerve transection, or damage to the retina, the density of glial ETB recept ors in the optic nerve is significantly increased in all species exami ned. Thus, at ? days posttransection there is a significant increase i n ETB receptors, and by 90 days posttransection the density of ETB rec eptors In the rabbit or rat optic nerve was among the highest of any a rea in the central nervous system (CNS), Primary cultures of astrocyte s or microglia, but not oligodendrocytes, express I-125-ET-1 binding s ites. These data demonstrate that in the normal CNS, astrocytes expres s low but detectable levels of ETB reeeptors, and, after CNS injury, b oth astrocytes and microglia express high levels of ETB receptors. ETB receptors provide a therapeutic target for regulating glial prolifera tion and the release of neurotrophic factors from glia that occur in r esponse to neuronal injury. (C) 1997 Academic Press.