Endothelins Promote the Activation of Astrocytes in Rat Neostriatum through ET_B Receptors

Abstract

The effects of endothelin (ET)-3 and an ET(B) receptor agonist on astrocytic activation in rat caudate putamen were examined by an immunohistochemical staining of glial fibrillary acidic protein (GFAP), a marker of reactive astrocytes. A single injection of 40 pmol ET-3 into rat caudate putamen increased the number of GFAP positive cells compared to that in the contralateral saline-injected side. Ala(1,3,11,15)-ET-1 (40 pmol), an ET(B) receptor agonist, also increased the number of striatal GFAP positive cells. The increases in GFAP positive cells were maximum (about 150% of the control side) in 1-2 weeks after injections of the ETs, and then reduced in 4 weeks. A continuous infusion of BQ788, an ET(B) receptor antagonist (23 nmol/day), into the lateral ventricle of the cerebrum antagonized the effect of Ala(1,3,11,15)-ET-1, while BQ788 also reduced the number of GFAP positive cells in saline-injected caudate putamen. Intrastriatal injection of 40 pmol Ala(1,3,11,15)-ET-1 did not affect the number of cells stained by B4 isolectin from Griffonia simplicifolia, which labels activated microglia/macrophages. Intraperitoneal administration of 5 mg/kg per day chloroquine and 0.2 mg/kg per day colchicine did not affect the action of Ala(1,3,11,15)-ET-1. These results suggest that activation of ET(B) receptors is involved in the induction of reactive astrocytes.

Absence of Glial Fibrillary Acidic Protein and Vimentin Prevents Hypertrophy of Astrocytic Processes and Improves Post-Traumatic Regeneration

“…The upregulation of endothelin B receptors by astrocytes in the injured CNS was proposed to be one of the steps leading to astrocyte activation and hypertrophy (Ishikawa et al, 1997;Baba, 1998;Koyama et al, 1999;Peters et al, 2003). By using Ab against endothelin B receptors, we found weak and almost exclusively endothelial immunostaining in the molecular layer of the dentate gyrus of the hippocampus on the side contralateral to entorhinal cortex lesion, fully comparable in wild-type and GFAP (Fig.…”

“…Hypertrophy of astrocytic processes in response to CNS trauma is normally accompanied by upregulation of endothelin B receptors (Ishikawa et al, 1997;Baba, 1998;Koyama et al, 1999;Peters et al, 2003). Moreover, it was suggested that blockage of endothelin B receptors may attenuate the formation of astrocytic glial scar , which does not fully develop in GFAP Ϫ/Ϫ Vim Ϫ/Ϫ mice .…”

The Genomic Response to Retinal Disease and Injury: Evidence for Endothelin Signaling from Photoreceptors to Glia

“…For example, EDNRB is induced in astrocytes after spinal cord compression injury or optic nerve transection (Rogers et al, 1997;Peters et al, 2003), injection of EDNRB agonists into the striatum promotes a reactive astrocytosis that can be blocked by an EDNRB-specific antagonist (Ishikawa et al, 1997), and local administration of an EDNRB-specific antagonist decreases the number of reactive astrocytes near the site of mechanical trauma in the adult brain or optic nerve (Koyama et al, 1999;. However, the published data regarding endothelins and endothelin receptors in CNS trauma models differ in a number of respects from the data reported here.…”

Regulations of Astrocytic Functions by Endothelins: Roles in the Pathophysiological Responses of Damaged Brains

“…Several reports indicate that ETs promote the conversion to reactive astrocytes through ET B receptors. The injection of Ala 1,3,11,15 -ET-1, a selective ET B receptor agonist, into the rat striatum increased the number of reactive astrocytes (6). Despite this activation of astrocytes, Ala 1,3,11,15 -ET-1 did not induce neuronal degradation or activate microglia, which indicates that the ET B agonist-induced astrocytic activation is not a consequence of neuronal damage.…”