Transient hypoxia/hypoglycemia upregulates endothelin B receptors in cultured rat astrocytes

Endothelins are potent vasoactive peptides that bind to their specific rece ptors, playing an important role in the CNS under physiological and pathoph ysiological conditions. Astrocytes, which have been shown to express these receptors, also have a considerable role to play under physiological and pa thophysiological conditions, particularly those involved in delayed neurona l death. We carried out in vitro receptor autoradiographic binding experime nts using specific ligands for endothelin receptors on cultured rat; astroc ytes. On astrocytes, the specific binding sites for I-125-PD151242 (a selec tive endothelin A receptor antagonist) and I-125-IRL 1620 (a selective endo thelin B receptor agonist) were detected. We also characterized the qualita tive and quantitative changes of endothelin receptors 24 h after subjecting cultured rat astrocytes to a transient 4-h hypoxia/hypoglycemia insult, us ed as a model of delayed neuronal death. After transient hypoxia/hypoglycem ia, the number of endothelin B receptors increased significantly on culture d astrocytes, but this did not occur among the endothelin A receptors. Thes e findings suggest that the astrocytic effects associated with endothelin i n delayed neuronal death include gliosis or the repair process or both, man ifested primarily by an increase in the number of endothelin B receptors. T his rise does not require interaction with other types of CNS cells. Endoth elin A receptors might have a role taking their number into consideration o n rat astrocytes under both physiological and pathophysiological conditions . (C) 2000 Wiley-Liss, Inc.