Action and binding of the endothelin antagonist bosentan on astrocytes of cultured rat central nervous system. Electrophysiological and autoradiographic studies

Abstract Our autoradiographic studies demonstrate that astrocytes in explant cultures of rat central nervous system possess binding sites for the first orally active, mixed, nonpeptide endothelin receptor antagonist [ 3 H]bosentan. Binding of [ 3 H]bosentan was inhibited by unlabelled bosentan and endothelin-1 at high concentrations, suggesting specific binding of the antagonist. Electrophysiological studies have revealed that bosentan reversibly blocked the depolarizations by endothelin but not by angiotensin II, indicating that the antagonist specifically antagonizes the action of endothelin on the glial membrane. This is consistent with biochemical studies from other laboratories demonstrating that bosentan did not interfere with binding of angiotensin II. The availability of bosentan, a potent and selective endothelin receptor antagonist should help to elucidate the role of endothelin on astrocyte function.