ACTION AND BINDING OF THE ENDOTHELIN ANTAGONIST BOSENTAN ON ASTROCYTES OF CULTURED RAT CENTRAL-NERVOUS-SYSTEM - ELECTROPHYSIOLOGICAL AND AUTORADIOGRAPHIC STUDIES

Our autoradiographic studies demonstrate that astrocytes in explant cu ltures of rat central nervous system possess binding sites for the fir st orally active, mixed, nonpeptide endothelin receptor antagonist [H- 3]bosentan. Binding of [H-3]bosentan was inhibited by unlabelled bosen tan and endothelin-l at high concentrations, suggesting specific bindi ng 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 antagon izes the action of endothelin on the glial membrane. This is consisten t with biochemical studies from other laboratories demonstrating that bosentan did not interfere with binding of angiotensin II. The availab ility of bosentan, a potent and selective endothelin receptor antagoni st should help to elucidate the role of endothelin on astrocyte functi on.