Endothelin (ET)-1 and its receptors (ETA and ETB receptor) are present in the central nervous system and ET exerts biological effects on gliogenesis and glial cell functions. To define a possible mechanismby ETA receptor signaling, the distribution of...
Endothelin (ET)-1 and its receptors (ETA and ETB receptor) are present in the central nervous system and ET exerts biological effects on gliogenesis and glial cell functions. To define a possible mechanismby ETA receptor signaling, the distribution of ETA receptor in developing oligodendrocytes and the effects of ET-1 on the myelination of oligodendrocytes precursor cells (OPCs) were examined first. ETA receptor was expressed in the capillary wall during early postnatal development; however later in the development, ETA receptor was expressed in the myelinating stages of oligodendrocytes development. ET-1 induced myelin basic protein (MBP) in primary OPCs culture exerts its biological effect though the ETA receptor and is blocked by ETA receptor antagonist. In addition, ET-1 evokes the release of Ca2+ which is a central regulator of oligodendrocyte differentiation. Our results, which provide a mechanistic link between endothelin and its ETA receptor and myelination, a mediator of OPC differentiation associated with demyelinating pathologies and specific signaling pathways amenable to pharmacological manipulation, therefore havesignificant potential for developing future strategies for enhancing CNS remyelination.