[Astrocytes and endothelins: possibilities for tissue-repair in damaged central nervous system].
Endothelins and their receptor of type B (ETBR) that couples with G-protein are widely distributed in the mammalian central nervous system (CNS). ETBR mainly exists on astrocytes, and endothelins exert mitogenic action on astrocytes through stimulation of the receptor. The intracellular signaling of ETBR in astrocytes is converged in the activation of mitogen-activated protein kinase through a protein kinase C-dependent pathway and a pertussis toxin-sensitive G-protein-mediated pathway. We demonstrated that cultured astrocytes. When differentiated and growth-arrested by treatment with dibutyryl cyclic AMP, abundantly expressed ETBR and these cells immediately entered into a proliferative state in response to endothelin-1 at the plasma level. This has the following physiological implication in vivo: plasma-derived endothelin-1 intrudes into parenchyme upon CNS damage, and it initiates astrogliosis through activation of ETBR. We used two models of CNS injury in rats. The first is a brain edema model induced by cold-injury, and the second is a spinal cord injury model, both of which allow plasma to exude into the injured tissues and subsequently trigger sequential proliferative responses of astrocytes after the injury. Anti-endothelin monoclonal antibody and SB209670, an endothelin receptor antagonist, specifically and potently inhibited astrocytic proliferation 24 hr after the injury. It is concluded that endothelin-1 plays a key role for initiation of astrocytic proliferation in the acute phase of CNS damage.
Hama
H
H
Department of Pharmacology, University of Tsukuba, Ibaraki, Japan.
Uesugi
M
M
Kasuya
Y
Y
Goto
K
K
D001253:Astrocytes / Q000502:physiology*; D002478:Cells, Cultured; D002490:Central Nervous System / Q000293:injuries*; D016232:Endothelins / Q000502:physiology*; D017466:Receptors, Endothelin / Q000502:physiology
D016232:Endothelins; D017466:Receptors, Endothelin