Action of endothelin-1 on rat astrocytes through the ETB receptor.
We investigated the effect of ET-1 on the state of rat cerebral astrocytes (AC) differentiation. AC ceased to proliferate and changed into its differentiated state by treatment with dibutyryl cyclic AMP (DBcAMP). The cell growth activity in DBcAMP-treated AC was stimulated by ET-1 in a dose-dependent manner. Over similar dose ranges, ET-1 suppressed the glutamine synthetase activity in DBcAMP-treated AC. The molar potency of ET-1 in this action was at least 3 orders of magnitude higher than that in mitogenic action in AC under the proliferative state previously reported. Northern blot analysis revealed that ETB receptor mRNA level in DBcAMP-treated AC was markedly higher than that in AC untreated with DBcAMP. Consistently, binding studies showed that the Bmax value for [125I]ET-1 in DBcAMP-treated AC was 16 times higher than that in AC untreated with DBcAMP. These results suggest that ET-1 potently induced a retraction of the differentiation state of AC from fully the specialized state and that the high responsiveness of differentiated AC to ET-1 was partly attributed to the high level expression of the ETB receptor.
Hama
H
H
Department of Environmental Medicine, University of Tsukuba, Ibaraki, Japan.
Sakurai
T
T
Kasuya
Y
Y
Fujiki
M
M
Masaki
T
T
Goto
K
K
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D015152:Blotting, Northern; D001921:Brain / Q000166:cytology / Q000502:physiology; D003994:Bucladesine / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016232:Endothelins / Q000378:metabolism / Q000494:pharmacology*; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D007700:Kinetics; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D017466:Receptors, Endothelin
D016232:Endothelins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017466:Receptors, Endothelin; D012313:RNA; D003994:Bucladesine; D005974:Glutamate-Ammonia Ligase