Endothelin receptors in ischemic rat brain and Alzheimer brain.
Endothelin (ET) binding sites in male Wistar rat brains subjected to a 20-min four-vessel occlusion (transient forebrain ischemia model) which induces hippocampal neuron death, and in human brains with Alzheimer disease, were mapped by quantitative in vitro autoradiography employing [125I]ET-1 as a radioligand. Rats were decapitated 4 or 7 days after ischemia. In the rat brain, the [125I]ET-1 binding sites were remarkably increased in the hippocampal CA1 and dentate gyrus, ventral thalamic nucleus, and cortical vessels 4 and 7 days after ischemia, when many reactive astroglia were observed. The [125I]ET-1 binding sites decreased in the cerebral cortex affected by Alzheimer disease. The binding was abolished by 1 microM unlabeled ET-1, ET-3, sarafotoxin S6b, and BQ788 (an ETB antagonist) but not by BQ123 (an ETA antagonist), suggesting that the [125I]ET-1 binding sites are as ETB receptors. The present findings raise the possibility that a glial ET system could be responsible for the occurrence of ischemic neuron cell death.
Kohzuki
M
M
Section of Internal Medicine and Disability Prevention, Tohoku University Graduate School, Sendai, Japan.
Onodera
H
H
Yasujima
M
M
Itoyama
Y
Y
Kanazawa
M
M
Sato
T
T
Abe
K
K
D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002545:Brain Ischemia / Q000378:metabolism*; D016232:Endothelins / Q000378:metabolism; D006801:Humans; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017466:Receptors, Endothelin / Q000032:analysis*
D016232:Endothelins; D017466:Receptors, Endothelin