Endothelin (ET) binding sites in male Wistar rat brains subjected to a 20-min four-vessel occlusion (transient forebrain ischemia model) which induces hip-pocampal 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 μM unlabeled ET-1, ET-3, sarafotoxin S6b, and BQ788 (an ETBantagonist) but not by BQ123 (an ETAantagonist), suggesting that the [125I]ET-1 binding sites are as ETBreceptors. The present findings raise the possibility that a glial ET system could be responsible for the occurrence of ischemic neuron cell death.
- Endothelin receptor
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine