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) whi ch induces hippocampal neuron death, and in human brains with Alzheime r disease, were mapped by quantitative in vitro autoradiography employ ing [I-125]ET-1 as a radioligand. Rats were decapitated 4 or 7 days af ter ischemia. In the rat brain, the [I-125]ET-1 binding sites were rem arkably increased in the hippocampal CA1 and dentate gyrus, ventral th alamic nucleus, and cortical vessels 4 and 7 days after ischemia, when many reactive astroglia were observed. The [I-125]ET-1 binding sites decreased in the cerebral cortex affected by Alzheimer disease. The bi nding was abolished by 1 mu M unlabeled ET-1, ET-3 sarafotoxin S6b, an d BQ788 (an ET(B) antagonist) but not by BQ123 (an ET(A) antagonist), suggesting that the [I-125]ET-1 binding sites are as ET(B) receptors. The present findings raise the possibility that a glial ET system coul d be responsible for the occurrence of ischemic neuron cell death.