Cortical expression of endothelin receptor subtypes A and B following middle cerebral artery occlusion in rats

This work aimed to define the spatial expression of endothelin A (ETA) and B (ETB) receptors in the cerebral cortex after permanent middle cerebral artery occlusion (MCAO) and to identify the phenotype of cells expressing ETA and ETB receptors. Cortical expression of ETA and ETB receptors was determined at the mRNA level by semi-quantitative reverse transcription-polymerase chain reaction and at the protein level by immunofluorescence staining, 12, 24 and 72 h after MCAO. Cells expressing endothelin receptors were phenotyped by double labelling with antibodies, anti-protein gene product (PGP9.5) and anti-ED1, towards neurons and activated microglia/macrophages, respectively. Both ETA and ETB receptor mRNA expressions increased significantly in the ipsilateral cortex in a time-dependent manner after MCAO. Robust expression of ETA receptors was noted in most neurons of the ischemic core and in several neurons in laminae 3 and 4 of the peri-infarct region 24 and 72 h after MCAO. ETB receptor immunoreactivity was observed in activated microglia/macrophages, beginning 24 h after MCAO. These results provide the first evidence that the action of endothelin during ischermia may be mediated by neuronal ETA receptors and activated microglia/macrophage ETB receptors. This differential localization of ETA and ETB receptors suggests that endothelin is involved in some complex neuron-glial interactions in addition to its vascular modulatory activity during ischemia. ((C) 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved.