ENDOTHELIN-1 AS A MEDIATOR OF ENDOTHELIAL CELL-PERICYTE INTERACTIONS IN BOVINE BRAIN CAPILLARIES

Endothelial cells and pericytes are closely associated in brain capill aries. Together with astrocytic foot processes, they form the blood-br ain barrier, Capillaries were isolated from bovine brain cortex. Pure populations of endothelial cells and pericytes were isolated and cultu red in vitro. Polarized monolayers of endothelial cells preferentially secreted immunoreactive endothelin-1 (Et-1) at their abluminal (brain -facing) membrane, They did not express receptors for Et-1. Pericytes expressed BQ-123-sensitive ETA receptors for endothelins as evidenced by I-125-Et-1 binding experiments. These receptors were coupled to pho spholipase C as demonstrated by intracellular calcium measurements usi ng indo-1-loaded cells. Addition of Et-1 to pericytes induced marked c hanges in the cell morphology that were associated with a reorganizati on of F-actin and intermediate filaments. It is concluded that Et-1 is a paracrine mediator at the bovine blood-brain barrier and that capil lary pericytes are target cells for endothelium-derived Et-1.