CULTURED ASTROCYTES RELEASE A FACTOR THAT DECREASES ENDOTHELIN-1 SECRETION BY BRAIN MICROVESSEL ENDOTHELIAL-CELLS

Endothelin-l (ET-1), originally characterized as a potent vasoconstric tor peptide secreted by vascular endothelial cells, has now been descr ibed to possess a wide range of biological activities within the cardi ovascular system and in other organs. Brain microvessel endothelial ce lls, which, together with perivascular astrocytes, constitute the bloo d-brain barrier, have been shown to secrete ET-1, whereas specific ET- 1 receptors are expressed on astrocytes. it is reported here that cond itioned medium from primary cultures of mouse embryo astrocytes could significantly, and reversibly, attenuate the accumulation of both ET-1 and its precursor big ET-1 in the supernatant of rat brain microvesse l endothelial cells by up to 59 and 76%, respectively, as assessed by immunometric assay. This inhibitor of ET-1 production was purified by gel-exclusion and ion-exchange chromatography as a 280-Da iron-contain ing molecule, able to release nitrites upon degradation. These results suggest that astrocytes, via release of an iron-nitrogen oxide comple x, may be involved in a regulatory loop of ET-1 production at the leve l of the blood-brain barrier.