Cultured Astrocytes Release a Factor that Decreases Endothelin-1 Secretion by Brain Microvessel Endothelial Cells |
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Authors: | C. Fé dé rici,L. Camoin,C. Cré minon,N. Chaverot,A. D. Strosberg, P. O. Couraud |
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Affiliation: | Laboratoire d'Immuno-Pharmacologie Moléculaire, ICGM, CNRS UPR 0415, UniversitéParis VII, Paris, and; CEA SPI/DRIPP, CE Saclay, Gif-sur-Yvette, France |
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Abstract: | Abstract: Endothelin-1 (ET-1), originally characterized as a potent vasoconstrictor peptide secreted by vascular endothelial cells, has now been described to possess a wide range of biological activities within the cardiovascular system and in other organs. Brain microvessel endothelial cells, which, together with perivascular astrocytes, constitute the blood-brain barrier, have been shown to secrete ET-1, whereas specific ET-1 receptors are expressed on astrocytes. It is reported here that conditioned 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 microvessel 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-containing molecule, able to release nitrites upon degradation. These results suggest that astrocytes, via release of an iron-nitrogen oxide complex, may be involved in a regulatory loop of ET-1 production at the level of the blood-brain barrier. |
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Keywords: | Endothelin Astrocytes Brain endothelial cells Nitric oxide |
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