Cultured astrocytes release a factor that decreases endothelin-1 secretion by brain microvessel endothelial cells.
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.
Fédérici
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C
Laboratoire d'Immuno-Pharmacologie Moléculaire, ICGM, CNRS UPR 0415, Université Paris VII, France.
Camoin
L
L
Créminon
C
C
Chaverot
N
N
Strosberg
A D
AD
Couraud
P O
PO
D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D001812:Blood-Brain Barrier; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology; D003342:Corpus Striatum / Q000166:cytology / Q000196:embryology; D010450:Endopeptidases / Q000378:metabolism; D016232:Endothelins / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism*; D066298:In Vitro Techniques; D007501:Iron / Q000737:chemistry; D051379:Mice; D009573:Nitrites / Q000737:chemistry; D051381:Rats
D016232:Endothelins; D009573:Nitrites; D007501:Iron; D010450:Endopeptidases