Secretion of immunoreactive endothelin-1 by capillary and microvascular endothelium of human brain.
Modulation of immunoreactive endothelin-1 (IR-ET-1) production by vasoactive substances was investigated in cultured endothelial cells (EC) derived from capillaries and microvessels of human brain. Peptides, catecholamines, thrombin, protein kinase C-activating phorbol ester, and calcium ionophore enhanced the secretion of IR-ET-1. The known vasoconstrictive peptides, angiotensin II (Ang II) and arginine-vasopressin (AVP) dose-dependently stimulated the endothelial secretion of IR-ET-1. The angiotensin and vasopressin-inducible production of IR-ET-1 was completely inhibited by their respective receptor antagonists [Sar1, Ala8]-angiotensin II and [1-6 (beta-mercapto-beta,beta-cyclopentamethylene propionic acid), 2-O-methyl-tyrosine]. The results indicate that the peptide-stimulated secretion of IR-ET-1 is receptor-mediated in EC which have specific angiotensin II and arginine-vasopressin receptors. These findings represent the first demonstration of IR-ET-1 production by capillary and microvascular endothelium of human brain.
Bacic
F
F
Stroke Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892.
Uematsu
S
S
McCarron
R M
RM
Spatz
M
M
D000804:Angiotensin II / Q000494:pharmacology; D001127:Arginine Vasopressin / Q000494:pharmacology; D001921:Brain / Q000098:blood supply*; D002196:Capillaries / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism; D002478:Cells, Cultured; D016232:Endothelins / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008833:Microcirculation / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism
D002395:Catecholamines; D016232:Endothelins; D010455:Peptides; D000804:Angiotensin II; D001127:Arginine Vasopressin; D011493:Protein Kinase C; D013917:Thrombin