Endothelin-1 directly modulates its own secretion: studies utilising the cell immunoblot technique.
Endothelin-1 is an important factor in vasoregulation and circulating levels of the peptide are increased in a number of cardiovascular disorders. However, control of endothelin-1 secretion is only sketchily understood. The possibility that endothelin-1 influences its own release was investigated. A cell immunoblot method, which can detect local secretion of peptide from individual human vascular endothelial cells, was employed. Cells were dispersed onto a protein-binding membrane. Endothelin-1 in cells or secreted and adhering to the protein-binding membrane outside the cells was detected using immunohistochemical techniques. The numbers of cells that contained endothelin-1 and secreted endothelin-1 were counted after the cells had been incubated in control conditions, or with added endothelin-1, angiotensin-II, or endothelin receptor antagonists, bosentan and BQ788. Endothelin-1 and angiotensin-II increased the numbers of cells that secreted endothelin-1. On the other hand, bosentan and BQ788 caused a reduction in the numbers of endothelin-1-secreting cells. These results indicate that human endothelial cells contain a pathway by which endothelin-1 induces its own release. The receptor antagonists, bosentan and BQ788, inhibited basal secretion of endothelin-1.
Evans
John J
JJ
Department of Obstetrics and Gynaecology, Christchurch School of Medicine and Health Sciences, Christchurch Women's Hospital, Private Bag 4711, Christchurch, New Zealand. john.evans@chmeds.ac.nz
Youssef
Alber H
AH
Yandle
Timothy G
TG
Lewis
Lynley K
LK
Nicholls
M Gary
MG
D000804:Angiotensin II / Q000494:pharmacology; D000077300:Bosentan; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000187:drug effects / Q000378:metabolism* / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting / Q000379:methods; D009842:Oligopeptides / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology
D019332:Endothelin-1; D009842:Oligopeptides; D010880:Piperidines; D013449:Sulfonamides; D000804:Angiotensin II; C086539:BQ 788; D000077300:Bosentan