Cyclosporine increases endothelin-1 binding site density in cardiac cell membranes.
When used in high concentrations, the immunosuppressive agent cyclosporine A has toxic side effects, including cardiac fibrosis and calcification. Cyclosporine-treated mice were used to investigate whether a cyclosporine dose regime which produces cardiac fibrosis and calcification alters the density of the specific binding sites for the endothelial-derived vasoconstrictor polypeptide, endothelin-1. After twenty-one days of treatment the endothelin-1 binding site density in cardiac cell membranes was increased, without any change in selectivity. This increase in endothelin-1 binding site density could contribute to the cytotoxic effects of cyclosporine.
Nayler
W G
WG
Department of Medicine, University of Melbourne, Austin Hospital, Victoria, Australia.
Gu
X H
XH
Casley
D J
DJ
Panagiotopoulos
S
S
Liu
J
J
Mottram
P L
PL
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D003524:Cyclosporins / Q000494:pharmacology* / Q000633:toxicity; D016232:Endothelins; D004730:Endothelium, Vascular; D006321:Heart / Q000187:drug effects; D007700:Kinetics; D051379:Mice; D008808:Mice, Inbred CBA; D009206:Myocardium / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D017466:Receptors, Endothelin; D012016:Reference Values
D003524:Cyclosporins; D016232:Endothelins; D010455:Peptides; D011956:Receptors, Cell Surface; D017466:Receptors, Endothelin