Nephrol Dial Transplant (1993) 8: 748-753
© 1993 European Renal Association-European Dialysis and Transplant Association
research-article
Effect of cyclosporin A on endothelin synthesis by cultured human renal cortical epithelial cells
1Department of Medicine, UCL Medical School, The Rayne Institute Pond St, London, UK 2Department of Molecular Endocrinology, UCL Medical School Pond St, London, UK 3Department of Nephrology, The Royal Free Hospital Pond St, London, UK
Correspondence and offprint requests to: Correspondence and offprint requests to: Dr Albert Ong, Dept of Medicine, UCL Medical School, The Rayne Institute, University St, London WCIE 6JJ, UK.
We report here for the first time that human renal proximal tubular cells secrete endothelin, clear evidence of de-novo endothelin synthesis by these cells and the effect of cyclosponn A (C5A) on endothelin synthesis both in short-term (24 h) and medium-term (5-day) culture.
Human renal cortical epithelial cells were cultured and shown to possess proximal tubular characteristics. These cells produced endothelin in culture in a time- dependent manner, as measured by radioimmunoassay (291.6± 51.4 pg/well/24 h). Furthermore, endothelin production by these cells was significantly decreased by up to 80% by cycloheximide (1051.8± 54.9 pg/mg cell protein/24 h versus 253.2± 12.6 pg/mg cell protein/24 h), showing that these cells actively synthes ize endothelin. In short-term culture (24 h), CsA signi ficantly inhibited endothelin synthesis at a medium concentration of 10,000 
g/I. No change in endothelin synthesis was seen at lower CsA concentrations. In contrast, over a 5-day period, a non-significant increase in endothelin synthesis was observed at CsA concentra tions of 2000 g/I (152.5±20.4%); however, cell growth was significantly decreased at this concentration (71.33±6.39%). Using a newly developed two-site immunoradiometric assay specific for endothelin-l (ET-1), we demonstrate that ET-1 is the major endo thelin isoform produced by human renal proximal tubular cells.
Keywords: cyclosporin A; endothelin; tubular cells
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