Abstract
Chronic treatment with the immunosuppressive drug Cyclosporine A (CsA) is associated with increased intracellular calcium in vascular smooth muscle cells, which may activate phospholipase A2. We used rat aortic endothelial cells to investigate the role of protein kinase C (PKC) in CsA-induced prostacyclin (PGI2) release. CsA (10−9M) produced a significant increase in PGI2release. CsA-induced PGI2release were inhibited 80–85 % by 10−9M, and 99–100 % by 10−6M pretreatment doses of any of three different PKC inhibitors, i.e. 1-(5-isoquinolinesulfonylmethyl)piperazine(H7), staurosporine or 1-(5-isoquinolinesulfonyl)piperazine. Pretreatment with (10−9M) of diltiazem (a voltage-sensitive L-type calcium channel blocker) completely inhibited both CsA-induced PGI2release. Conversely, pretreatment with (10−9M) of thapsigargin (an intracellular calcium channel blocker) did not alter the action of CsA. These results strongly suggest that PKC, in association with an influx of extracellular calcium, mediates CsA-induced PGI2release in rat aortic endothelial cells.Cyclosporine A; 1-(5-isoquinolinemethyl)piperazine(H7); staurosporine; 1-(5-isoquinolinesulfonyl)piperazine; diltiazem; thapsigargin; rat aortic endothelial cells.
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