FK506 regulates Ca2+ release evoked by inositol 1,4,5-trisphosphate independently of FK-binding protein in endothelial cells.

摘要: Background and purpose FK506 rapamycin are modulators of FK-binding proteins (FKBP) that used to suppress immune function after organ hematopoietic stem cell transplantations. The drugs share the unwanted side-effect evoking hypertension is associated with reduced endothelial nitric oxide production. underlying mechanisms not understood. FKBP may regulate IP3 receptors (IP3 R) ryanodine (RyR) alter Ca2+ signalling in cells. Experimental approach We investigated effects on release via R RyR hundreds cells, using indicator Cal-520, intact mesenteric arteries from male Sprague-Dawley rats. Rs were activated by acetylcholine or localised photo-uncaging , caffeine. Key results While FKBPs present, modulation did -evoked release. Conversely, FK506, which modulates blocks calcineurin, increased Inhibition calcineurin (okadiac acid cypermethrin) also blocked effects. When was inhibited, These findings suggest modulated FKBP, but FK506-mediated inhibition. caffeine failed suggesting functional native endothelium. Conclusion implications hypertensive immunosuppressant rapamycin, while mediated do appear be exerted at documented cellular targets altered binding RyR.