Calcineurin phosphatase activity and immunosuppression. A review on the role of calcineurin phosphatase activity and the immunosuppressive effect of cyclosporin A and tacrolimus.
The mode of immunosuppressive action of tacrolimus (FK506) and cyclosporin A has been elucidated. Both drugs bind to proteins in the cytoplasm to form complexes, which in turn inhibit the phosphatase activity of calcineurin, an important limiting step in the activation of T cells. The association between drug uptake (pharmacokinetics) and enzyme inhibition (pharmacodynamics) is under current investigation. Great variations in the correlation between blood drug levels and enzyme inhibition could indicate that monitoring calcineurin phosphatase activity for treatment might be superior to monitoring blood drug levels.
Jørgensen
K A
KA
Research Laboratory, Department of Renal Medicine C, Skejby Sygehus, Arhus University Hospital, Arhus N, Denmark. kaj@dadlnet.dk
Koefoed-Nielsen
P B
PB
Karamperis
N
N
D000595:Amino Acid Sequence; D016572:Cyclosporine / Q000494:pharmacology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D016559:Tacrolimus / Q000494:pharmacology*; D014181:Transplantation Immunology / Q000276:immunology
D007166:Immunosuppressive Agents; D016572:Cyclosporine; C120817:calcineurin phosphatase; D010744:Phosphoric Monoester Hydrolases; D016559:Tacrolimus