Calmodulin-mediated cadmium inhibition of phosphodiesterase activity, in vitro.
Ion-stripped bovine brain calmodulin (CaM) binds 4 moles Cd2+ as well as 4 moles Ca2+ per mole protein, with similar affinity; in the presence of 1 mM Mg2+ the molar binding ratio of CaM for Ca2+ decreased to 3, the apparent K0.5 for Ca2+ nearly doubled, but the binding characteristics of CaM for Cd2+ were not changed. Saturating concentrations Ca2+ did not affect the molar binding ratio of CaM for Cd2+, but increased the apparent K0.5 for Cd2+; vice versa, saturating concentrations Cd2+ decreased the molar binding ratio for Ca2+ to 2 without affecting the apparent K0.5 for Ca2+. CaM-independent phosphodiesterase (PDE) activity was inhibited at [Cd2+] greater than 10(-5) M. Cd2+-CaM as well as Ca2+-CaM activated PDE. However, the Cd2+-CaM complex is less effective than the Ca2+-CaM complex in stimulating CaM-dependent enzyme activities. Cd2+ inhibits Ca2+- and CaM-dependent PDE in a competitive way. Introduction of Cd2+ in a medium containing Ca2+ and CaM may, therefore, result in a reduction of CaM-dependent enzyme stimulation. By its interference with Ca2+- and CaM- dependent PDE activity, Cd2+ could upset the catabolic pathway of cellular cyclic nucleotide metabolism.
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002104:Cadmium / Q000378:metabolism / Q000494:pharmacology*; D002132:Calcium Radioisotopes; D002147:Calmodulin / Q000502:physiology*; D002417:Cattle; D000242:Cyclic AMP / Q000378:metabolism; D003720:Densitometry; D004591:Electrophoresis, Polyacrylamide Gel; D007202:Indicators and Reagents; D007700:Kinetics; D010726:Phosphodiesterase Inhibitors; D011868:Radioisotopes
D002132:Calcium Radioisotopes; D002147:Calmodulin; D007202:Indicators and Reagents; D010726:Phosphodiesterase Inhibitors; D011868:Radioisotopes; D002104:Cadmium; D000242:Cyclic AMP; D000469:Alkaline Phosphatase