[The mechanism of inhibition of calmodulin-dependent cyclic nucleotide phosphodiesterase by dihydropyridine calcium antagonists].
Kinetic studies of the monoclonal antibody-purified 60 kd calmodulin dependent cyclic nucleotide phosphodiesterase (PDE) from bovine brain indicate that the dihydropyridine calcium antagonists, nicardipine and felodipine are partially competitive inhibitors of the enzyme. This was supported by the facts that the inhibition approached a finite level as the concentrations of drug reached saturation and the inhibition showed non-linearity characteristics in the Dixon plot. Furthermore, at the constant concentration of felodipine which brings about close to maximal inhibition, increasing concentrations of nicardipine can alleviate enzyme inhibition to approach the level of maximal nicardipine inhibition, suggesting that the calmodulin-dependent PDE may contain specific dihydropyridine binding site distinct from the active site.
Wu
Z
Z
Dept Biochem, Univ Calgary, Alberta, Canada.
Sharma
R K
RK
Wang
J H
JH
D001667:Binding, Competitive; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D015736:Felodipine / Q000494:pharmacology*; D009529:Nicardipine / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism
D010726:Phosphodiesterase Inhibitors; D009529:Nicardipine; D010727:Phosphoric Diester Hydrolases; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D015736:Felodipine