Effects of ruthenium red on activation of Ca2(+)-dependent cyclic nucleotide phosphodiesterase.
Ruthenium red inhibited Ca2(+)-dependent phosphodiesterase (Ca2(+)-PDE) selectively with an IC50 value of 15 microM. Increasing calmodulin concentration in the presence of both 100 microM and 4000 microM Ca2+ completely reversed the inhibition of Ca2(+)-PDE activity by ruthenium red. Ruthenium red-induced inhibition of Ca2(+)-PDE activity was also overcome by increasing the concentration of Ca2+ in the presence of both 200 ng and 2000 ng calmodulin, in sharp contrast to fluphenazine-induced inhibition of Ca2(+)-PDE. These results indicate that ruthenium red has distinct inhibitory mechanism which differs from that of calmodulin antagonists previously reported.
First Department of Internal Medicine, Mie University School of Medicine, Japan.
H
H
Masuoka
M
M
Ito
T
T
Nakano
M
M
Naka
T
T
Tanaka
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002118:Calcium / Q000502:physiology; D002147:Calmodulin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005476:Fluphenazine / Q000494:pharmacology; D006801:Humans; D009206:Myocardium / Q000201:enzymology; D010726:Phosphodiesterase Inhibitors; D012428:Ruthenium / Q000494:pharmacology*; D012430:Ruthenium Red / Q000494:pharmacology*
D002147:Calmodulin; D010726:Phosphodiesterase Inhibitors; D012430:Ruthenium Red; D012428:Ruthenium; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D005476:Fluphenazine; D002118:Calcium