Inhibition of bovine brain calmodulin-dependent cyclic nucleotide phosphodiesterase isozymes by deprenyl.
Intracellular concentrations of cyclic nucleotides is regulated by cyclic nucleotide phosphodiesterases and calmodulin-dependent cyclic nucleotide phosphodiesterases (CaMPDE), one of the most intensively studied and best characterized phosphodiesterases. In the present study, the effect of an antiparkinsonian agent, deprenyl (selegeline hydrochloride) which is believed to be a selective inhibitor of monoamine oxidase-B, on bovine brain calmodulin-dependent cyclic nucleotide phosphodiesterase (CaMPDE) isozymes have been investigated. The findings indicated that deprenyl inhibited brain 60 kDa isozyme, however the inhibition for brain 63 kDa CaMPDE was observed to a lesser extent. The inhibition of brain 60 kDa CaMPDE was overcome by increasing the concentration of calmodulin suggesting that deprenyl may be calmodulin antagonist or act specifically and reversibly on the action of calmodulin. The 60 kDa CaMPDE isozyme is predominantly expressed in brain and its inhibition can result in increased intracellular levels of cAMP. The increased intracellular levels of cAMP have a protective role for dopaminergic neurons. Therefore, deprenyl may be a valuable tool to investigate the physiological roles of brain CaMPDE isozymes in progression of Parkinson's disease and gives a new insight into the action of this drug.
Kakkar
R
R
Department of Pathology, Saskatoon Cancer Centre, Canada.
Raju
R V
RV
Rajput
A H
AH
Sharma
R K
RK
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D002147:Calmodulin / Q000494:pharmacology; D002417:Cattle; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D012642:Selegiline / Q000494:pharmacology*
D000978:Antiparkinson Agents; D002147:Calmodulin; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D012642:Selegiline; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1