INHIBITION OF BOVINE BRAIN CALMODULIN-DEPENDENT CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE ISOZYMES BY DEPRENYL

Intracellular concentrations of cyclic nucleotides is regulated by cyc lic nucleotide phosphodiesterases and calmodulin-dependent cyclic nucl eotide phosphodiesterases (CaMPDE), one of the most intensively studie d and best characterized phosphodiesterases. In the present study, the effect of an antiparkinsonian agent, deprenyl (selegeline hydrochlori de) which is believed to be a selective inhibitor of monoamine oxidase -B, on bovine brain calmodulin-dependent cyclic nucleotide phosphodies terase (CaMPDE) isozymes have been investigated. The findings indicate d that deprenyl inhibited brain 60kDa isozyme, however the inhibition for brain 63kDa CaMPDE was observed to a lesser extent. The inhibition of brain 60kDa CaMPDE was overcome by increasing the concentration of calmodulin suggesting that deprenyl may be calmodulin antagonist or a ct specifically and reversibly on the action of calmodulin. The 60kDa CaMPDE isozyme is predominantly expressed in brain and its inhibition can result in increased intracellular levels of cAMP. The increased in tracellular levels of cAMP have a protective role for dopaminergic neu rons. Therefore, deprenyl may be a valuable tool to investigate the ph ysiological roles of brain CaMPDE isozymes in progression of Parkinson 's disease and gives a new insight into the action of this drug.