R. Kakkar et al., INHIBITION OF BOVINE BRAIN CALMODULIN-DEPENDENT CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE ISOZYMES BY DEPRENYL, Life sciences, 59(21), 1996, pp. 337-341
Citations number
20
Categorie Soggetti
Biology,"Medicine, Research & Experimental","Pharmacology & Pharmacy
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.