The effect of amantadine (an antiparkinsonian agent) on calmodulin-dep
endent cyclic nucleotide phosphodiesterase isozymes was investigated.
Amantadine inhibited bovine brain 60 kDa calmodulin-dependent cyclic n
ucleotide phosphodiesterase but not the bovine brain 63 kDa, heart and
lung calmodulin-dependent cyclic nucleotide phosphodiesterase isozyme
s. The inhibition of bovine brain 60 kDa calmodulin-dependent cyclic n
ucleotide phosphodiesterase was overcome by increasing the concentrati
on of calmodulin. This suggests that amantadine may be an antagonist o
f calmodulin or act specifically and reversibly on the action of calmo
dulin. The bovine brain 60 kDa calmodulin-dependent cyclic nucleotide
phosphodiesterase isozyme is predominantly expressed in the brain and
its inhibition may result in increased intracellular levels of cyclic
AMP (cAMP). The increased intracellular levels of cAMP have a protecti
ve role for dopaminergic neurons. The present findings suggest that am
antadine may be a valuable tool to investigate the physiological role
of 60 kDa calmodulin-dependent cyclic nucleotide phosphodiesterase iso
zyme in the progression of Parkinson's disease and gives a new insight
into the action of this drug.