AMANTADINE - AN ANTIPARKINSONIAN AGENT INHIBITS BOVINE BRAIN 60 KDA CALMODULIN-DEPENDENT CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE ISOZYME

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.