title: Amantadine: an antiparkinsonian agent inhibits bovine brain 60 kDa calmodulin-dependent cyclic nucleotide phosphodiesterase isozyme.
abstract: The effect of amantadine (an antiparkinsonian agent) on calmodulin-dependent cyclic nucleotide phosphodiesterase isozymes was investigated. Amantadine inhibited bovine brain 60 kDa calmodulin-dependent cyclic nucleotide phosphodiesterase but not the bovine brain 63 kDa, heart and lung calmodulin-dependent cyclic nucleotide phosphodiesterase isozymes. The inhibition of bovine brain 60 kDa calmodulin-dependent cyclic nucleotide phosphodiesterase was overcome by increasing the concentration of calmodulin. This suggests that amantadine may be an antagonist of calmodulin or act specifically and reversibly on the action of calmodulin. 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 protective role for dopaminergic neurons. The present findings suggest that amantadine may be a valuable tool to investigate the physiological role of 60 kDa calmodulin-dependent cyclic nucleotide phosphodiesterase isozyme in the progression of Parkinson's disease and gives a new insight into the action of this drug.
authors.affiliation: Department of Pathology, Saskatoon Cancer Centre, University of Saskatchewan, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Kakkar
authors.forename: R V
authors.initials: RV
authors.lastname: Raju
authors.forename: A H
authors.initials: AH
authors.lastname: Rajput
authors.forename: R K
authors.initials: RK
authors.lastname: Sharma
mesh_terms: D000547:Amantadine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D000978:Antiparkinson Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001921:Brain / Q000201:enzymology*; D002147:Calmodulin / Q000494:pharmacology*; D002417:Cattle; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D007700:Kinetics; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*
chemical_list: D000978:Antiparkinson Agents; D002147:Calmodulin; D007527:Isoenzymes; D010726:Phosphodiesterase Inhibitors; D000547:Amantadine; D010727:Phosphoric Diester Hydrolases; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1