Evidence for the activity of five adenosine-3',5'-monophosphate-degrading phosphodiesterase isozymes in the adult rat neocortex.
In the present study, the expression of the activity of adenosine-3',5'-monophosphate-degrading phosphodiesterases (cAMP-PDEs) was analyzed in rat neocortex homogenates. Following separation by anion-exchange chromatography, the isozymes were characterized by their sensitivity to modulators and by their kinetic properties. We identified the activity of five distinct cAMP-PDE isozymes: two calcium/calmodulin-dependent forms (PDE 1), one PDE 2 isozyme stimulated by guanosine-3',5'-monophosphate (cGMP), one cGMP-inhibited form (PDE 3) and a cAMP-specific, rolipram-sensitive form (PDE 4). Our study provides, for the first time, evidence for the existence of PDE 3 enzyme activity in rat neocortex and predicts the expression of at least two isoforms (splice variants) of PDE 1A in this brain area. The existence of different cAMP-degrading phosphodiesterases modulated by different intracellular second messengers (calcium and cGMP) suggests that the activity of neocortical neurons and glia cells is regulated, inter alia, by a 'crosstalk' between calcium-, cGMP- and cAMP-dependent second messenger pathways.
Institute of Physiology, University of Munich, Germany. bernd.sutor@lrz.uni-muenchen.de
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Sutor
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Mantell
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Bacher
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000302:isolation & purification* / Q000378:metabolism*; D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000302:isolation & purification* / Q000378:metabolism*; D000367:Age Factors; D000818:Animals; D000837:Anion Exchange Resins; D002118:Calcium / Q000502:physiology; D002147:Calmodulin / Q000502:physiology; D002852:Chromatography, Ion Exchange / Q000379:methods; D000242:Cyclic AMP / Q000378:metabolism* / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism* / Q000494:pharmacology; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6; D005136:Eye Proteins / Q000302:isolation & purification / Q000378:metabolism; D019579:Neocortex / Q000201:enzymology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D020889:Rolipram
D000837:Anion Exchange Resins; D002147:Calmodulin; D005136:Eye Proteins; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6; C096885:PDE6C protein, human; D006152:Cyclic GMP; D020889:Rolipram; D002118:Calcium