Molecular properties of cyclic nucleotide phosphodiesterase isozymes.
Mammalian cells contain multiple molecular forms of cyclic nucleotide phosphodiesterase that differ in substrate specificity and kinetic and regulatory properties. Calcium/calmodulin and cyclic GMP are important regulators of the hydrolysis of cyclic AMP by either stimulating or inhibiting the activity of distinct forms of phosphodiesterase. Several isozymes of cyclic nucleotide phosphodiesterase have been purified to apparent homogeneity. Although some sequence homology is observed the isozymes appear genetically distinct by immunological criteria. Cyclic AMP- and calmodulin-dependent protein kinases can phosphorylate these enzymes and alter their kinetic and regulatory properties. Both tissue specificity and pharmacological selectivity of isozymes have been demonstrated for several drugs. In certain cases, e.g. cardiac muscle, the selective inhibition of a high affinity cAMP phosphodiesterase activity in a specific subcellular fraction correlates with pharmacologic responses. The results from molecular and pharmacologic studies of cyclic nucleotide phosphodiesterases have indeed expanded the role this system of isoenzymes exerts in the regulation of cellular function.
Strada
S J
SJ
Department of Pharmacology, University of South Alabama College of Medicine, Mobile 36608.
Kithas
P A
PA
Whalin
M E
ME
Thompson
W J
WJ
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000502:physiology; D002147:Calmodulin / Q000502:physiology; D006152:Cyclic GMP / Q000494:pharmacology; D003600:Cytosol / Q000201:enzymology; D004285:Dogs; D007328:Insulin / Q000502:physiology; D007527:Isoenzymes / Q000378:metabolism*; D051381:Rats
D002147:Calmodulin; D007328:Insulin; D007527:Isoenzymes; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D006152:Cyclic GMP; D002118:Calcium