Multiple molecular forms of cyclic nucleotide phosphodiesterase in cardiac and smooth muscle and in platelets: Isolation, characterization, and effects of various reference phosphodiesterase inhibitors and cardiotonic agents

Cyclic Nucleotide Phosphodiesterases: Properties, Activators, Inhibitors, Structure–Activity Relationships, and Possible Role in Drug Development

Stimulation of a low Km phosphodiesterase from liver by insulin and glucagon.

I. Introduction ACOMPLEX array of signals from the extracellular environment regulate many cell processes, including the entry and exit from the mitotic cycle and the induction and maintenance of differentiation (1–3). Cells elaborate these external stimuli via receptors, transducers, and second messengers (4, 5) which control intricate circuits that lead to protein phosphorylation by protein kinases (6, 7). Although novel second messenger pathways have been discovered and dissected in some detail in the past 10 years (8, 9), cyclic nucleotides (cAMP and cGMP) remain the best characterized second messengers, and their role in the differentiation and control of metabolic processes of the endocrine cell is widely recognized. The components of the membrane-associated machinery that transduces external signals into changes in cyclic nucleotide levels have been isolated and characterized. These include many members of the family of membrane receptors (10–14), G proteins acting as transducers (15, 16), and aden...

Hormonal Regulation of Cyclic Nucleotide Phosphodiesterases

Cyclic nucleotide phosphodiesterase activity plays an important role in cellular function. A variety of cellular activities are regulated through mechanisms controlling the level of cyclic AMP or cyclic GMP. These mechanisms include synthesis, degradation, efflux, and sequestration of cyclic nucleotides within the cell. Hydrolysis by phosphodiesterase is the unique mechanism for the degradation of the cyclic nucleotides. Despite their ubiquitous occurrence in biological systems, the cyclic nucleotides are not known to be substrates for any other enzymatic reaction.

T.R. Russell

Papers

Separate Phosphodiesterases for the Hydrolysis of Cyclic Adenosine 3',5'-Monophosphate and Cyclic Guanosine 3',5'-Monophosphate in Rat Liver