title: Cyclic nucleotide phosphodiesterases (PDEs): coincidence detectors acting to spatially and temporally integrate cyclic nucleotide and non-cyclic nucleotide signals.
abstract: The cyclic nucleotide second messengers cAMP and cGMP each affect virtually all cellular processes. Although these hydrophilic small molecules readily diffuse throughout cells, it is remarkable that their ability to activate their multiple intracellular effectors is spatially and temporally selective. Studies have identified a critical role for compartmentation of the enzymes which hydrolyse and metabolically inactivate these second messengers, the PDEs (cyclic nucleotide phosphodiesterases), in this specificity. In the present article, we describe several examples from our work in which compartmentation of selected cAMP- or cGMP-hydrolysing PDEs co-ordinate selective activation of cyclic nucleotide effectors, and, as a result, selectively affect cellular functions. It is our belief that therapeutic strategies aimed at targeting PDEs within these compartments will allow greater selectivity than those directed at inhibiting these enzymes throughout the cells.
authors.forename: Donald H
authors.initials: DH
authors.lastname: Maurice
authors.affiliation: †Department of Pathology and Molecular Medicine, Queen's University, Kingston, Ontario, Canada, K7P 3N6.
authors.forename: Lindsay S
authors.initials: LS
authors.lastname: Wilson
authors.affiliation: †Department of Pathology and Molecular Medicine, Queen's University, Kingston, Ontario, Canada, K7P 3N6.
authors.forename: Sarah N
authors.initials: SN
authors.lastname: Rampersad
authors.affiliation: *Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada, K7L 3N6.
authors.forename: Fabien
authors.initials: F
authors.lastname: Hubert
authors.affiliation: †Department of Pathology and Molecular Medicine, Queen's University, Kingston, Ontario, Canada, K7P 3N6.
authors.forename: Tammy
authors.initials: T
authors.lastname: Truong
authors.affiliation: *Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada, K7L 3N6.
authors.forename: Milosz
authors.initials: M
authors.lastname: Kaczmarek
authors.affiliation: *Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada, K7L 3N6.
authors.forename: Paulina
authors.initials: P
authors.lastname: Brzezinska
authors.affiliation: *Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada, K7L 3N6.
authors.forename: Silja I
authors.initials: SI
authors.lastname: Freitag
authors.affiliation: *Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada, K7L 3N6.
authors.forename: M Bibiana
authors.initials: MB
authors.lastname: Umana
authors.affiliation: †Department of Pathology and Molecular Medicine, Queen's University, Kingston, Ontario, Canada, K7P 3N6.
authors.forename: Alie
authors.initials: A
authors.lastname: Wudwud
mesh_terms: D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D006801:Humans; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases; D006152:Cyclic GMP