1. - Identification and Quantification of PDE Isoenzymes and Subtypes by Molecular Biological Methods

Abstract

This chapter discusses the properties of phosphodiesterases (PDEs) enzymes and the expression patterns of individual isoenzymes in tissues and cells. Cyclic nucleotide PDEs are essential regulators of cyclic nucleotide-dependent signal transduction processes. They terminate the action of the second messengers adenosine 3’:5’-cyclic monophosphate and guanosine 3’:5’-cyclic monophosphate by hydrolyzing them to their respective 5’-nucleoside monophosphates. The PDEs form a biochemically and structurally diverse family of proteins, which has driven a search for therapeutic agents designed to inhibit specific mammalian PDEs. The PDEs fall into two major classes depending on which of two amino acid sequence motifs they possess. The first class contains one of the two genes in Saccharomyces cerevisiae, the “dunce” gene product from Drosophila melanogaster, and all of the identified mammalian PDEs. The second class includes PDEs found in Vibrio fischeri, Saccharomyces cerevisiae, and Candida albicans. Different splice variants from the same gene are numbered in order of discovery. Combining the data from human, bovine, rat, murine, chicken, and canine sources, 18 different PDEs or PDE subunits have been identified.