2. - Analysis of PDE Isoenzyme Profiles in Cells and Tissues by Pharmacological Methods

Abstract

This chapter gives a synoptic view of analysis of phosphodiesterase (PDE) isoenzyme activities in cells and tissues. PDE inhibitors have been proposed as drugs for a variety of diseases (asthma, vascular disease, diabetes, AIDS, rheumatic disease, and multiple sclerosis). To target a specific disease and to limit adverse events caused by a PDE inhibitor, the ubiquity of PDE and the heterogeneity of its isoenzymes both require and facilitate the development of cell-specific PDE inhibitors. To meet these challenges it is essential to establish PDE isoenzyme profiles of target cells and of those cells that could potentially contribute to adverse events. In this chapter, PDE isoenzyme activity profiles obtained by pharmacological methods have been reviewed. These pharmacological methods used selective inhibitors and activators of PDE isoenzyme families to establish PDE isoenzyme family activity profiles. It is concluded that PDE4/PDE3 inhibitors are beneficial in inflammatory diseases. However, neuronal cells also contain PDE4 activity and this finding may explain why PDE4 inhibitors frequently induce CNS-related adverse events (vomiting, nausea). A combined approach of PDE activity measurements, detection of PDE proteins with subtype- and splice variant-specific monoclonal antibodies, and detection of PDE mRNA with RT-PCR as described in this volume represents the most powerful approach for characterizing PDE isoenzymes in cells and tissues.