ABSTRACT
Enzymes of the family of cyclic nucleotide phosphodiesterases are known to catalyze the breakdown of cyclic adenosine monophosphate (cAMP) and Cyclic guanosine monophosphate. Phosphodiesterases consist of three different regions: A C-terminal conserved catalytic domain, an N-terminal splicing region and a regulatory domain. Crystal structures of phosphodiesterases with the products of the hydrolysis show interactions between the phosphate oxygen and the metal ions. Since the approval of Viagra in May 1998 some inhibitors of phosphodiesterases achieved great success from a clinical and financial point of view. Sildenafil and tadalafil are also tested in various clinical trials for a wide array of different fields of indications such as schizophrenia, diabetes and lung diseases. Consequently administration of PDE4-specific inhibitors has proven to reduce lung inflammation, airway hyperresponsiveness, leukocyte infiltration and cytokine production in the lung. cAMP also lowers the capacity of leukocytes toward bacteria viruses fungi and eukaryotic parasites.
