Phosphodiesterase

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Phosphodiesterase (PDE) is a group of enzymes that degrade the second messenger molecules: cyclic nucleotides cAMP and cGMP. They regulate the localization, duration, and amplitude of cyclic nucleotide signaling within subcellular domains. PDEs are therefore important regulators of signal transduction mediated by these second messenger molecules.

The PDE superfamily of enzymes are classified into 11 families, namely PDE1-PDE11, in mammals. The classification is based on:

amino acid sequences
substrate specificities
regulatory properties
pharmacological properties
tissue distribution

PDE3 is sometimes refered to as cGMP inhibited phosphodiesterase.

The nomenclature for PDE indicates PDE family by an Arabic numeral that is followed by a capital letter to denote the gene within a family. A second Arabic numeral indicates the splice variant derived from a single gene (e.g., PDE1C3: family 1, gene C, splicing variant 3) <ref>Conti M. (2000) Phosphodiesterases and Cyclic Nucleotide Signaling in Endocrine Cells Molecular Endocrinology 14 (9): 1317-1327.</ref>

PDE enzymes are often targets for pharmalogical inhibition due to their unique tissue distribution, structural and functional properties. Inhibitors of PDE can prolong or enhance the effects of physiological processes mediated by cAMP or cGMP by inhibition of their degradation by PDE. Sildenafil (Viagra) is an inhibitor of cGMP specific phosphodiesterase type 5, which enhances the vasodilatory effects of cGMP in the corpus cavernosum and is used to treat erectile dysfunction. PDE inhibitors have been identified as new potential therapeutics in areas such as pulmonary arterial hypertension, coronary heart disease, dementia, depression and schizophrenia.

[edit] References

Beavo JA, Brunton LL. Cyclic nucleotide research -- still expanding after half a century. Nat Rev Mol Cell Biol. 2002 Sep;3(9):710-8.

Cohen AH, Hanson K, Morris K, Fouty B, McMurty IF, Clarke W, Rodman DM. Inhibition of cyclic 3'-5'-guanosine monophosphate-specific phosphodiesterase selectively vasodilates the pulmonary circulation in chronically hypoxic rats. J Clin Invest. 1996 Jan 1;97(1):172-9

Jeon YH, Heo YS, Kim CM, Hyun YL, Lee TG, Ro S, Cho JM. Phosphodiesterase: overview of protein structures, potential therapeutic applications and recent progress in drug development. Cell Mol Life Sci. 2005 Jun;62(11):1198-220. Review.