Phosphodiesterase 8A, cAMP-specific

Phosphodiesterase 8A (PDE8A) is a 3′,5′-cyclic-nucleotide phosphodiesterase that specifically catalyses the hydrolysis of cAMP to AMP. PDE8A is one of the two isoenzymes of the PDE8 family, the other being PDE8B. These two highly similar proteins have several common features that distinguish them from other cAMP-specific PDEs: they have very high affinity for the substrate cAMP; they are insensitive to the non-specific PDE inhibitor IBMX. They contain a PAS (Per, Arnt and Sim) and a REC (receiver) domain, both of which are observed in many signal transduction proteins. The possible function(s) of the PAS domain in PDE8 is still unknown. PDE8A mRNA is not expressed in all tissues but has been detected in several and is highest in testis, spleen, small intestine, heart, ovary, colon and kidney. Until early 2009, the lack of specific small-molecule inhibitors slowed the study of the physiological relevance of PDE8A; thus to date many aspects of this PDE's functions (that is, whether it is activated or regulated during certain cellular process) remain in large part unknown. So far, functions for PDE8A have been described in Leydig cells, where lack of PDE8A causes increased testosterone production in response to luteinizing hormone; T cells, where it seems to be induced during T cell activation and may control chemotaxis; and cardiocytes, where it seems to regulate calcium handling