TYPE-III CGMP-INHIBITED CYCLIC-NUCLEOTIDE PHOSPHODIESTERASES (PDE-3 GENE FAMILY)

Seven different but related cyclic nucleotide phosphodiesterase (PDE) gene families have been identified. Type III cGMP-inhibited (cGI) PDEs, the PDE3 gene family, are found in many tissues. cGI PDEs exhibit a high affinity for both cAMP and cGMP, and are selectively and relatively specifically inhibited by certain agents which augment myocardial contractility, promote smooth muscle relaxation and inhibit platelet aggregation. Adipocyte, platelet, and hepatocyte cGI PDE activities are regulated by cAMP-dependent phosphorylation. Insulin induced phosphorylation/activation of adipocyte and hepatocyte cGI PDEs is thought to be important in acute regulation of triglyceride and glycogen metabolism by insulin. Two distinct cGI PDE subfamilies, products of distinct but related genes, have been identified. They exhibit the domain structure common to PDEs with a carboxyterminal region, conserved catalytic domain and divergent regulatory domain. In their catalytic domains cGI PDEs contain a 44 amino acid insertion not found in other PDE families. The expression of cGIP1 and cGIP2 mRNAs differs in different rat tissues, suggesting distinct functions for the two cGI PDE subfamilies, i.e., cGIP1 in adipose tissue, liver, testis and cGIP2 in myocardium, platelets and smooth muscle.