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 relative ly specifically inhibited by certain agents which augment myocardial c ontractility, promote smooth muscle relaxation and inhibit platelet ag gregation. Adipocyte, platelet, and hepatocyte cGI PDE activities are regulated by cAMP-dependent phosphorylation. Insulin induced phosphory lation/activation of adipocyte and hepatocyte cGI PDEs is thought to b e important in acute regulation of triglyceride and glycogen metabolis m by insulin. Two distinct cGI PDE subfamilies, products of distinct b ut related genes, have been identified. They exhibit the domain struct ure 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 familie s. The expression of cGIP1 and cGIP2 mRNAs differs in different rat ti ssues, 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.