MOLECULAR-CLONING AND FUNCTIONAL EXPRESSION IN YEAST OF A HUMAN CAMP-SPECIFIC PHOSPHODIESTERASE SUBTYPE (PDE IV-C)

We have recently reported increased survival of dopaminergic substanti a nigra neurons by inhibition of phosphodiesterase type IV enzymes. As a first step to unravel the involvement of PDE IV subtypes in this pr ocess, we isolated phosphodiesterase type IV cDNAs from human substant ia nigra. One isolated partial cDNA clone was most homologous to the p artially cloned rat and human PDE IV-C isogene. Distribution analysis revealed that the enzyme is expressed in various tissues but not in ce lls of the immune system. Isolation of the full-length human PDE IV-C isogene cDNA and expression in a PDE-deficient yeast strain resulted i n functional complementation of the yeast heat shock response. Inhibit ion of the enzymatic activity by rolipram characterized this enzyme as a typical type IV phosphodiesterase.