MOLECULAR PHARMACOLOGY, 47:1164-1 171 (1995). Regulation of Distinct Cyclic AMP-Specific Phosphodiesterase (Phosphodiesterase Type 4) Isozymes in Human

Many functions of the immune and inflammatory responses are inhibited by agents that increase intracellular levels of cAMP. Recent investigations have revealed that cAMP levels in inflam-matory cells are regulated by cyclic nucleotide phosphodies-terases (PDEs) belonging to the PDE4 family (cAMP-specific PDEs). At least four different genes are known to encode PDE4 isozymes, which are characterized by their selectivity for cAMP over cGMP and their sensitivity to the antidepressant drug rolipram. The aim of our studies was to investigate whether monocytic cells could regulate PDE4 activity and whether cer-tam PDE4 isozymes were expressed preferentially over others. Our results showed that treatment of peripheral blood mono-cytes or closely related Mono Mac 6 cells with dibutyryl-cAMP or other cAMP-elevating agents transiently increased rolipram-sensitive PDE4 activity 2-3-fold, without concomitant increase