Endogenous inhibition of cyclic nucleotide phosphodiesterase in cultured human epithelial cells

We have identified an endogenous inhibitor of cyclic nucleotide phosphodiesterase (PDE) activity in cultured human epithelial cells. The inhibitor was non-dialyzable, inactivated by trypsin and boiling, but stable to a 60° C, 30 min. treatment. Separation of inhibitor from PDE was achieved by blue dextran affinity chromatography. PDE was eluted from this column by EDTA, while the inhibitor remained bound and was subsequently eluted with buffer containing cyclic GMP. The inhibitor was active against PDE from several sources including both Ca⁺⁺ dependent and Ca⁺⁺ independent forms from bovine brain and retina respectively. These characteristics differentiate the PDE inhibitor from human epithelial cells from those previously described from various bovine tissues.