Papaverine and Ro 20-1724 Inhibit Cyclic Nucleotide Phosphodiesterase Activity and Increase Cyclic AMP Levels in Psoriatic Epidermis In Vitro

The comparative inhibitory potency of papaverine and Ro 20-1724 (4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone) on cyclic AMP-phosphodiesterase (cAMP-PDE) and cyclic GMP-phosphodiesterase (cGMP-PDE) activities and their effect on the levels of cAMP and cGMP were examined in psoriatic epidermis. At concentrations of 5 × 10-4 M, papaverine inhibited the hydrolysis of both cAMP and cGMP by either the low or high Km psoriatic epidermal PDE nearly 100% (p <.0001) while Ro 20-1724 selectively inhibited the hydrolysis of cAMP 94% (p <.0001) but had no significant effect on cGMP hydrolysis. When keratomed psoriatic epidermal slices were incubated in 5 × 10-4 M papaverine or Ro 20-1724 the tissue levels of cAMP were increased 343% or 1395% respectively (p <.001) with no concomitant change in the levels of cGMP. Selectice inhibition of cAMP hydrolysis by Ro 20-1724 and its greater effectiveness in elevating cAMP levels in slices of psoriatic epidermis Is one explanation for its clinical superiority in treating psoriatic lesions