Papaverine and Ro 20-1724 Inhibit Cyclic Nucleotide Phosphodiesterase Activity and Increase Cyclic AMP Levels in Psoriatic Epidermis In Vitro
1978; Elsevier BV; Volume: 71; Issue: 2 Linguagem: Inglês
10.1111/1523-1747.ep12546928
ISSN1523-1747
AutoresLouis J. Rusin, Eric J. Duell, John J. Voorhees,
Tópico(s)Phosphodiesterase function and regulation
ResumoThe 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 X 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 less than .0001) while Ro 20-1724 selectively inhibited the hydrolysis of cAMP 94% (p less than .0001) but had no significant effect on cGMP hydrolysis. When keratomed psoriatic epidermal slices were incubated in 5 X 10(-4) M papaverine or Ro 20-1724 the tissue levels of cAMP were increased 343% or 1395% respectively (p less than .001) with no concomitant change in the levels of cGMP. Selective 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.
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