Reduced epidermal cyclic AMP accumulation following prostaglandin stimulation: Its possible role in the pathophysiology of psoriasis

Abstract

Since prostaglandins are known to be one of the modulators of cyclic AMP, a study of the role of prostaglandins and their relation to the regulation of the nucleotide in psoriasis was initiated. Guinea-pig epidermal preparations were incubated with prostaglandins (PGs) in the presence of theophylline. PGE1 increased cyclic AMP levels 3.5-fold whereas a 2-fold increase was seen with PGE2 and PGA1. The increase in cyclic AMP accumulation was linear with increasing concentration of PGE1, from 10(-11) to 10(-5) M. PGE1 significantly increased cyclic AMP in psoriatic epidermis in vitro; however, the stimulation of cyclic AMP accumulation was significantly less in involved epidermis as compared with uninvolved tissue. The specificity of this stimulation, its occurrence at physiologic levels, and the decreased responsiveness of the cyclic AMP system in psoriatic epidermis to PGE1 stimulation suggest that the altered response of epidermis to PGs may be one of the factors in the pathophysiology of psoriasis.