Cyclic GMP Metabolism in Psoriasis: Activation of Soluble Epidermal Guanylate Cyclase by Arachidonic Acid and 12-Hydroxy-5,8,10,14-Eicosatetraenoic Acid

Soluble guanylate cyclase activity was measured in normal and psoriatic human epidermis. The specific activity of guanylate cyclase was determined to be increased 10-fold and 3-fold in involved and uninvolved epidermis of psoriatics, respectively, compared to normal epidermis. Arachidonic acid (5 to 100 μM) or 12-hydroxy-5,8,10,14-eicosatetraenoic acid (HETE) (5 to 50 μM) stimulated guanylate cyclase activity from involved epidermis 2- to 3-fold and from uninvolved epidermis up to 2-fold, but these fatty acids had no effect on the activity of this cyclase from normal epidermis. These results indicate that there is an increase in the cGMP biosynthetic capacity of involved epidermis from psoriatics that derives from a markedly increased specific activity of guanylate cyclase and an alteration in a property of this enzyme activity which renders it responsive to fatty acids reported to accumulate in this lesion. These observations are consistent with the report that an elevated steady-state level of cGMP is one of the consequences of the strikingly altered metabolism of cGMP in psoriatic epidermis