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Arachidonic acid- or collagen-induced aggregation was accompanied by a progressive elevation in the level of cyclic GMP in washed human platelets with no significant alteration in the concentration of cyclic AMP. The extent of the increase in cyclic GMP was proportional to the concentration of arachidonic acid added. Enhanced accumulation of cyclic GMP produced by arachidonic or collagen was prevented by prior exposure of platelets to aspirin or indomethacin. Prostaglandin endoperoxide G2 caused platelet aggregation and an increase in cyclic GMP concentration; neither event was blocked by prostaglandin synthesis inhibitors. These results indicate that the generation of prostaglandin endoperoxides is a step in the sequence of events in platelet aggregation leading to the enhanced accumulation of cyclic GMP.

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 with normal epidermis. Arachidonic acid or HETE (5 to 50 microM) 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 the biosynthetic capacity to generate cGMP is markedly increased in involved epidermis from psoriatics because of a markedly increased specific activity of guanylate cyclase and an alteration in a property of this enzyme activity which renders it stimulable by fatty acids reported to accumulate in this lesion.