Antipsoriatic and antimetabolic agents as stimulators of the beta-adrenergic adenylate cyclase response of epidermis

Using pig skin organ culture in vitro, we compared the effects of antipsoriatic and anti-metabolic agents on the beta-adrenergic response of epidermis. After a 24-h incubation with these chemicals, the beta-adrenergic response of epidermis was shown to be increased to various degrees. Among the chemicals, colchicine, actinomycin D, and puromycin had the most marked effect, and were followed by Ro 10–1670 and hydrocortisone, and then by anthralin, cycloheximide and N-5’(N-(3,4-dimethyloxycinnamoyl) anthranilic acid). Methotrexate and hydroxyurea apparently had no (or rather decreasing) effects on the beta-adrenergic response of epidermis. After the same treatment in vitro, thymidine incorporation of epidermal keratinocytes was compared. In the latter system, the inhibitory effects of puromycin, cycloheximide and actinomycin D were most marked, and were followed by those of colchicine and Ro ro-1670, and then hydrocortisone and anthralin. n-s' had no effect and hydroxyurea increased thymidine incorporation of keratinocytes. Our data indicate that most (but not all) anti-psoriatic agents do augment the beta-adrenergic response of epidermis, which might be associated with the clinical efficacy of these agents in psoriasis where a defective beta-adrenergic response is well documented. The augmentation effects of these chemicals, however, did not correlate with their inhibitory effects on keratinocyte proliferation, at least in the thymidine incorporation system in epidermal keratinocytes in vitro.