Dibutyryl Cyclic AMP Inhibition of Epidermal Cell Division

Dibutyryl adenosine 3′,5′-monophosphate (cyclic AMP), but not sodium butyrate or adenosine 5′-monophosphate (5′-AMP) produced a dose-dependent epidermal mitotic inhibition. Previously we showed that isoproterenol inhibits epidermal mitosis, stimulates adenyl cyclase activity in broken epidermal cells, and stimulates cyclic AMP formation in intact epidermis. This data and results from the present study strongly suggest that cyclic AMP is one and possibly a major mediator of epidermal mitotic control. Our findings together with recent evidence that cyclic AMP inhibits cell growth rate while promoting differentiation in cultured cells suggests the following: (1) the rate of epidermal proliferation may be inversely proportional to the intraepidermal cyclic AMP level; (2) the 12-fold accelerated proliferation rate and glycogen accumulation of psoriatic epidermis might be due to low intraepidermal cyclic AMP concentrations.