The effects of alpha and beta adrenergic agonists and cyclic adenosine 3':5'-monophosphate on epidermal metabolism.

Continuously regenerating stratified squamous epithelia form an interesting model for examining mechanisms controlling the balance between rates of cell formation and cell maturation and death. In vitro assays of rates of glycolysis and amino acid incorporation of epidermal sheets free from dermal contamination were used to examine rates of metabolism in both normal and hyperplastic epidermis after treatment with various adrenergic agonists and cAMP. Epinephrine and isoproterenol over the concentration range of 1 x 10(-9) to 1 x 10(-5) M depressed the rates of glycolysis and amino acid incorporation in normal epidermis. Dibutyryl cyclic AMP produced a 73 to 78% depression in metabolic activity and its action was enhanced by the addition of theophylline. The alpha adrenergic agonist norepinephrine produced similar reductions. When epidermal samples were treated with hexadecane to induce a mild hyperplasia, depressant effects of isoproterenol and epinephrine were lost, but dibutyryl cyclic AMP and norepinephrine still reduced metabolic activity. The results suggest that adrenergic agents and their putative second messenger cAMP cause reductions in epidermal metabolic activity, an effect similar to their effects on cell proliferation, and that increased rates of proliferation are associated with loss of beta adrenergic responsiveness of the epidermis.