Dissociation of increases in levels of 3':5'-cyclic AMP and 3':5'-cyclic GMP from induction of ornithine decarboxylase by the tumor promoter 12-O-tetradecanoyl phorbol-13-acetate in mouse epidermis in vivo.

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Abstract
A single application of 17 nmol of 12-O-tetradecanoyl phorbol-13-acetate (TPA) to mouse skin caused a marked (200-400 fold) induction of ornithine decarboxylase (EC 4.1.1.17, L-ornithine carboxy-lyase) activity in mouse epidermal and epidermal-dermal preparations. No change in the basal level of cyclic[c]AMP occurred in epidermal-dermal preparations within 30 min of TPA application. I.p. injection of the .beta.-agonist isoproterenol resulted in a dose dependent accumulation of cAMP 10 min after injection, but caused no induction of ornithine decarboxylase. When isoproterenol was injected 10 min prior to an application of 1.7 or 17 nmol of TPA, the magnitude of ornithine decarboxylase induction was the same as induction with TPA alone. Topical application of 17 nmol of TPA caused no increase in the level of cGMP present in mouse epidermal-dermal preparations 2-20 min after application. I.p. injection of 1.75 .mu.mol of dibutyryl cGMP caused a 6 fold increase in the level of cGMP and/or butyryl derivatives of cGMP in epidermal-dermal preparations within 5 min of injection, and the level remained elevated for at least 20-30 min. Thid dose of dibutyryl cGMP was incapable of inducing ornithine decarboxylase. Injection of dibutyryl cGMP 5 min before application of 1.7 nmol of TPA or 30 min before application of 17 nmol of TPA did not alter the magnitude of the ornithine decarboxylase induction produced by TPA alone. These results suggest that early increases in the total intracellular levels of cAMP or cGMP are not part of the mechanism by which TPA induces ornithine decarboxylase in the epidermis.