Antagonism between phorbol myristate acetate and butyric acid on isoproterenol elevation of cyclic adenosine 3':5'-monophosphate and their effects on beta-adrenergic receptors in mouse epidermis.

Butyric acid enhanced adenosine 3':5'-monophosphate accumulation in both untreated and isoproterenol-stimulated epidermis. A single treatment with 17 nmol of the potent tumor promoter, phorbol myristate acetate (PMA), inhibited cyclic adenosine 3':5'-monophosphate accumulation in isoproterenol and in butyric acid-stimulated epidermis. beta-Adrenergic receptors in mouse epidermis were measured by the binding of L-[3H]dihydroalprenolol. The apparent dissociation constant was 52 nM, and 33 fmol L-[3H]dihydroalprenolol were bound per microgram DNA. An increase in receptors was induced in vivo with 200 nmol butyric acid. The induction exhibited a 2-fold maximum at 72 hr and a decline to control values at 120 hr. PMA had no effect on the number or availability of the beta-receptors, nor did it affect the butyric acid induction. The biochemical antagonism between PMA and butyric acid on the beta-adrenergic responsiveness of mouse epidermis may be a result of opposing actions on the coupling of beta-receptors to adenyl cyclase. The alteration in the function of membrane receptors involved in cell metabolism may be responsible for some of the biological effects of PMA and other promoters.