Antagonism between Phorbol Myristate Acetate and Butyric Acid on Isoproterenol Elevation of Cyclic Adenosine 3′:5′-Monophosphate and Their Effects on β-Adrenergic Receptors in Mouse Epidermis¹

Butyric acid enhanced cyclic 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.

β-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 µg 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 β-receptors, nor did it affect the butyric acid induction. The biochemical antagonism between PMA and butyric acid on the β-adrenergic responsiveness of mouse epidermis may be a result of opposing actions on the coupling of β-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.