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

Institute of Environmental Medicine, New York University Medical Center, New York, New York 10016

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.

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

¹ This investigation was supported by Grant CA18536 awarded by the National Cancer Institute. NIH, and is part of Center Programs supported by Grant ES00260 from the National Institute of Environmental Health Science; and Grant CA13343 from the National Cancer Institute, NIH. A preliminary report of this work has appeared (10).

² To whom requests for reprints should be addressed.

Received 6/ 4/79. Accepted 10/15/79.