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.
D000818:Animals; D002087:Butyrates / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D005260:Female; D007545:Isoproterenol / Q000494:pharmacology*; D051379:Mice; D010704:Phorbols / Q000494:pharmacology*; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D002087:Butyrates; D010704:Phorbols; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D007545:Isoproterenol; D013755:Tetradecanoylphorbol Acetate