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

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  • 1 January 1980
    • journal article
    • research article
    • Vol. 40  (2) , 240-244
Abstract
Butyric acid enhanced cyclic[c]AMP accumulation in untreated and isoproterenol-stimulated epidermis. A single treatment with 17 nmol of the potent tumor promoter, phorbol myristate acetate (PMA), inhibited cAMP 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 Kd was 52 nM, and 33 f[femto]mol L-[3H]dihydroalprenolol were bound per .mu.g DNA. An increase in receptors was induced in vivo with 200 nmol butyric acid. The induction exhibited a 2-fold maximum at 72 h and a decline to control values at 120 h. 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.