Tumour promoter uncouples beta-adrenergic receptor from adenyl cyclase in mouse epidermis.

Alterations in beta-adrenergic receptor number and function and in the hormonal responsiveness of adenylate cyclase have been observed in transformed cells, and tumours. Phorbol myristate acetate (PMA), a potent tumour promoter in mouse skin, induces a dramatic loss of epidermal responsiveness to catecholamines in vivo, although basal levels of cyclic AMP are not affected. In other work we have shown that PMA treatment does not alter the number or affinity of epidermal beta-receptors, although accumulation of cyclic AMP in response to isoprenaline injection is sharply inhibited. Evidence is presented here that PMA exerts this effect by uncoupling epidermal beta-receptors from adenylate cyclase.