Potentiation of prostaglandin E1-stimulated cAMP formation by 12-O-tetradecanoylphorbol-13-acetate in BALB/c mouse 3T3 cells.

Prostaglandin E1 (PGE1: 0.1-100 microM), forskolin (0.1-100 microM), and cholera toxin (20 ng/ml) stimulated cAMP formation of BALB/c 3T3 cells. The pretreatment of the cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) enhanced PGE1 (10 microM)-stimulated cAMP formation in a concentration- and a time-dependent manner. If the cells were pretreated with TPA (0.1 microM) for only 1 hr, the above augmentation was not observed. Maximal enhancement was observed by pretreatment of the cells for 5 hr with 0.1 microM TPA. Basal cAMP formation was not affected by TPA pretreatment. Other tumor promoters, such as teleocidin and mezerein, showed a potentiating effect similar to that of TPA on the PGE1-stimulated cAMP formation. However, phorbol which is not a tumor promoter, failed to potentiate PGE1 action significantly. These results suggest that the above TPA action may share some common mechanisms with the tumor-promoting action of this agent. On the other hand, the forskolin- and cholera toxin-stimulated cAMP formations were not changed by pretreatment of the cells with TPA. Therefore, our results indicate that the potentiating action of TPA on PGE1-stimulated cAMP formation in 3T3 cells is not due to the activation of the catalytic unit or the stimulatory guanine nucleotide binding protein (Ns) of adenylate cyclase (AC) system by this agent. It is highly likely that TPA induces some alterations on PGE1 receptors or on PGE1 receptor-Ns coupling systems and consequently induces an augmentation of PGE1-stimulated cellular cAMP response.