Abstract
We studied the effect of activation of protein kinase C (PKC) by a phorbol ester on cAMP accumulation in fetal rat osteoblasts. Activation of PKC by phorbol 12โmyristate 13โacetate (PMA) caused a potentiation of cAMP accumulation induced by parathyroid hormone (PTH), forskolin, and cholera toxin. The results suggest that the potentiating effect of PMA on PTHโinduced cAMP accumulation was not due to an effect on the PTHโreceptor nor to an effect on cAMP degradation, as the effect of PMA persisted in the presence of a phosphodiesterase inhibitor. Pretreatment of the cells with pertussis toxin did not prevent the action of PMA, indicating that PMA does not act via the inhibitory Gโprotein. PMA had a biphasic effect on prostaglandin E~2~ (PGE~2~)โinduced cAMP accumulation; i.e., at concentrations โฉพ 10^โ6^ M, PMA potentiated the PGE~2~โinduced cAMP response but PMA attenuated cAMP accumulation induced by concentrations of PGE~2~ โฉฝ 5.10^โ7^ M. From our data we conclude that PKC can interact with a stimulated cAMP pathway in a stimulatory and inhibitory manner. Potentiation of cAMP accumulation is probably due to modification of the adenylate cyclase complex, whereas attenuation of stimulated cAMP accumulation appears to be due to an effect on a different site of the cAMP generating pathway, which may be specific to PGE~2~โinduced cAMP accumulation.