Retinoid-induced beta-adrenergic inhibitory effect associated with increased thymidine incorporation of fetal rat keratinizing epidermal cells (FRSK cells).

Using fetal rat keratinizing epidermal cells (FRSK cells) we investigated the effects of retinoids on the cyclic AMP system. The beta-adrenergic adenylate cyclase response was significantly decreased by the treatment of cells with 1 x 10(-6) M Ro 10-1670. The effect was observed by 12 h and remained for at least 48 h. The decreased beta-adrenergic response was accompanied by increased adenosine- and forskolin-induced cyclic AMP accumulations. Thymidine incorporation of FRSK cells was also increased by the retinoid treatment. Northern blot hybridization showed that none of the messages (the beta2-adrenergic receptor, the stimulatory guanine nucleotide binding protein (Gs-alpha), or the inhibitory guanine nucleotide binding proteins (Gi-2 alpha, Gi-3 alpha)) were significantly altered by the retinoid treatment. We have already reported that the beta-adrenergic response as well as the beta2-adrenergic receptor mRNA is increased by the dexamethasone treatment of FRSK cells. The addition of both Ro 10-1670 and dexamethasone in the incubation medium resulted in the loss of the beta-adrenergic augmentation effect by dexamethasone. These results indicate that retinoids decrease the beta-adrenergic response and increase the thymidine incorporation of FRSK cells. This is contrary to the previous results using pig epidermal organ culture system.