1,25-Dihydroxyvitamin D3 increased beta-adrenergic adenylate cyclase response of fetal rat keratinizing epidermal cells (FRSK cells).

Using fetal rat keratinizing epidermal cells (FRSK), the effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on adenylate cyclase system were investigated. The beta-adrenergic adenylate cyclase response was significantly increased by the stimulation of 1 x 10(-7) M 1,25(OH)2D3. The effect was observed by 6 h and continued for at least 48 h. The 1,25(OH)2D3-induced beta-adrenergic augmentation effect was dose-dependent and the maximal response was observed at a concentration of 1 x 10(-7) M 1,25(OH)2D3. Other adenylate cyclase systems (adenosine, prostaglandin E2 and histamine) were not affected by treatment with 1,25(OH)2D3. The thymidine incorporation in FRSK cells was not significantly affected by 1,25(OH)2D3 treatment. Forskolin-induced cyclic AMP accumulation was significantly increased by 1,25(OH)2D3 treatment. Cholera toxin-induced cyclic AMP accumulation was moderately increased, but this was statistically not significant. Northern blot hybridization showed that none of the mRNAs (the beta 2-adrenergic receptor, the alpha subunits of the stimulatory or inhibitory guanine nucleotide binding proteins, Gs alpha, Gi2 alpha, Gi3 alpha) were significantly altered by 1,25(OH)2D3 treatment. We have already reported that the beta-adrenergic response was increased by dexamethasone and inhibited by retinoids in FRSK cells. The addition of both 1,25(OH)2D3 and dexamethasone to the incubation medium resulted in an additive augmentation. On the other hand, the beta-adrenergic augmentation by the 1,25(OH)2D3 treatment was suppressed by the addition of all trans-retinoic acids. Our results indicate that 1,25(OH)2D3 induces beta-adrenergic augmentation without an alternation of thymidine incorporation of FRSK cells.