1,25-Dihydroxyvitamin D 3 increased β-adrenergic adenylate cyclase response of fetal rat keratinizing epidermal cells (FRSK cells)

Abstract

Using fetal rat keratinizing epidermal cells (FRSK), the effects of 1,25-dihydroxyvitamin D 3 (1,25(OH) 2D 3) on adenylate cyclase system were investigated. The β-adrenergic adenylate cyclase response was significantly increased by the stimulation of 1 × 10 −7 M 1,25(OH) 2D 3. The effect was observed by 6 h and continued for at least 48 h. The 1,25(OH) 2D 3-induced β-adrenergic augmentation effect was dose-dependent and the maximal response was observed at a concentration of 1 × 10 −7 M 1,25(OH) 2D 3. Other adenylate cyclase systems (adenosine, prostaglandin E 2 and histamine) were not affected by treatment with 1,25(OH) 2 D 3. The thymidine incorporation in FRSK cells was not significantly affected by 1,25(OH) 2D 3 treatment. Forskolin-induced cyclic AMP accumulation was significantly increased by 1,25(OH) 2D 3 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 β 2-adrenergic receptor, the α subunits of the stimulatory or inhibitory guanine nucleotide binding proteins, Gsα, Gi2α, Gi3α) were significantly altered by 1,25(OH) 2D 3 treatment. We have already reported that the β-adrenergic response was increased by dexamethasone and inhibited by retinoids in FRSK cells. The addition of both 1,25(OH) 2D 3 and dexamethasone to the incubation medium resulted in an additive augmentation. On the other hand, the β-adrenergic augmentation by the 1,25(OH) 2D 3 treatment was suppressed by the addition of all trans-retinoic acids. Our results indicate that 1,25(OH) 2D 3 induces β-adrenergic augmentation without an alternation of thymidine incorporation of FRSK cells.