THE EFFECT OF 24,25-DIHYDROXYVITAMIN-D-3 ON CALCIUM EFFLUX - THE ROLEOF PROTEIN-KINASE-C

24,25 dihydroxyvitamin D-3 (24,25(OH)(2)D-3) is more abundant than 1,2 5(OH)(2)D-3 in the serum. 1,25 dihydroxyvitamin D-3, a potent calciotr opic metabolite of vitamin D, has been shown to induce calcium efflux from bone. This action is probably mediated, in part, by protein kinas e C (PKC). To determine whether 24,25(OH)(2)D-3 affects calcium flux i n bone, neonatal rat calvaria were cultured and the effect of 24,25(OH )(2)D-3 on calcium flux and signal transduction pathways were evaluate d. Compared with a control, 24,25(OH)(2)D-3 (10(8) mol/L) inhibited ba sal net calcium efflux. 24,25 dihydroxyvitamin D-3 also inhibited net calcium efflux induced by the phorbol ester 12 Myristate 13-Acetate (P MA). Translocation of PKC from the membrane to the cytosolic fraction was rapidly and transiently induced by 24,25(OH)(2)D-3. However, 24,25 (OH)(2)D-3 had no effect on cyclic AMP (cAMP) production. In conclusio n, 24,25(OH)(2)D-3, has a direct effect on bone by inhibiting net calc ium efflux which is probably mediated by the deactivation of PKC.