Studies on the Mechanism of Action of Calciferol: I. BASIC PARAMETERS OF VITAMIN D-MEDIATED CALCIUM TRANSPORT

Abstract

Abstract Intestinal calcium transport was studied in vitro in ileal tissue obtained from vitamin D-deficient (-D) chicks which had received a dietary supplementation (+D) of vitamin D3 (cholecalciferol). When the flux measurements were carried out in both the mucosal → serosal and serosal → mucosal directions, under short-circuit conditions in which the transmural potential difference across the cell could be reduced to zero, it was found that calcium transport in the +D system was an active, cation-oriented process operating against an electropotential gradient. Calcium was not actively transported in the vitamin D-deficient chick. The presence or absence of inorganic phosphate had no effect on calcium flux in either the +D or -D system. Both the flux of 3H2O and 14C-thiourea were identical in the +D and -D systems, which is consistent with the concept that the increased calcium flux due to vitamin D3 treatment is not due to a general permeability difference. A carrier was shown to be present at the brush border side of the intestinal mucosal cells of both vitamin D-treated and -deficient chicks. However, kinetic studies and the differential effects of cold, iodoacetamide, and N-ethylmaleimide on calcium flux suggest that the biochemical properties of the calcium carrier in the +D system have been altered in some manner so as to effect a more efficient uptake of calcium into the cell. Also, the increased calcium flux due to vitamin D3 administration was found to require 40 to 50 hours for optimal development and to be blocked by prior actinomycin D treatment. This supports the hypothesis that the vitamin D-mediated enhancement of calcium transport is achieved indirectly through RNA and protein synthesis, rather than through direct participation of the vitamin.