Effects of 1,25-dihydroxyvitamin D₃ on colonic calcium transport in vitamin D-deficient and normal rats

To determine whether prior vitamin D intake influences the intestinal calcium absorptive action of 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃], we measured in vitro the two unidirectional transepithelial fluxes of calcium across descending colon segments from rats fed either a vitamin D-deficient or normal diet and injected with either 10, 25, or 75 ng of 1,25(OH)₂D₃ or vehicle alone. Vitamin D deficiency abolished net calcium absorption [J(net), -2 ± 2 vs. 12 ± 2 (SE) nmol.cm^-2.h^-1, P < 0.001], and 10 ng of 1,25(OH)₂D₃ raised J(net) to levels found in normal rats. Larger doses (25 and 75 ng) increased J(net) above levels in normal rats given the same dose. In normal rats only 75 ng of 1,25(OH)₂D₃ increased calcium J(net) above vehicle control values (12 ± 2 vs. 38 ± 4 nmol.cm².h^-1, P < 0.001). Circulating 1,25(OH)₂D₃ measured by radioreceptor assay was well correlated with calcium transport. For each dose of 1,25(OH)₂D₃ higher serum 1,25(OH)₂D₃ levels were reached in vitamin D-deficient rats. Only the 75-ng dose increased circulating 1,25(OH)₂D₃ and colonic calcium transport in normal rats. Intravenous [³H]-1,25(OH)₂D₃ disappeared more rapidly from the circulation of normal rats, suggesting that accelerated metabolic degradative processes for 1,25(OH)₂D₃ may be present in normal but not in vitamin D-deficient rats and may account for the lack of a biological response to 1,25(OH)₂D₃ in normal animals.