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Phosphate Transport in Pig Proximal Small Intestines during Postnatal Development: Lack of Modulation by Calcitriol¹

Physiologisches Institut, Tierärztliche Hochschule Hannover, D-30173 Hannover, Germany

Address all correspondence and requests for reprints to: PD Dr. B. Schröder, Physiologisches Institut, Tierärztliche Hochschule, Bischofsholer Damm 15/102, D-30173 Hannover, Germany. E-mail: bschroed{at}physiology.tiho-hannover.de

The role of calcitriol in the intestinal absorption of inorganic phosphate (P_i) during postnatal development was studied in newborn [<1 week postpartum (pp)], suckling (3–4 weeks pp), and weaned (>6 weeks pp) control piglets (con) and piglets suffering from inherited calcitriol deficiency (def). In addition, a number of def piglets were treated with vitamin D₃ (def-D₃).

Regardless of age, plasma calcitriol concentrations in def piglets were unphysiologically low (16–21 pg/ml) and differed significantly from those in respective con animals (60–69 pg/ml) and vitamin D₃-treated def piglets (50–56 pg/ml). However, newborn and suckling def piglets had normal Ca (3.0 mmol/liter) and P_i (2.8 mmol/liter) plasma levels. Def piglets became hypocalcemic (1.9 mmol/liter) and hypophosphatemic (1.9 mmol/liter) between 4–6 weeks pp. Treatment with vitamin D₃ significantly increased plasma Ca (3.2 mmol/liter) and P_i (2.7 mmol/liter) levels in weaned def animals.

Regardless of calcitriol status, net P_i flux rates (active P_i absorption, as determined with the in vitro Ussing-chamber technique) from the upper small intestines was maximal at birth [170–224 nmol/(cm²·h)] and decreased by approximately 80% during the first week of life before remaining constant [30–50 nmol/(cm²·h)] during the following development. In weaned def piglets, net P_i flux rates were significantly lower by about 80% compared with those in con animals. Treatment of def piglets with vitamin D₃ had no effect in newborn and suckling animals but reconstituted net P_i flux rates to normal values at weaning age. Age-dependent and calcitriol-mediated changes in net P_i flux rates were paralleled by respective maximum velocity values of Na⁺-dependent P_i uptake across the brush border membrane of the enterocytes (newborn piglets, 1.9–2.2 nmol/(mg protein·10 sec); suckling piglets, 0.4–0.6 nmol/(mg protein·10 sec); weaned piglets, 0.7, 0.3, and 0.7 nmol/(mg protein·10 sec) in con, def, and def-D₃ animals, respectively). These findings suggest that the apical P_i uptake represents the major rate-limiting step of the overall transepithelial P_i transport. At weaning, Na⁺/P_i transport across the intestinal brush-border membrane is clearly stimulated by calcitriol, but no significant effects of age or calcitriol on the K_m values (0.5–0.7 mmol/liter) were observed.

In conclusion, our findings reveal calcitriol-independent mechanisms for active intestinal P_i absorption during the neonatal and suckling periods. The onset of the classical calcitriol-dependent mechanism for active intestinal P_i absorption does not occur until weaning.

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