PHOSPHATE-TRANSPORT IN PIG PROXIMAL SMALL-INTESTINES DURING POSTNATAL-DEVELOPMENT - LACK OF MODULATION BY CALCITRIOL

The role of calcitriol in the intestinal absorption of inorganic phosp hate (P-i) during postnatal development was studied in newborn [<1 wee k 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 wi th vitamin D-3 (def-D-3). Regardless of age, plasma calcitriol concent rations in def piglets were unphysiologically low (16-21 pg/ml) and di ffered significantly from those in respective con animals (60-69 pg/ml ) and vitamin D-3-treated def piglets (50-56 pg/ml). However, newborn and suckling def piglets had normal Ca (similar to 3.0 mmol/liter) and P-i (similar to 2.8 mmol/liter) plasma levels. Def piglets became hyp ocalcemic (1.9 mmol/liter) and hypophosphatemic (1.9 mmol/liter) betwe en 4-6 weeks pp. Treatment with vitamin D-3 significantly increased pl asma Ca (3.2 mmol/liter) and P-i (2.7 mmol/liter) levels in weaned def animals. Regardless of calcitriol status, net P-i nux rates (active P -i absorption, as determined with the in vitro Ussing-chamber techniqu e) from the upper small intestines was maximal at birth [170-224 nmol/ (cm(2).h)] and decreased by approximately 80% during the brst week of life before remaining constant [30-50 nmol/(cm(2).h)] during the follo wing development. In weaned def piglets, net P-i flux rates were signi ficantly lower by about 80% compared with those in con animals. Treatm ent of def piglets with vitamin D-3 had no effect in newborn and suckl ing animals but reconstituted net P-i flux rates to normal values at w eaning age. Age-dependent and calcitriol-mediated changes in net P-i f lux rates were paralleled by respective maximum velocity values of Na-dependent P-i uptake across the brush border membrane of the enterocy tes (newborn piglets, 1.9-2.2 nmol/(mg protein.10 sec); suckling pigle ts, 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-D-3 animals, respectiv ely). 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 mem brane 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 obser ved. In conclusion, our findings reveal calcitriol-independent mechani sms for active intestinal P-i absorption during the neonatal and suckl ing periods. The onset of the classical calcitriol-dependent mechanism for active intestinal P-i absorption does not occur until weaning.