Apparent nonnuclear regulation of intestinal phosphate transport: Effects of 1,25-dihydroxyvitamin D-3, 24,25-dihydroxyvitamin D-3, and 25-hydroxyvitamin D-3

The steroid hormone 1,25-(OH)(2)D-3 modulates a number of cellular functions through nonnuclear pathways, particularly the stimulation of intestinal calcium transport (transcaltaehia). The present studies determined whether 1,25-(OH)(2)D-3 rapidly enhanced phosphate transport in the perfused duodenal loop of normal chicks. Vascular perfusion with 65 pM 1,25-(OH)(2)D-3 significantly stimulated the appearance of P-33 in the venous effluent within 2-8 min, reaching an average of 160% of control levels by 40 min. Lumenal perfusion with hormone failed to augment levels of P-33 in the venous effluent. Vascular perfusion with a range of 1,25-(OH)(2)D-3 concentrations yielded an apparent biphasic dose-response curve. Two additional vitamin D metabolites, 24,35(OH)(2)D-3 and 25(OH)D-3, which initiate transcaltachia, were tested for their effect on phosphate transport. Neither 6.5 nM 24,25(OH)(2)D-3 nor 100 nM 25(OH)D-3 stimulated P-33 movement from the lumen to the venous effluent. When duodena were vascularly perfused with 65 pM 1,25-(OH)(2)D-3 and either 6.5 nM 24,25(OH)(2)D-3 or 100 nM 25(OH)D-3, enhanced phosphate transport was attentuated ol abolished. Phosphatetransport was also analyzed at metabolite levels 5-fold lower or higher than those in normal chicks. For 24,25(OH)(2)D-3, 1.3 nM metabolite did nut augment phosphate transport, although stimulation did occur at 32.5 nM steroid (180 +/- 0.2% of controls). For 25(OH)D-3, no stimulation was observed at 500 nM metabolite, whereas 20 nM steroid resulted in transport that was 160 +/- 0.14% of controls. The presence or absence of lumenal Ca2+ did not influence phosphate transport in duodena vascularly perfused with control medium, 65 pM 1,25-(OH)(2)D-3, or 6.5 nM 24,25(OH)(2)D-3. In contrast, vascular perfusion with 100 nM 25(OH)D-3 stimulated phosphate transport when lumenal Ca2+ was present but not when it was absent. The influence of lumenal P-i on transcaltachia was then studied. Although 65 pM 1,25-(OH)(2)D-3, 6.5 nM 24,25(OH)(2)D-3, and 100 nM 25(OH)D-3 initiate transcaltachia in the presence of lumenal P-i, the absence of the anion abolished the stimulatory effects of 1,25-(OH)(2)D-3 and 24,25(OH)(2)D-3 on calcium transport but not those induced, by 25(OH)D-3. These data suggest a complex regulation uf both calcium and phosphate transport based an relative levels of circulating vitamin D metabolites as well as the ionic content of the lumen.