Apparent nonnuclear regulation of intestinal phosphate transport: effects of 1,25-dihydroxyvitamin D3,24,25-dihydroxyvitamin D3, and 25-hydroxyvitamin D3.

The steroid hormone 1,25-(OH)2D3 modulates a number of cellular functions through nonnuclear pathways, particularly the stimulation of intestinal calcium transport (transcaltachia). The present studies determined whether 1,25-(OH)2D3 rapidly enhanced phosphate transport in the perfused duodenal loop of normal chicks. Vascular perfusion with 65 pM 1,25-(OH)2D3 significantly stimulated the appearance of 33P 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 33P in the venous effluent. Vascular perfusion with a range of 1,25-(OH)2D3 concentrations yielded an apparent biphasic dose-response curve. Two additional vitamin D metabolites, 24,25(OH)2D3 and 25(OH)D3, which initiate transcaltachia, were tested for their effect on phosphate transport. Neither 6.5 nM 24,25(OH)2D3 nor 100 nM 25(OH)D3 stimulated 33P movement from the lumen to the venous effluent. When duodena were vascularly perfused with 65 pM 1,25-(OH)2D3 and either 6.5 nM 24,25(OH)2D3 or 100 nM 25(OH)D3, enhanced phosphate transport was attentuated or abolished. Phosphate transport was also analyzed at metabolite levels 5-fold lower or higher than those in normal chicks. For 24,25(OH)2D3, 1.3 nM metabolite did not augment phosphate transport, although stimulation did occur at 32.5 nM steroid (180 +/- 0.2% of controls). For 25(OH)D3, 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)2D3, or 6.5 nM 24,25(OH)2D3. In contrast, vascular perfusion with 100 nM 25(OH)D3 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)2D3, 6.5 nM 24,25(OH)2D3, and 100 nM 25(OH)D3, initiate transcaltachia in the presence of lumenal P(i), the absence of the anion abolished the stimulatory effects of 1,25-(OH)2D3 and 24,25(OH)2D3 on calcium transport but not those induced by 25(OH)D3. These data suggest a complex regulation of both calcium and phosphate transport based on relative levels of circulating vitamin D metabolites as well as the ionic content of the lumen.