Regulation of Na-dependent phosphate influx across the mucosal border of duodenum by 1,25-dihydroxycholecalciferol.
Animals teated with disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP), at doses which decrease the renal production and/or the plasma levels of 1,25-dihydroxycholecalciferol [1,25(OH)2D3], display a reduced net absorption of phosphate. In this study we investigated whether EHDP-treatment and administration of 1,25(OH)2D3 to EHDP-treated animals affected the phosphate influx across the mucosal border of rabbit duodenum. The initial rate of phosphate influx into mucosal cells was measured in isolated intestine. In control, untreated rabbits, the phosphate influx shows a saturable, Na-dependent component and a diffusional, Na-independent uptake. In tissue from rabbits treated for 3 days with EHDP, the phosphate influx was found to be strongly reduced. EHDP-treatment decreased the Na-dependent, carrier mediated phosphate influx in duodenum. Administration of 1,25(OH)2D3 to EHDP-treated animals reversed the reduced phosphate influx. These effects were mainly apparent through changes in the J(mc)(max) of the phosphate influx, which was decreased from 211 +/- 38.7 nmol/cm2h in controls to 42.1 +/- 18.1 nmole/cm2 h in the EHDP-treated group and increased to 413 +/- 43.6 nmole/cm2 h by 1,25(OH)2D3. The treatment did not appear to affect the diffusional, Na-independent phosphate influx. EHDP-treatment did not affect the influx of alanine in this segment suggesting that EHDP-treatment affects only 1,25(OH)2D3-dependent transport mechanisms. The results suggest that 1,25(OH)2D3 modulates the number of carrier sites available at the mucosal membrane for Na-dependent phosphate entry.
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002117:Calcitriol; D004100:Dihydroxycholecalciferols / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000378:metabolism*; D006887:Hydroxycholecalciferols / Q000494:pharmacology*; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism*; D008871:Microvilli / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism*; D011817:Rabbits; D012964:Sodium / Q000378:metabolism
D004100:Dihydroxycholecalciferols; D006887:Hydroxycholecalciferols; D010710:Phosphates; D012964:Sodium; D002117:Calcitriol