Biological activity of vitamin D metabolites and analogs: dose-response study of 45Ca transport in an isolated chick duodenum perfusion system.
We have previously reported that vascular perfusion of the normal vitamin D3-replete chick duodenum with physiological amounts of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] increases the unidirectional movement of 45Ca from the lumen to the venous effluent under conditions of normal (0.9 mM) Ca2+ concentrations in both the lumen and vascular perfusate [Endocrinology 115: 1476 1984)]. The purpose of the present study was to determine the dose responsivity of this perfused intestinal calcium transport system for 1,25(OH)2D3 and some structurally related congeners. The dose-response curve was biphasic for all compounds studied; for 1,25(OH)2D3 initial stimulation of transport was detected at only 30 pM [the plasma concentration of 1,25(OH)2D3 is normally 125 pM] while maximal stimulation was 154% above control at a concentration of 650 pM. Above 650 pM 1,25(OH)2D3 the stimulation fell off sharply and transport had returned to basal levels by 1.3 nM. The relative potency of the D homologs tested was respectively 1,25(OH)2D3: 10,000; 1-alpha-hydroxyvitamin D3: 400; 25-hydroxyvitamin D3: 200; 24R,25-dihydroxy-vitamin D3: 137; vitamin D3: 34; 5,6-trans-25-hydroxyvitamin D3: 3. These results establish the usefulness of the perfused intestinal calcium transport system to study the nongenomic actions of 1,25(OH)2D3 on intestinal calcium transport.
D015650:24,25-Dihydroxyvitamin D 3; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002112:Calcifediol / Q000494:pharmacology; D002117:Calcitriol / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D002645:Chickens; D002762:Cholecalciferol / Q000494:pharmacology*; D004100:Dihydroxycholecalciferols / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism*; D006887:Hydroxycholecalciferols / Q000494:pharmacology; D008297:Male; D010477:Perfusion
D002132:Calcium Radioisotopes; D004100:Dihydroxycholecalciferols; D006887:Hydroxycholecalciferols; D002762:Cholecalciferol; D015650:24,25-Dihydroxyvitamin D 3; D002117:Calcitriol; D002112:Calcifediol; D002118:Calcium; C008088:alfacalcidol