Hypercalcemia inhibits the rapid stimulatory effect on calcium transport in perfused duodena from normal chicks mediated in vitro by 1,25-dihydroxyvitamin D3.

We have previously reported that vascular perfusion of normal vitamin D3-replete chick duodena with physiological amounts of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] increases the movement of 45Ca2+ from the lumen to the venous effluent within 14 min under conditions of normal Ca2+ (0.9 mM) concentration in both the lumen and vascular perfusate. The present studies were designed to further explore details of this rapid 1,25-(OH)2D3 effect as a function of seco-steroid concentration and under conditions where the free Ca2+ concentrations in the perfusate were varied from 0.54-1.26 mM. Concentrations of 1,25-(OH)2D3 in the vascular perfusate ranging from 30-650 pM elicited an increasing stimulation of Ca transport, as judged by 45Ca levels in the venous effluent. At 0.98-6.5 nM 1,25-(OH)2D3, progressive inhibition of Ca transport was observed, yielding a biphasic dose-response curve. The optimal concentration of 650 pM 1,25-(OH)2D3 was used in subsequent experiments designed to study the effects of vascular Ca2+ levels on 45Ca transport mediated by the seco-steroid. The basal Ca2+ transport ratio, in the absence of 1,25-(OH)2D3, did not change when the divalent cation of the vascular perfusate was varied over the range 0.54-1.26 mM free calcium. However, the effect of 1,25-(OH)2D3 on 45Ca2+ transport was completely abolished in the group treated with 1.21 mM Ca2+ in the perfusate, but not in the groups treated with concentrations less than 1.17 mM Ca2+. These results suggest that the rapid intestinal calcium transport response to 1,25-(OH)2D3 may be modulated locally in part by the prevailing ionized Ca concentration of the vascular perfusate.