Duodenal calcium binding protein and active calcium transport in rats: are they functionally related?

The effects of calcitriol and a novel calcitriol analogue, 22-oxacalcitriol(OCT) on duodenal Ca transport, calbindin-D9k mRNA, and calbindin-D9kcontent were studied in two animal models reflecting commonhuman pathologies, namely arterial hypertension and chronicrenal failure, as well as in normal rats. The hormone or itsanalogue were administered intraperitoneally to vitamin-D-repleterats. Active Ca transport was increased in both spontaneouslyhypertensive rats (SHR) and in normotensive control WKY rats5 h after calcitriol dosing of either 60 and 600 ng per rat.In WKY, calbindin-D9k content was slightly increased after theinjection of 60 ng calcitriol, but not of 600 ng calcitriolwhereas calbindin-D9k mRNA stayed essentially unchanged. Incontrast, active Ca transport was significantly stimulated afterthe higher dose of 600 ng calcitriol. In SHR, while both dosesof calcitriol increased active Ca transport, they had no stimulatoryeffect on calbindin-D9k mRNA or protein. In chronically uraemicrats, active Ca transport, duo denal calbindin-D9k, and calbindin-D9kmRNA were stimulated after the injection of two subsequent dosesof 300 ng calcitriol per rat. OCT treatment at same dosage ledto a similar stimulation of calbindin-D9k and calbindin-D9kmRNA, but failed to induce an increase in active Ca transport.These results show that the stimulation of intestinal activeCa transport and calbindin-D9k can be entirely dissociated atthe protein synthesis and the mRNA expression level (1) aftercalcitriol administration to normal and hypertensive rats, and(2) after OCT administration to uraemic rats. Even though calbindinmay play a significant role in the regulation of Ca translocationacross the enterocyte, our work provides evidence that intestinalactive Ca transport can be enhanced independently of changesin calbindin-D9k and vice-versa, at least under the presentnon-steady-state conditions.