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

Abstract The effects of calcitriol and a novel calcitriol analogue, 22-oxacalcitriol (OCT) on duodenal Ca transport, calbindin-D9k mRNA, and calbindin-D9k content were studied in two animal models reflecting common human pathologies, namely arterial hypertension and chronic renal failure, as well as in normal rats. The hormone or its analogue were administered intraperitoneally to vitamin-D-replete rats. Active Ca transport was increased in both spontaneously hypertensive rats (SHR) and in normotensive control WKY rats 5 h after calcitriol dosing of either 60 and 600 ng per rat. In WKY, calbindin-D9k content was slightly increased after the injection of 60 ng calcitriol, but not of 600 ng calcitriol whereas calbindin-D9k mRNA stayed essentially unchanged. In contrast, active Ca transport was significantly stimulated after the higher dose of 600 ng calcitriol. In SHR, while both doses of calcitriol increased active Ca transport, they had no stimulatory effect on calbindin-D9k mRNA or protein. In chronically uraemic rats, active Ca transport, duo denal calbindin-D9k, and calbindin-D9k mRNA were stimulated after the injection of two subsequent doses of 300 ng calcitriol per rat. OCT treatment at same dosage led to a similar stimulation of calbindin-D9k and calbindin-D9k mRNA, but failed to induce an increase in active Ca transport. These results show that the stimulation of intestinal active Ca transport and calbindin-D9k can be entirely dissociated at the protein synthesis and the mRNA expression level (1) after calcitriol administration to normal and hypertensive rats, and (2) after OCT administration to uraemic rats. Even though calbindin may play a significant role in the regulation of Ca translocation across the enterocyte, our work provides evidence that intestinal active Ca transport can be enhanced independently of changes in calbindin-D9k and vice-versa, at least under the present non-steady-state conditions.