DUODENAL CALCIUM-BINDING PROTEIN AND ACTIVE CALCIUM-TRANSPORT IN RATS- ARE THEY FUNCTIONALLY RELATED

The effects of calcitriol and a novel calcitriol analogue, 22-oxacalci triol (OCT) on duodenal Ca transport, calbindin-D9k mRNA, and calbindi n-D9k content were studied in two animal models reflecting common huma n pathologies, namely arterial hypertension and chronic renal failure, as wel as in normal rats. The hormone or its analogue were administer ed intraperitoneally to vitamin-D-replete rats. Active Ca transport wa s increased in both spontaneously hypertensive rats (SHR) and in normo tensive control WKY rats 5 h after calcitriol dosing of either 60 and 600 ng per rat. In WKY, calbindin-D9k content was slightly increased a fter the injection of 60 ng calcitriol, but not of 600 ng calcitriol w hereas calbindin-D9k mRNA stayed essentially unchanged. In contrast, a ctive 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 tr eatment at same dosage led to a similar stimulation of calbindin-D9k a nd calbindin-D9k mRNA, but failed to induce an increase in active Ca t ransport. These results show that the stimulation of intestinal active Ca transport and calbindin-D9k can be entirely dissociated at the pro tein synthesis and the mRNA expression level (1) after calcitriol admi nistration to normal and hypertensive rats, and (2) after OCT administ ration to uraemic rats. Even though calbindin may play a significant r ole in the regulation of Ca translocation across the enterocyte, our w ork provides evidence that intestinal active Ca transport can be enhan ced independently of changes in calbindin-D9k and vice-versa, at least under the present non-steady-state conditions.