부산대학교 도서관

1[alpha],25[(OH).sub.2] vitamin D3 [1,25[(OH).sub.2][D.sub.3]] increases serum [Ca.sup.2+] concentration in vivo, an action counteracted by activation of the [Ca.sup.2+]-sensing receptor (CaSR), which decreases parathyroid hormone (PTH) secretion and increases renal [Ca.sup.2+] excretion. Relatively little is known of the role the CaSR plays in this response through its potentially direct actions in kidney, gut, and bone independently of PTH. We report PTH-independent roles of the CaSR in modulating the response to exogenous 1,25[(OH).sub.2][D.sub.3] in mice with targeted disruption of both the CaSR and PTH genes ([C.sup.-][P.sup.-]) compared with that in mice with disruption of the PTH gene alone ([C.sup.+][P.sup.-]) or wild-type mice ([C.sup.+][P.sup.+]). After intraperitoneal injection of 0.5 ng/g body wt 1,25[(OH).sub.2][D.sub.3], peak calcemic responses were observed at 24 h in all three genotypes in association with 1) a greater increase in serum [Ca.sup.2+] in [C.sup.-][P.sup.-] mice than in the other genotypes on a [Ca.sup.2+]-replete diet that was attenuated by a [Ca.sup.2+]-deficient diet and pamidronate, 2) increased urinary [Ca.sup.2+]-to-creatinine ratios (UCa/Cr) in the [C.sup.+][P.sup.-] and [C.sup.+][P.sup.+] mice but a lowered ratio in the [C.sup.-][P.sup.-] mice on a [Ca.sup.2+]-replete diet, and 3) no increase in calcitonin (CT) secretion in the [C.sup.+][P.sup.+] and [C.sup.+][P.sup.-] mice and a small increase in the [C.sup.-][P.sup.-] mice. PTH deficiency had the anticipated effects on the expression of key genes involved in [Ca.sup.2+] transport at baseline in the duodenum and kidney, and injection of 1,25[(OH).sub.2][D.sub.3] increased gene expression 8 h later. However, the changes in the genes evaluated did not fully explain the differences in serum [Ca.sup.2+] seen among the genotypes. In conclusion, mice lacking the full-length CaSR have increased sensitivity to the calcemic action of 1,25[(OH).sub.2][D.sub.3] in the setting of PTH deficiency. This is principally from enhanced 1,25[(OH).sub.2][D.sub.3]-mediated gut [Ca.sup.2+] absorption and decreased renal [Ca.sup.2+] excretion, without any differences in bone-related release of [Ca.sup.2+] or CT secretion among the three genotypes that could explain the differences in their calcemic responses. vitamin D; kidney