Regulation of Calcium Homeostasis

Regulation of Calcium Homeostasis Calcium homeostasis necessitates the maintenance of a dynamic equilibrium of calcium fluxes between three different compartments which harbor the mineral ion in vastly different concentrations. Thus, homeostatic control mechanisms ought to modulate calcium fluxes between different body compartments in a way which allows the generation and maintenance of steep concentration gradients between the skeletal tissue, the extracellular fluid and the intracellular - that is, the cytoplasmic compartment. Of particular importance thereby is the rigid control of plasma free Ca , because even small deviations from the normal level induce profound changes in both intracellular free Ca, as well as in the amount of calcium deposited at skeletal sites, inevitably causing adverse effects on bone health (cf. Whedon 1980). 

Calcium homeostasis is primarily achieved by the action of a number of hormones on calcium fluxes across the intestinal and renal tubular epithelium, as well as to and from bone (Arnaud 1978). Of particular importance are the respective cellular actions of the steroid hormone 1,25-dihy-droxyvitamin D3 (1,25 (OH)2D3), the biologically active metabolite of vitamin D3 (see 

An important contribution to systemic Ca homeostasis comes from the extracellular calcium-sensing receptor (CaR) (Mithal and Brown 2003). The CaR is a G protein-coupled plasma membrane receptor, by which minute variations in [Ca +] are transduced into changes in cellular functions, including proliferative activity. The CaR is expressed not only in the parathyroid gland (Brown et al. 1993), but importantly also on cells of the main calcium-regulating organs, such as bone (Yamaguchi et al. 

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In addition to its classical role as regulator of calcium homeostasis, 1,25-dihydroxy vitamin D3 (calcitriol) displays immunosuppressive properties. Inhibition of T-lymphocyte proliferation seems to be mediated via regulation of CD80/86 costimulatory molecule expression on APCs. For clinical use as immunosuppressant, however, analogues of vitamin D3 that do not influence calcium metabolism are needed. 

Oram S, Cai X, Haleem R, Cyriac J, Wang Z. 2006. Regulation of calcium homeostasis by S100RVP, an androgen-regulated SI00 protein in the rat ventral prostate. Prostate 66(7) 768-778. 

Parathyroid hormone (PTH) is an 84-amino acid polypeptide hormone that mediates bone remodeling and is an essential regulator of calcium homeostasis. Prolonged exposure to PTH changes the phenotype of the osteoblast from a cell involved in bone formation to one directing bone... 

Figure 30-5. Regulation of calcium homeostasis by the combined action of 1,25-dihydroxy vi ta m in D and parathyroid hormone (PTH). ECF, extracellular fluid.

VDR is a receptor of 1,25-dihydroxyvitamin D3 (DHD3 31), which is an active form of vitamin D and plays critical roles in a variety of biological activities, including regulation of calcium homeostasis, bone mineralization and control of cellular growth, differentiation, and apoptosis. VDR antagonists can be expected... 

The significance of the enzyme is due to the pleiotropic actions of the active form of vitamin D, la,25-dihydroxyvitamin Dj, which include regulation of calcium homeostasis, control of bone cell differentiation, and modification of immune responses. The la-hydroxylation reaction is rate limiting and hormonally controlled. The expression of the gene is usually tightly regulated (yide supra), but gene defects are... 

Martin S, Giannone G, Andriantsitohaina R, Martinez MC (2003b) Delphinidin, an active compound of red wine, inhibits endotheUal cell apoptosis via nitric oxide pathway and regulation of calcium homeostasis. Br J Pharmacol 139 1095-1102... 

The concentration of ionized calcium in serum is closely regulated because it has profound effects on the function of nerves and muscles, blood clotting, and hormone secretion. The principal regulators of calcium homeostasis in humans and most terrestrial vertebrates are PTH and the active form of vitamin D, 1,25(0H)2 vitamin D3 (Figure 2). 

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