An Overview of Extracellular Calcium Homeostasis and the Roles of the CaR in Parathyroid and C-cells

Roles of Ca2+ and the Ca2+‐sensing receptor (CASR) in the expression of inducible NOS (nitric oxide synthase)‐2 and its BH4 (tetrahydrobiopterin)‐dependent activation in cytokine‐stimulated adult human astrocytes

“…However, Li et al [2003] have also reported that an agent such as ATP that triggers a cytosolic Ca 2þ surge in murine astrocytes also induces NO synthesis. The responsiveness of NOS-2 induction and NO production by our normal human astrocytes to changes in the medium's Ca 2þ concentration from 0.75 to 1.8 mM is characteristic of processes driven by a cation sensor like the one used by parathyroid chief cells with its 1.0-1.3 mM set-point for maximizing the signal:noise ratio to detect changes in the high ionic Ca 2þ concentration in the blood [Mithal and Brown, 2003]. And indeed the higher extracellular Ca 2þ concentration needed by the confluent adult cells to express NOS-2 coincided with an increased expression of a parathyroid-like CASR like that found in normal fetal human astrocytes by Chattopadhyay et al [2000] and Chattopadhyay and Brown [2003].…”

Parathyroid hormone (PTH) and hematopoiesis: New support for some old observations

“…Then Rixon and Whitfield [1969] showed that one intraperitoneal injection of enough Na-caseinate to halve the circulating free Ca 2þ concentration in female CF 1 mice doubled the proliferation of femoral bone marrow cells and tripled the pro- [Nemeth et al, 2001;Mithal and Brown, 2003]. If there is sufficient circulating Ca 2þ the CASR signaling restrains the release of PTH, but if the receptors are directly silenced by a ''calcilytic'' inhibitor [Nemeth et al, 2001] or by reducing the circulating free Ca 2þ concentration with a chelator such as EDTA, the CASR signaling is reduced and the restraints on parathyroid release are lifted.…”

“…So it was necessary to use the animals' own endogenous PTH. This was done by lowering the circulating free (ionic) Ca 2þ concentration by injecting the Ca 2þ -chelating EDTA or the Ca 2þ -binding Na-caseinate, either of which would trigger the release of PTH from parathyroid chief cells by silencing the cells' secretion-suppressing CASRs (Ca 2þ -sensing receptors) [Mithal and Brown, 2003] (Fig. 1).…”

Calcium

“…It should be noted that, in addition, a number of biologically active peptides such as calcitonin (Copp 1979), cytokines, and growth factors (Canalis 1993) as well as prostaglandins (Raisz 1990) are involved in local regulation of calcium metabolism, particularly in osseous tissue. An important contribution to systemic Ca 2+ 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 2+ ] o are transduced into changes in cellular functions, including proliferative activity.…”