Activation of p42/44 and p38 Mitogen-Activated Protein Kinases by Extracellular Calcium-Sensing Receptor Agonists Induces Mitogenic Responses in the Mouse Osteoblastic MC3T3-E1 Cell Line

2000 ◽  
Vol 279 (2) ◽  
pp. 363-368 ◽  
Author(s):  
Toru Yamaguchi ◽  
Naibedya Chattopadhyay ◽  
Olga Kifor ◽  
Jennifer L. Sanders ◽  
Edward M. Brown
Keyword(s):  
Cell Line ◽  
Protein Kinases ◽  
Extracellular Calcium ◽  
Calcium Sensing Receptor ◽  
Mitogen Activated Protein Kinases ◽  
Receptor Agonists ◽  
Calcium Sensing ◽  
Mitogen Activated Protein

Expression of extracellular calcium-sensing receptor in human osteoblastic MG-63 cell line

2001 ◽  
Vol 280 (2) ◽  
pp. C382-C393 ◽  
Author(s):  
Toru Yamaguchi ◽  
Naibedya Chattopadhyay ◽  
Olga Kifor ◽  
Chianping Ye ◽  
Peter M. Vassilev ◽  
...  
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Northern Blot Analysis ◽  
Pcr Primers ◽  
Extracellular Calcium ◽  
Calcium Sensing Receptor ◽  
Patch Clamp Technique ◽  
Calcium Sensing ◽  
Specific Affinity

We have previously shown the expression of the extracellular calcium (Cao 2+)-sensing receptor (CaR) in osteoblast-like cell lines, and others have documented its expression in sections of murine, bovine, and rat bone. The existence of the CaR in osteoblasts remains controversial, however, since some studies have failed to document its expression in the same osteoblast-like cell lines. The goals of the present study were twofold. 1) We sought to determine whether the CaR is expressed in the human osteoblast-like cell line, MG-63, which has recently been reported by others not to express this receptor. 2) We investigated whether the CaR, if present in MG-63 cells, is functionally active, since most previous studies have not proven the role of the CaR in mediating known actions of Cao 2+ on osteoblast-like cells. We used immunocytochemistry and Western blotting with the specific, affinity-purified anti-CaR antiserum 4637 as well as Northern blot analysis and RT-PCR using a riboprobe and PCR primers specific for the human CaR, respectively, to show readily detectable CaR protein and mRNA expression in MG-63 cells. Finally, we employed the patch-clamp technique to show that an elevation in Cao 2+ as well as the specific, allosteric CaR activator NPS R-467 (0.5 μM), but not its less active stereoisomer NPS S-467 (0.5 μM), activate an outward K+ channel in MG-63 cells, strongly suggesting that the CaR in MG-63 cells is not only expressed but is functionally active.

scholarly journals Activation of the extracellular calcium-sensing receptor initiates insulin secretion from human islets of Langerhans: involvement of protein kinases

2006 ◽  
Vol 190 (3) ◽  
pp. 703-710 ◽  
Author(s):  
Elizabeth Gray ◽  
Dany Muller ◽  
Paul E Squires ◽  
Henry Asare-Anane ◽  
Guo-Cai Huang ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Protein Kinases ◽  
Islets Of Langerhans ◽  
Divalent Cations ◽  
Human Islets ◽  
Extracellular Calcium ◽  
Calcium Sensing Receptor ◽  
Calcium Calmodulin Dependent ◽  
Calcium Sensing ◽  
Pancreatic Islets Of Langerhans

The extracellular calcium-sensing receptor (CaR) is usually associated with systemic Ca2+ homeostasis, but the CaR is also expressed in many other tissues, including pancreatic islets of Langerhans. In the present study, we have used human islets and an insulin-secreting cell line (MIN6) to investigate the effects of CaR activation using the calcimimetic R-568, a CaR agonist that activates the CaR at physiological concentrations of extracellular Ca2+. CaR activation initiated a marked but transient insulin secretory response from both human islets and MIN6 cells at a sub-stimulatory concentration of glucose, and further enhanced glucose-induced insulin secretion. CaR-induced insulin secretion was reduced by inhibitors of phospholipase C or calcium–calmodulin-dependent kinases, but not by a protein kinase C inhibitor. CaR activation was also associated with an activation of p42/44 mitogen-activated protein kinases (MAPK), and CaR-induced insulin secretion was reduced by an inhibitor of p42/44 MAPK activation. We suggest that the β-cell CaR is activated by divalent cations co-released with insulin, and that this may be an important mechanism of intra-islet communication between β-cells.

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