Calcium receptor-mediated intracellular signalling

Ward, Donald T.

doi:10.1016/j.ceca.2003.10.017

Cited by 145 publications

(118 citation statements)

References 74 publications

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“…As a prototypical GPCR, signaling is initiated by activation of heterotrimeric G-proteins. The CaR has been shown to couple to G␣ i/0 and G␣ q/11 , and some data suggest that it may also interact with G␣ 12/13 (1,16,17). The signaling events put in motion by these G-proteins are complex and appear to vary considerably from one cell type to another.…”

mentioning

confidence: 99%

“…This, in turn, is associated with the initiation of MAPK cascades, including the extracellular signal-regulated kinases (ERK) 1 and 2, p38, and the stress-activated, c-Jun N-terminal kinase (JNK) (16,18,19). Activation of ERK1 and -2 through a PLC, intracellular calcium transient, protein kinase C (PKC) pathway has been suggested to be important for CaR-mediated suppression of PTH secretion in dispersed parathyroid cells (16,18,19). Activation of the CaR also decreases cAMP concentrations in these cells through a G␣ i -mediated mechanism, although this has been thought to be of secondary importance for regulating PTH secretion (16,17).…”

mentioning

confidence: 99%

“…Activation of ERK1 and -2 through a PLC, intracellular calcium transient, protein kinase C (PKC) pathway has been suggested to be important for CaR-mediated suppression of PTH secretion in dispersed parathyroid cells (16,18,19). Activation of the CaR also decreases cAMP concentrations in these cells through a G␣ i -mediated mechanism, although this has been thought to be of secondary importance for regulating PTH secretion (16,17). In other cell types, MAPK activation downstream of the CaR appears to be independent of PLC and/or PKC (20 -22).…”

mentioning

confidence: 99%

“…The signaling events put in motion by these G-proteins are complex and appear to vary considerably from one cell type to another. In parathyroid cells and in HEK cells transfected with the CaR, coupling to G␣ i/0 and/or G␣ q/11 is associated with activation of phospholipase C (PLC) and the generation of IP 3 and intracellular calcium transients (1,16,17). This, in turn, is associated with the initiation of MAPK cascades, including the extracellular signal-regulated kinases (ERK) 1 and 2, p38, and the stress-activated, c-Jun N-terminal kinase (JNK) (16,18,19).…”

mentioning

confidence: 99%

“…In parathyroid cells and in HEK cells transfected with the CaR, coupling to G␣ i/0 and/or G␣ q/11 is associated with activation of phospholipase C (PLC) and the generation of IP 3 and intracellular calcium transients (1,16,17). This, in turn, is associated with the initiation of MAPK cascades, including the extracellular signal-regulated kinases (ERK) 1 and 2, p38, and the stress-activated, c-Jun N-terminal kinase (JNK) (16,18,19). Activation of ERK1 and -2 through a PLC, intracellular calcium transient, protein kinase C (PKC) pathway has been suggested to be important for CaR-mediated suppression of PTH secretion in dispersed parathyroid cells (16,18,19).…”

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confidence: 99%

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Switching of G-protein Usage by the Calcium-sensing Receptor Reverses Its Effect on Parathyroid Hormone-related Protein Secretion in Normal Versus Malignant Breast Cells

Mamillapalli

VanHouten

Zawalich

et al. 2008

Journal of Biological Chemistry

129

113

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The calcium-sensing receptor (CaR) is a G-protein-coupled receptor that signals in response to extracellular calcium and regulates parathyroid hormone secretion. The CaR is also expressed on normal mammary epithelial cells (MMECs), where it has been shown to inhibit secretion of parathyroid hormone-related protein (PTHrP) and participate in the regulation of calcium and bone metabolism during lactation. In contrast to normal breast cells, the CaR has been reported to stimulate PTHrP production by breast cancer cells. In this study, we confirmed

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confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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Switching of G-protein Usage by the Calcium-sensing Receptor Reverses Its Effect on Parathyroid Hormone-related Protein Secretion in Normal Versus Malignant Breast Cells

Mamillapalli

VanHouten

Zawalich

et al. 2008

Journal of Biological Chemistry

129

113

View full text Add to dashboard Cite

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Calcium‐sensing receptor (CaSR) as a novel target for ischemic neuroprotection

Kim

et al. 2014

Ann Clin Transl Neurol

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ObjectIschemic brain injury is the leading cause for death and long-term disability in patients who suffer cardiac arrest and embolic stroke. Excitotoxicity and subsequent Ca2+-overload lead to ischemic neuron death. We explore a novel mechanism concerning the role of the excitatory extracellular calcium-sensing receptor (CaSR) in the induction of ischemic brain injury.MethodMice were exposed to forebrain ischemia and the actions of CaSR were determined after its genes were ablated specifically in hippocampal neurons or its activities were inhibited pharmacologically. Since the CaSR forms a heteromeric complex with the inhibitory type B γ-aminobutyric acid receptor 1 (GABABR1), we compared neuronal responses to ischemia in mice deficient in CaSR, GABABR1, or both, and in mice injected locally or systemically with a specific CaSR antagonist (or calcilytic) in the presence or absence of a GABABR1 agonist (baclofen).ResultsBoth global and focal brain ischemia led to CaSR overexpression and GABABR1 downregulation in injured neurons. Genetic ablation of Casr genes or blocking CaSR activities by calcilytics rendered robust neuroprotection and preserved learning and memory functions in ischemic mice, partly by restoring GABABR1 expression. Concurrent ablation of Gabbr1 gene blocked the neuroprotection caused by the Casr gene knockout. Coinjection of calcilytics with baclofen synergistically enhanced neuroprotection. This combined therapy remained robust when given 6 h after ischemia.InterpretationOur study demonstrates a novel receptor interaction, which contributes to ischemic neuron death through CaSR upregulation and GABABR1 downregulation, and feasibility of neuroprotection by concurrently targeting these two receptors.

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Expression of Calcium‐Sensing Receptor in Quail Granulosa Explants: A Key to Survival During Folliculogenesis

Diez-Fraile

Mussche

Berghe

et al. 2010

The Anatomical Record

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This study investigated the potential role of the calcium-sensing receptor (CaR) in mediating survival of granulosa cells (GCs) in follicles of the Japanese quail (Coturnix coturnix japonica). Immunoreactivity of CaR was shown in GCs of quail preovulatory follicles as well as in the remnants of the GC layer after ovulation. Conversely, the CaR could not be detected by immunocytochemistry in the granulosa of smaller undifferentiated follicles. The presence of CaR in follicles destined to ovulate was confirmed by immunoblot and the receptor was identified as a protein of 115-125 kDa. Addition of different CaR agonists to granulosa explants in culture for 24 hr caused inhibition of apoptosis elicited by gonadotropin withdrawal on its own or in combination with C 8 -ceramide addition. Furthermore, R-568, a specific, positive allosteric modulator of CaR, not only inhibited apoptosis but also increased GC number per viewing field in cultured granulosa explants. This observation could be attributed not to a rise in GC proliferation but to a more compact tissue structure, including a distinct distribution pattern of connexin-43 gap junction proteins. Incubation in the presence of LY294002, a specific phosphatidylinositol-3 kinase inhibitor, increased GC apoptosis, indicating that this pathway is involved in GC survival signaling. However, LY294002-induced apoptosis was considerably attenuated by incubation with R-568, indicating that other pathways might be major contributors to the survival mediated by CaR agonists. We provide direct evidence for the presence of CaR in preovulatory granulosa explants and suggest a pivotal role for CaR in follicle selection. Anat Rec,

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Calcium receptor-mediated intracellular signalling

Cited by 145 publications

References 74 publications

Switching of G-protein Usage by the Calcium-sensing Receptor Reverses Its Effect on Parathyroid Hormone-related Protein Secretion in Normal Versus Malignant Breast Cells

Switching of G-protein Usage by the Calcium-sensing Receptor Reverses Its Effect on Parathyroid Hormone-related Protein Secretion in Normal Versus Malignant Breast Cells

Calcium‐sensing receptor (CaSR) as a novel target for ischemic neuroprotection

Expression of Calcium‐Sensing Receptor in Quail Granulosa Explants: A Key to Survival During Folliculogenesis

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