Regulation of extracellular calcium sensing in rat osteoclasts by femtomolar calcitonin concentrations
Certain eukaryotic cells can sense changes in their extracellular Ca2+ concentration through molecular structures termed Ca2+sensing receptors (CaRs). We have shown recently that in the bone-resorbing osteoclast, a unique cell surface-expressed ryanodine receptor (RyR), functions as the CaR. The pre...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
1996
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| _version_ | 1797104105485762560 |
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| author | Zaidi, M Shankar, V Adebanjo, O Anthony Lai, R Pazianas, M Sunavala, G Spielman, A Rifkin, B |
| author_facet | Zaidi, M Shankar, V Adebanjo, O Anthony Lai, R Pazianas, M Sunavala, G Spielman, A Rifkin, B |
| author_sort | Zaidi, M |
| collection | OXFORD |
| description | Certain eukaryotic cells can sense changes in their extracellular Ca2+ concentration through molecular structures termed Ca2+sensing receptors (CaRs). We have shown recently that in the bone-resorbing osteoclast, a unique cell surface-expressed ryanodine receptor (RyR), functions as the CaR. The present study demonstrates that the sensitivity of this receptor is modulated by physiological femtomolar concentrations of the bone-conserving hormone, calcitonin. Calcitonin was found to inhibit cytosolic Ca2+ responses to both Ca2+ and Ni2+. The latter inhibition was mimicked by amylin (10-12 M), calcitonin gene-related peptide (10-12 M), cholera toxin (5 μg/l), and dibutyryl adenosine 3′, 5′-cyclicmonophosphate (cAMP) (2.5 × 10-4 or 5 × 10-4 M) and was reversed by the protein kinase A phosphorylation inhibitor, IP-20. Finally, using a quench flow module, we showed that cellular cAMP levels rise to a peak within 25 ms of calcitonin application; this is consistent with the peptide's rapid effect on CaR activation. We conclude, therefore, that cAMP plays a critical role in the control of CaR function by calcitonin. calcium ion channel; bone resorption; osteoporosis; ryanodine receptor. |
| first_indexed | 2024-03-07T06:29:07Z |
| format | Journal article |
| id | oxford-uuid:f55affc2-bdba-4b7c-9908-292fc1e3396a |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:29:07Z |
| publishDate | 1996 |
| record_format | dspace |
| spelling | oxford-uuid:f55affc2-bdba-4b7c-9908-292fc1e3396a2022-03-27T12:26:46ZRegulation of extracellular calcium sensing in rat osteoclasts by femtomolar calcitonin concentrationsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f55affc2-bdba-4b7c-9908-292fc1e3396aEnglishSymplectic Elements at Oxford1996Zaidi, MShankar, VAdebanjo, OAnthony Lai, RPazianas, MSunavala, GSpielman, ARifkin, BCertain eukaryotic cells can sense changes in their extracellular Ca2+ concentration through molecular structures termed Ca2+sensing receptors (CaRs). We have shown recently that in the bone-resorbing osteoclast, a unique cell surface-expressed ryanodine receptor (RyR), functions as the CaR. The present study demonstrates that the sensitivity of this receptor is modulated by physiological femtomolar concentrations of the bone-conserving hormone, calcitonin. Calcitonin was found to inhibit cytosolic Ca2+ responses to both Ca2+ and Ni2+. The latter inhibition was mimicked by amylin (10-12 M), calcitonin gene-related peptide (10-12 M), cholera toxin (5 μg/l), and dibutyryl adenosine 3′, 5′-cyclicmonophosphate (cAMP) (2.5 × 10-4 or 5 × 10-4 M) and was reversed by the protein kinase A phosphorylation inhibitor, IP-20. Finally, using a quench flow module, we showed that cellular cAMP levels rise to a peak within 25 ms of calcitonin application; this is consistent with the peptide's rapid effect on CaR activation. We conclude, therefore, that cAMP plays a critical role in the control of CaR function by calcitonin. calcium ion channel; bone resorption; osteoporosis; ryanodine receptor. |
| spellingShingle | Zaidi, M Shankar, V Adebanjo, O Anthony Lai, R Pazianas, M Sunavala, G Spielman, A Rifkin, B Regulation of extracellular calcium sensing in rat osteoclasts by femtomolar calcitonin concentrations |
| title | Regulation of extracellular calcium sensing in rat osteoclasts by femtomolar calcitonin concentrations |
| title_full | Regulation of extracellular calcium sensing in rat osteoclasts by femtomolar calcitonin concentrations |
| title_fullStr | Regulation of extracellular calcium sensing in rat osteoclasts by femtomolar calcitonin concentrations |
| title_full_unstemmed | Regulation of extracellular calcium sensing in rat osteoclasts by femtomolar calcitonin concentrations |
| title_short | Regulation of extracellular calcium sensing in rat osteoclasts by femtomolar calcitonin concentrations |
| title_sort | regulation of extracellular calcium sensing in rat osteoclasts by femtomolar calcitonin concentrations |
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