TY - JOUR
T1 - Regulation of extracellular calcium sensing in rat osteoclasts by femtomolar calcitonin concentrations
AU - Zaidi, Mone
AU - Shankar, Vijai S.
AU - Adebanjo, Olugbenga A.
AU - Anthony Lai, R.
AU - Pazianas, Michael
AU - Sunavala, Gulshan
AU - Spielman, Andrew I.
AU - Rifkin, Barry R.
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 1996
Y1 - 1996
N2 - 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.
AB - 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.
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U2 - 10.1152/ajprenal.1996.271.3.f637
DO - 10.1152/ajprenal.1996.271.3.f637
M3 - Article
C2 - 8853426
AN - SCOPUS:0029817175
SN - 0002-9513
VL - 271
SP - F637-F644
JO - American Journal of Physiology
JF - American Journal of Physiology
IS - 3 PART 2
ER -