Regulation of extracellular calcium sensing in rat osteoclasts by femtomolar calcitonin concentrations

Mone Zaidi, Vijai S. Shankar, Olugbenga A. Adebanjo, R. Anthony Lai, Michael Pazianas, Gulshan Sunavala, Andrew Spielman, Barry R. Rifkin

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
JournalThe American journal of physiology
Volume271
Issue number3 PART 2
StatePublished - 1996

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Calcitonin
Osteoclasts
Calcium
Ryanodine Receptor Calcium Release Channel
Islet Amyloid Polypeptide
Calcium-Sensing Receptors
Bone and Bones
Calcitonin Gene-Related Peptide
Cholera Toxin
Eukaryotic Cells
Calcium Channels
Bone Resorption
Cyclic AMP-Dependent Protein Kinases
Molecular Structure
Adenosine
Osteoporosis
Phosphorylation
Hormones
Peptides

ASJC Scopus subject areas

  • Physiology (medical)
  • Physiology

Cite this

Zaidi, M., Shankar, V. S., Adebanjo, O. A., Anthony Lai, R., Pazianas, M., Sunavala, G., ... Rifkin, B. R. (1996). Regulation of extracellular calcium sensing in rat osteoclasts by femtomolar calcitonin concentrations. The American journal of physiology, 271(3 PART 2).

Regulation of extracellular calcium sensing in rat osteoclasts by femtomolar calcitonin concentrations. / Zaidi, Mone; Shankar, Vijai S.; Adebanjo, Olugbenga A.; Anthony Lai, R.; Pazianas, Michael; Sunavala, Gulshan; Spielman, Andrew; Rifkin, Barry R.

In: The American journal of physiology, Vol. 271, No. 3 PART 2, 1996.

Research output: Contribution to journalArticle

Zaidi, M, Shankar, VS, Adebanjo, OA, Anthony Lai, R, Pazianas, M, Sunavala, G, Spielman, A & Rifkin, BR 1996, 'Regulation of extracellular calcium sensing in rat osteoclasts by femtomolar calcitonin concentrations', The American journal of physiology, vol. 271, no. 3 PART 2.
Zaidi M, Shankar VS, Adebanjo OA, Anthony Lai R, Pazianas M, Sunavala G et al. Regulation of extracellular calcium sensing in rat osteoclasts by femtomolar calcitonin concentrations. The American journal of physiology. 1996;271(3 PART 2).
Zaidi, Mone ; Shankar, Vijai S. ; Adebanjo, Olugbenga A. ; Anthony Lai, R. ; Pazianas, Michael ; Sunavala, Gulshan ; Spielman, Andrew ; Rifkin, Barry R. / Regulation of extracellular calcium sensing in rat osteoclasts by femtomolar calcitonin concentrations. In: The American journal of physiology. 1996 ; Vol. 271, No. 3 PART 2.
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