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 Ca(2+)-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 micrograms/l) and dibutyryl adenosine 3',5'-cyclic monophosphate (cAMP) (2.5 x 10(-4) or 5 x 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.
Zaidi
M
M
Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, USA.
Shankar
V S
VS
Adebanjo
O A
OA
Lai
F A
FA
Pazianas
M
M
Sunavala
G
G
Spielman
A I
AI
Rifkin
B R
BR
D000818:Animals; D002116:Calcitonin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002135:Calcium-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism*; D009532:Nickel / Q000494:pharmacology; D009994:Osmolar Concentration; D010010:Osteoclasts / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D002121:Calcium Channel Blockers; D002135:Calcium-Binding Proteins; D009532:Nickel; D002116:Calcitonin; D000242:Cyclic AMP; D002118:Calcium