Regulation of extracellular calcium-sensing in rat osteoclasts by
femtomolar calcitonin concentrations.
Zaidi, Mone, Vijai S. Shankar, Olugbenga A. Adebanjo, F. Anthony Lai,
Michael Pazianas, Gulshan Sunavala, Andrew I. Spielman, and Barry R.
Rifkin.
Department of Internal Medicine, University of Arkansas for Medical
Sciences and GRECC at the VA Medical Center, Little Rock, AR 72205,
USA; National Institute for Medical Research, Medical Research
Council, Mill Hill, London, NW7 1AA, UK; St. George's Hospital
Medical School, London, U.K.; New York University College of
Dentistry, New York 10010, USA
APStracts 3:0098F, 1996.
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 (CGRP, 10-12 M), cholera
toxin (5 mg l-1) and dibutyryl cyclic AMP (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
cyclic AMP levels rise to a peak within 25 milliseconds of calcitonin
application; this is consistent with the peptide's rapid effect on
CaR activation. We conclude therefore that cyclic AMP plays a
critical role in the control of CaR function by calcitonin.
Received 1 March 1996; accepted in final form 10 May 1996.
APS Manuscript Number F73-6.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 June 96