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Quarterly Journal of Experimental Physiology 73.4 pp 471-485
© The Physiological Society 1988
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EFFECTS OF PEPTIDES FROM THE CALCITONIN GENES ON BONE AND BONE CELLS

Mone Zaidi 1, Peter J. R. Bevis 1, Jeremy L. Beacham 1, Iain MacIntyre 1, Timothy J. Chambers 2, and Rose E. Gaines Das 3

1 Endocrine Unit, Department of Chemical Pathology, Royal Postgraduate Medical School, Hammersmith Hospital, Du Cane Road, London W12 OHS
2 Department of Histopathology, St George's Hospital Medical School, Cranmer Terrace, London SW17 0RE
3 National Institute for Biological Standards and Control, Potters Bar, Hertfordshire

The calcitonin-calcitonin gene-related peptide (CGRP) gene complex encodes a family of novel peptides - calcitonin, CGRP and katacalcin. Whereas calcitonin is a circulating hormone involved in skeletal maintenance, the physiological function of CGRP still remains unclear. In the present study we have compared the biological activity of CGRP with that of calcitonin using three experimental systems. We have demonstrated that both peptides inhibit bone resorption by active rat osteoclasts and thus lower plasma calcium when injected into young rats. In both respects the CGRP homologues (rat, human agr and human beta) were found to be 100- to 1000-fold less potent than human calcitonin. The effects of the CGRP peptides and calcitonin were only additive. Human CGRP (agr) also caused a marked dose-dependent elevation of bone cyclic AMP levels in mice, somewhat like calcitonin. Though from our studies it would seem reasonably clear that CGRP is weakly agonistic for the calcitonin receptor on the osteoclast to produce effects on bone resorption and plasma calcium, it is still unclear whether the elevation of bone cyclic AMP simply represents an osteoclastic effect or an additional, more important, effect on osteoblasts. It is highly unlikely that CGRP may exert systemic effects on bone. Nevertheless, the peptide may be an important local regulator of bone cell function.

Submitted on June 23, 1987
Accepted on February 8, 1988




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Am. J. Pathol., March 1, 2007; 170(3): 1018 - 1027.
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Copyright © 1988 by the The Physiological Society.