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Type: Journal article
Title: Physiological Levels of Calcitonin Regulate the Mouse Osteoclast Calcitonin Receptor by a Protein Kinase A-Mediated Mechanism
Author: Wada, S.
Udagawa, N.
Nagata, N.
Martin, T.
Findlay, D.
Citation: Endocrinology, 1996; 137(1):312-320
Publisher: The Endocrine Society
Issue Date: 1996
ISSN: 0013-7227
Abstract: We have reported that calcitonin (CT) treatment induced downregulation of the CT receptor (CTR) in mouse osteoclast-like cells (OCLs). Here, we studied the features of homologous down-regulation of the CTR in mature mouse OCLs. Treatment with salmon CT (sCT) and human CT (hCT) reduced [125I]sCT specific binding. The decreased binding after 24 h of CT treatment was associated with a decrease in the cell surface receptor concentration. The extent of CT-induced down-regulation in 24 h was dose-dependent, and the ED50 value was 3.6 +/- 4.1 (mean +/- SD; n = 3) x 10(-13 M for sCT and 4.9 +/- 3.3 x 10(-11) M for hCT. These values were very similar to those for the CT inhibition of the bone-resorbing activity of OCLs. The data suggest that these two distinct actions of CT may be mediated by a common intracellular pathway. Treatment of OCLs with activators of protein kinase A (PKA) mimicked the effect of CT on CTR downregulation, whereas neither activation of protein kinase C nor elevation of intracellular Ca2+ did so. Attenuation of CT-induced CTR down-regulation by the competitive cAMP antagonist, RpcAMP, and high concentrations of H-7, but not by protein kinase C-specific inhibitors (sphingosine, staurosporine, and a lower concentration of H-7), suggested that the PKA pathway is primarily involved in homologous regulation of the CTR. The changes in CTR messenger RNA confirm the findings in binding studies and demonstrate that CT treatment of OCLs results in decreased CTR synthesis through the PKA pathway. The low concentrations of hCT that result in CTR regulation are very close to the physiological range, providing new insights into a dynamic relationship between circulating levels of CT and CTR expression in osteoclasts.
Keywords: Cells, Cultured
Mice, Inbred C57BL
Bone Resorption
Cyclic AMP-Dependent Protein Kinases
Protein Kinase C
Receptors, Calcitonin
Oligonucleotide Probes
RNA, Messenger
Enzyme Activation
Base Sequence
Molecular Sequence Data
Calcium-Calmodulin-Dependent Protein Kinases
DOI: 10.1210/endo.137.1.8536630
Appears in Collections:Aurora harvest
Orthopaedics and Trauma publications

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