Effects of aluminum on the parathyroid-hormone receptors of bone and kidney

Pun, K. K., Ho, P. W. M. and Lau, P. (1990) Effects of aluminum on the parathyroid-hormone receptors of bone and kidney. Kidney International, 37 1: 72-78. doi:10.1038/ki.1990.10

Author Pun, K. K.
Ho, P. W. M.
Lau, P.
Title Effects of aluminum on the parathyroid-hormone receptors of bone and kidney
Journal name Kidney International   Check publisher's open access policy
ISSN 0085-2538
Publication date 1990-01
Sub-type Article (original research)
DOI 10.1038/ki.1990.10
Volume 37
Issue 1
Start page 72
End page 78
Total pages 7
Place of publication New York, USA
Publisher Nature Publishing Group
Language eng
Subject 110306 Endocrinology
Abstract Effects of aluminum on the parathyroid hormone receptors of bone and kidney. Aluminum intoxication is associated with low osseous remodeling rate and peripheral resistance to parathyroid hormone (PTH). The pathophysiological mechanism of these aluminum induced changes was investigated using cultured clonal osteoblastic UMR-106 cells as well as dog renal cortical membrane. Both systems possess high-affinity PTH receptors that are coupled to adenylate cyclase. The UMR-106 cells have typical osteoblastic features, including receptors for the tissue-specific hormones, formation and mineralization of a bone-like ground substance and exclusive synthesis of type 1 collagen. The results show that aluminum at a concentration of 4 microM and 40 microM significantly inhibits the cyclic AMP responses to PTH challenge in UMR-106 cells, and this is associated with significant decrease in the binding to the PTH receptor. At 200 microM no PTH-responsive adenylate cyclase or binding to receptor can be demonstrated. The effect of aluminum on UMR-106 rat osteosarcoma cells is not due to changes in cell number, cell viability or rate of mitogenesis. Similar results are obtained with dog kidney membrane. At a concentration of 10 microM and 400 microM there is significant inhibition of the binding of PTH to kidney membrane and proportional decrease in PTH-stimulated adenylate cyclase. With higher concentration of aluminum, no response or binding can be demonstrated. In conclusion, aluminum at concentrations of 4 to 400 microM is associated with a decrease in affinity of PTH receptor and concomitant suppression of PTH-stimulated adenylate cyclase. The two processes are affected to a similar degree by different concentrations of aluminum, and it is likely that the primary effect of aluminum is on the affinity of the receptor which may be related to exchange of aluminum with magnesium at G-protein. This effect could account for the observed peripheral resistance to PTH in aluminum intoxication as well as the suppression of osseous remodeling rate in these patients.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
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Created: Mon, 19 Jul 2010, 15:01:55 EST by Laura McTaggart on behalf of Institute for Molecular Bioscience