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Studies on the mechanisms by which 2-chloroadenosine stimulates bone resorption in tissue culture.

Abstract
The effect of 2-chloroadenosine on bone resorption was studied in calvarial bones from 6-7-day-old mice in organ culture. 2-Chloroadenosine stimulated the mobilization of minerals (40Ca, 45Ca) and increased the degradation of matrix ([3H]proline) from the bones. The nucleoside also caused an increased release of beta-glucuronidase, a lysosomal enzyme. In doses above 30 microM 2-chloroadenosine was cytotoxic, as evidenced by an increased release of lactate dehydrogenase. 2-Chloroadenosine-stimulated resorption could be inhibited by calcitonin, increased concentration of phosphate in culture medium, cortisone, dexamethasone, indomethacin, naproxen, meclofenamic acid and 5,8,11,14-eicosatetraynoic acid. 2-Chloroadenosine was much more sensitive to inhibition by dexamethasone than was parathyroid hormone. The response to the maximal dose of 2-chloroadenosine could not be enhanced by parathyroid hormone, 1 alpha-hydroxyvitamin D-3 and prostaglandin E2. An exposure to 2-chloroadenosine for 12 h was not sufficient to produce prolonged resorption. The results suggest that 2-chloroadenosine stimulated bone resorption by a process which is dependent on osteoclastic activity. The possibility that the effect of 2-chloroadenosine, either directly or indirectly, is related to formation of prostaglandins is discussed in the light of the above data.
AuthorsU Lerner, B B Fredholm
JournalBiochimica et biophysica acta (Biochim Biophys Acta) Vol. 757 Issue 2 Pg. 226-34 (May 25 1983) ISSN: 0006-3002 [Print] Netherlands
PMID6405798 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Arachidonic Acids
  • Parathyroid Hormone
  • Prostaglandins E
  • 2-Chloroadenosine
  • Arachidonic Acid
  • Glucuronidase
  • Calcitriol
  • Adenosine
  • Dinoprostone
  • Calcium
Topics
  • 2-Chloroadenosine
  • Adenosine (analogs & derivatives, pharmacology)
  • Animals
  • Arachidonic Acid
  • Arachidonic Acids (metabolism)
  • Bone Resorption (drug effects)
  • Bone and Bones (metabolism)
  • Calcitriol (pharmacology)
  • Calcium (metabolism)
  • Cell Survival (drug effects)
  • Culture Techniques
  • Dinoprostone
  • Glucuronidase (metabolism)
  • Mice
  • Parathyroid Hormone (pharmacology)
  • Prostaglandins E (pharmacology)

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